Trial Outcomes & Findings for Free Fatty Acids-Induced Hypertension in Obese Subjects (Aim #2) (NCT NCT02406586)

Results Overview

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 4 hours during Intralipid infusion.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

36 participants

Primary outcome timeframe

Pre-dose (Baseline), within 4 hours at Baseline visit

Results posted on

2019-01-08

Participant Flow

Subjects recruited from July 2009 to January 2011 at Grady Memorial Hospital.

All subjects will receive IV Intralipid (20% solution at 20 ml/hour) prior to randomization.

Participant milestones

Participant milestones
Measure	Salsalate Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Overall Study STARTED	12	12	12
Overall Study COMPLETED	11	8	10
Overall Study NOT COMPLETED	1	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Salsalate Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Overall Study Lost to Follow-up	0	4	2
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

Free Fatty Acids-Induced Hypertension in Obese Subjects (Aim #2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.	Total n=35 Participants Total of all reporting groups
Age, Continuous	34 years STANDARD_DEVIATION 11 • n=39 Participants	41 years STANDARD_DEVIATION 11 • n=41 Participants	37.5 years STANDARD_DEVIATION 8 • n=35 Participants	37.5 years STANDARD_DEVIATION 10 • n=31 Participants
Sex: Female, Male Female	7 Participants n=39 Participants	6 Participants n=41 Participants	2 Participants n=35 Participants	15 Participants n=31 Participants
Sex: Female, Male Male	4 Participants n=39 Participants	6 Participants n=41 Participants	10 Participants n=35 Participants	20 Participants n=31 Participants

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 4 hours at Baseline visit

Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 4 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure.	15.37 mmHg Standard Deviation 9.15	10.04 mmHg Standard Deviation 8.72	10.25 mmHg Standard Deviation 12.83

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 8 hours at Baseline visit

Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. from Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 8 hours during Intralipid.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	13.02 mmHg Standard Deviation 16.42	2.03 mmHg Standard Deviation 11.27	5.47 mmHg Standard Deviation 16.81

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 12 hours at Baseline visit

Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	20.55 mmHg Standard Deviation 10.06	1.74 mmHg Standard Deviation 10.59	5.25 mmHg Standard Deviation 15.64

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 16 hours at Baseline visit

Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 16 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	15.78 mmHg Standard Deviation 13.12	8.05 mmHg Standard Deviation 9.35	3.6 mmHg Standard Deviation 13.34

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 20 hours at Baseline visit

Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 20 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	13.27 mmHg Standard Deviation 9.84	9.39 mmHg Standard Deviation 8.36	11.4 mmHg Standard Deviation 12.70

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 24 hours at Baseline visit

Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	13.93 mmHg Standard Deviation 13.90	13.21 mmHg Standard Deviation 11.64	10.27 mmHg Standard Deviation 9.38

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 4 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 4 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	11.50 mmHg Standard Deviation 10.54	14.32 mmHg Standard Deviation 8.92	4.26 mmHg Standard Deviation 13.99

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 8 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure from at Week 6 from pre-dosing with Intralipid to 8 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	10.1 mmHg Standard Deviation 11.62	11.62 mmHg Standard Deviation 16.15	4.14 mmHg Standard Deviation 10.43

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 12 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	9.50 mmHg Standard Deviation 13.46	8.14 mmHg Standard Deviation 15.34	0.38 mmHg Standard Deviation 14.13

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 16 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 16 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	7.85 mmHg Standard Deviation 12.60	7.55 mmHg Standard Deviation 8.78	-0.04 mmHg Standard Deviation 6.69

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 20 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 20 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	12.88 mmHg Standard Deviation 12.84	8.84 mmHg Standard Deviation 12.25	6.6 mmHg Standard Deviation 9.28

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 24 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

Systolic blood pressure is the amount of pressure the heart generates when pumping blood through the arteries to the body. Current guidelines identify normal systolic blood pressure as lower than 120 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 24-hour infusion with subjects in supine position. Change is the difference in systolic blood pressure at Week 6 from pre-dosing with Intralipid to 24 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Systolic Blood Pressure	11.23 mmHg Standard Deviation 9.56	9.92 mmHg Standard Deviation 7.42	3.04 mmHg Standard Deviation 9.41

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 12 hours at Baseline visit

Population: One subject in the salsalate arm withdrew from the study was not included in the baseline analysis population.

The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Flow-mediated Dilation	0.14 percent change in diameter Standard Deviation 0.27	0.24 percent change in diameter Standard Deviation 0.22	0.26 percent change in diameter Standard Deviation 0.34

PRIMARY outcome

Timeframe: Pre-dose (Baseline), within 24 hours at Baseline visit

Population: One subject on the salsalate arm withdrew from the study was not included in the baseline analysis population.

The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the baseline visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=12 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Flow-mediated Dilation	0.35 percent change in diameter Standard Deviation 0.29	0.53 percent change in diameter Standard Deviation 0.47	0.47 percent change in diameter Standard Deviation 0.45

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 12 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 12 hours during Intralipid infusion.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=7 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=10 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Flow-mediated Dilation	0.22 percent change in diameter Standard Deviation 0.27	0.42 percent change in diameter Standard Deviation 0.43	0.20 percent change in diameter Standard Deviation 0.26

PRIMARY outcome

Timeframe: Pre-dose (Week 6), within 24 hours at Week 6 visit

Population: 7 subjects withdrew from the study prior to the Week 6 visit. Data was also not collected for one additional subject.

The change in endothelium-dependent vascular reactivity will be measured by flow-mediated dilation (FMD) of the brachial artery using a high-resolution vascular ultrasound with a 10-MHz linear array transducer. FMD is expressed as the percentage increase in diameter at the Week 6 visit from pre-dosing with Intralipid to 24 hours during Intralipid infusion

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=7 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=10 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Flow-mediated Dilation	0.39 percent change in diameter Standard Deviation 0.28	0.70 percent change in diameter Standard Deviation 0.52	0.48 percent change in diameter Standard Deviation 0.29

SECONDARY outcome

Timeframe: Baseline, 6 weeks

Population: 6 subjects were lost to follow up, 1 withdrew from the study, and data was not collected for 1 additional subject

Diastolic blood pressure is the amount of pressure in the arteries when the heart is at rest between beats. Current guidelines identify normal diastolic blood pressure as lower than 80 mmHg. Blood pressure was measured in triplicate with a manual cuff prior to and every 4 hours during the 8 hour infusion with subjects in supine position. Change is the difference between 6-week diastolic blood pressure from baseline diastolic blood pressure.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Diastolic Blood Pressure From Baseline to 6 Weeks	1.00 mmHg Standard Deviation 10.13	-1.50 mmHg Standard Deviation 6.93	2.22 mmHg Standard Deviation 10.49

SECONDARY outcome

Timeframe: Baseline, 6 weeks

Population: not assessed (limited funds available)

Oxidative stress was measured by using liquid chromatography to collect plasma glutathione and glutathione disulfide. Change is the difference between 6-week plasma glutathione and glutathione disulfide from baseline plasma glutathione and glutathione disulfide.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 6 weeks

Population: not assessed (limited funds available)

AIx is a surrogate measure of peripheral arterial resistance and is measured by analysis of the pulse wave at the radial artery. The AIx is calculated as the ratio of the pulse pressure at the second systolic peak to that at the first systolic peak. Change is the difference between 6-week AIx from baseline AIx.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 6 weeks

It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week level from baseline level.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Expression of Inflammatory Biomarker Interleukin-6 (IL-6)	-0.29 pg/ml Standard Deviation 0.93	-1.84 pg/ml Standard Deviation 5.43	-0.36 pg/ml Standard Deviation 1.24

SECONDARY outcome

Timeframe: Baseline, 6 weeks

Blood samples were collected for measurement of free fatty acids at baseline and 6 weeks after the Intralipid 20% infusion. FFA levels were determined by colorimetric method. Current guidelines identify normal range of FFA level as less than 0.72 mmol/L. Elevated plasma levels of FFA indicate a greater rate of insulin resistance. Change is the difference between 6-week FFA levels from baseline FFA levels.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in FFA (Free Fatty Acid) Levels From Baseline to 6 Weeks	-0.08 mmol/L Standard Deviation 0.32	0.04 mmol/L Standard Deviation 0.22	0.03 mmol/L Standard Deviation 0.43

SECONDARY outcome

Timeframe: Baseline, 6 weeks

Population: not assessed (limited funds available)

PWV was measured between the carotid and femoral arteries using the SphygmoCor device. Pressure waveforms at the carotid and femoral arteries were acquired using EKG gating. Velocity (distance per time in milliseconds) was calculated using the foot-to-foot method and the distance between the sites was measured manually.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 6 weeks

It is measured by using microsphere-based flow cytometric immunoassay. Change is the difference between 6-week inflammatory biomarker level from baseline level.

Outcome measures

Outcome measures
Measure	Salsalate n=11 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one salsalate 750 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two salsalate 750 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Carvedilol n=8 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one carvedilol 3.125 mg tablet twice daily for two weeks. If the subject had no side effects, the dose was increased to two carvedilol 3.125 mg tablets twice daily for the remaining four weeks. The subjects also received another 24-hour IV administration of Intralipid 20% at the 6-week point.	Placebo n=9 Participants Obese, normotensive, healthy subjects received an intravenous (IV) administration of Intralipid 20% for 24 hours, and then one placebo tablet twice daily for two weeks. The dose was increased to two placebo tablets twice daily for the remaining four weeks. The subjects also receive another 24-hour IV administration of Intralipid 20% at the 6-week point.
Change in Expression of Inflammatory Biomarker C-Reactive Protein (CRP)	2.55 mg/dL Standard Deviation 7.67	-7.08 mg/dL Standard Deviation 17.94	-0.20 mg/dL Standard Deviation 2.82

Adverse Events

Salsalate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Carvedilol

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Guillermo Umpierrez

Emory University

Phone: 404-778-1665

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place