Trial Outcomes & Findings for Functional Research of Emulsifiers in Humans (NCT NCT03440229)

Last Updated: 2021-10-19

Results Overview

Measured distance from the epithelium to the nearest bacteria under high powered microscopy; The measurements were taken on the last day of the diet intervention. An average of 3 measurements was taken.

Recruitment status

COMPLETED

Study phase

Target enrollment

29 participants

Primary outcome timeframe

last day of inpatient stay (either day 17 for the 3 participants with a 17 day inpatient stay or day 11 for the 13 participants with an 11 day inpatient stay.)

Results posted on

2021-10-19

Participant Flow

There were 29 participants who were consented to the study. 8 were found to be ineligible prior to being randomized, 5 additional participants withdrew prior to being randomized saying they were no longer interested or able to participate and 16 participants were randomized.

Participant milestones

Participant milestones
Measure	Emuslfier-free Diet This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Overall Study STARTED	9	7
Overall Study COMPLETED	9	7
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Functional Research of Emulsifiers in Humans

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Emuslfier-free Diet n=9 Participants This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 Participants This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.	Total n=16 Participants Total of all reporting groups
Age, Continuous	41.11 years STANDARD_DEVIATION 12.72 • n=99 Participants	35.24 years STANDARD_DEVIATION 11.28 • n=107 Participants	38.54 years STANDARD_DEVIATION 12.09 • n=206 Participants
Sex: Female, Male Female	6 Participants n=99 Participants	3 Participants n=107 Participants	9 Participants n=206 Participants
Sex: Female, Male Male	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	6 Participants n=99 Participants	3 Participants n=107 Participants	9 Participants n=206 Participants
Race (NIH/OMB) White	3 Participants n=99 Participants	2 Participants n=107 Participants	5 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Height	170.01 cm STANDARD_DEVIATION 12.36 • n=99 Participants	168.22 cm STANDARD_DEVIATION 6.91 • n=107 Participants	169.23 cm STANDARD_DEVIATION 10.07 • n=206 Participants
Weight	69.58 kg STANDARD_DEVIATION 13.16 • n=99 Participants	70.64 kg STANDARD_DEVIATION 10.63 • n=107 Participants	70.05 kg STANDARD_DEVIATION 11.74 • n=206 Participants
BMI	24.06 kg/m2 STANDARD_DEVIATION 3.62 • n=99 Participants	25.02 kg/m2 STANDARD_DEVIATION 3.88 • n=107 Participants	24.48 kg/m2 STANDARD_DEVIATION 3.64 • n=206 Participants
Systolic Blood Pressure	115.33 mmHg STANDARD_DEVIATION 8.53 • n=99 Participants	124.71 mmHg STANDARD_DEVIATION 9.12 • n=107 Participants	119.44 mmHg STANDARD_DEVIATION 9.76 • n=206 Participants
Diastolic Blood Pressure	69.78 mmHg STANDARD_DEVIATION 14.06 • n=99 Participants	71.86 mmHg STANDARD_DEVIATION 8.17 • n=107 Participants	70.69 mmHg STANDARD_DEVIATION 11.55 • n=206 Participants

PRIMARY outcome

Timeframe: last day of inpatient stay (either day 17 for the 3 participants with a 17 day inpatient stay or day 11 for the 13 participants with an 11 day inpatient stay.)

Outcome measures

Outcome measures
Measure	Emuslfier-free Diet n=9 Participants This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 Participants This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Distance of Nearest Bacteria to the Epithelium	17.06776 µm Standard Deviation 5.949757	14.09342 µm Standard Deviation 12.51437

SECONDARY outcome

Timeframe: For 3 participants with a 17 day stay, weight was measured on Day 4 and Day 17 of the inpatient stay. For 13 participants with an 11 day stay, weight was measured on Day 1 and Day 11 of the inpatient stay.

Comparison of weight change during the study period - pre and post intervention. Weight on the last day of the inpatient stay was substracted from weight after the washout period but before the start of the intervention.For 3 participants with a 17 day stay, weight from day 4 of the inpatient stay was substracted from day 17. For 13 with an 11 day stay, weight from Day 1 of the inpatient stay was substracted from Day 11

Outcome measures

Outcome measures
Measure	Emuslfier-free Diet n=9 Participants This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 Participants This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Change in Weight	-1.341 kg Standard Deviation 1.408	-0.8111 kg Standard Deviation 1.228

SECONDARY outcome

Timeframe: For 3 participants with a 17 day stay, area under the glucose curve was measured on days 4 and 17 of the inpatient stay . For 13 participanst with an 11 day stay, area under the glucose curve was measured on days 1 and Day 11 of the inpatient stay.

Area under the glucose concentration curves during the oral glucose tolerance test. These measurements were obtained by subtracting the pre from the post net incremental area under the curve. For 3 participants with a 17 day stay, area under the glucose curve from day 4 of the inpatient stay was substracted from day 17. For 13 participants with an 11 day stay, area under the glucose curve from Day 1 of the inpatient stay was substracted from Day 11

Outcome measures

Outcome measures
Measure	Emuslfier-free Diet n=9 Participants This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 Participants This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Area Under Glucose Concentration Curve	-726.5 μIU*min/mL Standard Deviation 1482.9	-669.6 μIU*min/mL Standard Deviation 1454.8

SECONDARY outcome

Timeframe: For 3 pts. with 17 day stays, area under the curve was measured on days 4 and 17 of the inpatient stay. For 13 pts. with 11 day stays, area under the curve was measured on days 1 and Day 11 of the inpatient stay.

Area under the insulin concentration curves during the oral glucose tolerance test. These measurements were obtained by subtracting the pre from the post net incremental area under the curve. This is measured in microliter international units/milliliter. For 3 participants with a 17 day stay, area under the insulin concentration curve from day 4 of the inpatient stay was substracted from day 17. For 13 participants with an 11 day stay, area under the insulin concentration curve from Day 1 of the inpatient stay was substracted from Day 11

Outcome measures

Outcome measures
Measure	Emuslfier-free Diet n=9 Participants This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 Participants This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Area Under Insulin Concentration Curve	-1325.4 μIU*min/mL Standard Deviation 1444.6	1506.4 μIU*min/mL Standard Deviation 2756.2

SECONDARY outcome

Timeframe: Measured at end of inpatient stay (Day 17 for 3 participants and Day 11 for 13 participants) comparing it to the study start (prior to diet intervention; either day 4 for the 3 participants or day 1 for 13 participants.

Population: One participant on the emulsifier free diet did not answer the last 3 question on the Satiety and Hunger questionnaire.

Desire to eat, hunger, fullness, and prospective food consumption were rated on a 150-mm visual analog scale (VAS) that was adapted from Hill and Blundell in Doucet et al.(see references) The Satiety questionnaire was given before a meal (preprandial) and after the meal (postprandial). The minimum score is 0mm and the maximum score is 150mm for each question. The score prior to the intervention was subtracted from the post intervention score measured on the last day of the inpatient stay. Each question is scored individually. Higher score means more of the characteristic being measured. There are no better or worse outcomes based on these scores.

Outcome measures

Outcome measures
Measure	Emuslfier-free Diet n=9 Participants This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 Participants This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline How hungry do you feel? (pre-prandial at study end minuse pre-prandial at study start)	10.778 millimeters Standard Deviation 62.036	-6.714 millimeters Standard Deviation 23.365
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline How full do you feel? (Post-prandial at study end minus post-prandial at study start)	-17.444 millimeters Standard Deviation 41.564	-12.571 millimeters Standard Deviation 31.989
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline How strong is your desire to eat? (Pre-prandial at Study End Minus pre-prandial at Study Start)	-9.889 millimeters Standard Deviation 45.460	2.857 millimeters Standard Deviation 31.583
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline How much do you think you could eat now? (Preprandial at Study End Minus preprandial at Study Start)	-18.375 millimeters Standard Deviation 46.986	-0.286 millimeters Standard Deviation 47.328
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline Urge to eat? (Pre-prandial at Study End Minus Pre-prandial at Study Start)	7.750 millimeters Standard Deviation 18.235	-9.571 millimeters Standard Deviation 42.442
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline Urge to eat? (Post-prandial at Study End Minus Post-prandial at Study Start)	18.778 millimeters Standard Deviation 41.355	7.429 millimeters Standard Deviation 22.948
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline Preoccupation with thoughts of food (Pre-prandial at Study End Minus Pre-prandial at Study Start)	12.375 millimeters Standard Deviation 33.781	-7.000 millimeters Standard Deviation 43.420
Visual Analog Scale Measurements - Satiety/Hunger - Change From Baseline Preoccupation with thoughts of food (Post-prandial at Study End Minus Post-prandial at Study Start)	31.667 millimeters Standard Deviation 39.138	15.857 millimeters Standard Deviation 24.341

SECONDARY outcome

Timeframe: For the 3 participants with a 17 day inpatiet stay, this was measured on Day 17. For the 13 participants with an 11 day stay, this was measured on Day 11

Fecal lipocalin-2 by Elisa

Outcome measures

Outcome measures
Measure	Emuslfier-free Diet n=9 Participants This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 Participants This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
Fecal Lipocalin-2	588.9959 ng/gm Standard Deviation 180.832	304.3584 ng/gm Standard Deviation 101.7004

Adverse Events

Emuslfier-free Diet

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Emulsifier-containing Diet

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Emuslfier-free Diet n=9 participants at risk This is western style diet prepared without any emulsifiers. Emulsifier free brownies and sorbet are provided daily.	Emulsifier-containing Diet n=7 participants at risk This is a western style diet prepared without any emulsifiers with the exception of the CMC that is included in brownies and sorbet that are provided daily. Emulsifier-containing diet: CMC is one of many synthetic dietary emulsifiers that are incorporated into a variety of processed foods. We have recently shown that, in mice, consumption of P80 and CMC, alters microbiota composition, have pro-inflammatory potential and promote microbiota encroachment into the colonic mucosa, low-grade inflammation, and metabolic syndrome. However, it is not known whether these compounds have similar effects in humans. We would like to study these effects in the human gut microbiota.
General disorders Headache	22.2% 2/9 • Number of events 2 • Participants were asked about adverse events at each visit starting at the screening visit and through the last visit. This is approximately 164 days. At screening, participants were asked about any symptoms they were currently experiencing. Participants were asked at each subsequent visit whether they experienced any AEs since the last visit. They were also asked if previously reported unresolved AEs had resolved. The start/end dates were recorded for each AE along with severity (grade), relatedness to study intervention, and whether any action was taken with the study intervention (i.e. paused intervention, stopped intervention)	14.3% 1/7 • Number of events 1 • Participants were asked about adverse events at each visit starting at the screening visit and through the last visit. This is approximately 164 days. At screening, participants were asked about any symptoms they were currently experiencing. Participants were asked at each subsequent visit whether they experienced any AEs since the last visit. They were also asked if previously reported unresolved AEs had resolved. The start/end dates were recorded for each AE along with severity (grade), relatedness to study intervention, and whether any action was taken with the study intervention (i.e. paused intervention, stopped intervention)
Skin and subcutaneous tissue disorders Rash	11.1% 1/9 • Number of events 1 • Participants were asked about adverse events at each visit starting at the screening visit and through the last visit. This is approximately 164 days. At screening, participants were asked about any symptoms they were currently experiencing. Participants were asked at each subsequent visit whether they experienced any AEs since the last visit. They were also asked if previously reported unresolved AEs had resolved. The start/end dates were recorded for each AE along with severity (grade), relatedness to study intervention, and whether any action was taken with the study intervention (i.e. paused intervention, stopped intervention)	14.3% 1/7 • Number of events 1 • Participants were asked about adverse events at each visit starting at the screening visit and through the last visit. This is approximately 164 days. At screening, participants were asked about any symptoms they were currently experiencing. Participants were asked at each subsequent visit whether they experienced any AEs since the last visit. They were also asked if previously reported unresolved AEs had resolved. The start/end dates were recorded for each AE along with severity (grade), relatedness to study intervention, and whether any action was taken with the study intervention (i.e. paused intervention, stopped intervention)

Additional Information

Dr. James D. Lewis

University of Pennsylvania

Phone: 215-573-5137

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place