Trial Outcomes & Findings for Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid (NCT NCT02719327)

NCT ID: NCT02719327

Last Updated: 2024-11-26

Results Overview

For the primary outcome we chose an anatomical region, posterior cingulate gyrus, that aligned with statistical region of interest sensitive to changes in cerebral blood flow in cognitively-unimpaired adults at risk for Alzheimer's disease. Brain blood flow was averaged across the right and left posterior cingulate gyrus.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

131 participants

Primary outcome timeframe

18 month study visit

Results posted on

2024-11-26

Participant Flow

Participant milestones

Participant milestones
Measure	Icosapent Ethyl (IPE) Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Overall Study STARTED	63	68
Overall Study COMPLETED	52	60
Overall Study NOT COMPLETED	11	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Icosapent Ethyl (IPE) Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Overall Study Withdrawal by Subject	11	8

Baseline Characteristics

Brain Amyloid and Vascular Effects of Eicosapentaenoic Acid

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Icosapent Ethyl (IPE) n=63 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo n=68 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Total n=131 Participants Total of all reporting groups
Age, Continuous	65.9 years STANDARD_DEVIATION 7.06 • n=99 Participants	65.4 years STANDARD_DEVIATION 7.00 • n=107 Participants	65.5 years STANDARD_DEVIATION 7.00 • n=206 Participants
Sex/Gender, Customized Female	9 Participants n=99 Participants	8 Participants n=107 Participants	17 Participants n=206 Participants
Sex/Gender, Customized Male	52 Participants n=99 Participants	60 Participants n=107 Participants	112 Participants n=206 Participants
Sex/Gender, Customized Unknown	2 Participants n=99 Participants	0 Participants n=107 Participants	2 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	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	61 Participants n=99 Participants	65 Participants n=107 Participants	126 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Education GED or ABE certificate	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Education High school diploma	8 Participants n=99 Participants	10 Participants n=107 Participants	18 Participants n=206 Participants
Education Trade or technical school graduate	8 Participants n=99 Participants	3 Participants n=107 Participants	11 Participants n=206 Participants
Education Some college but not a 2- or 4-year degree	12 Participants n=99 Participants	15 Participants n=107 Participants	27 Participants n=206 Participants
Education 2-year college degree (AA or equivalent)	14 Participants n=99 Participants	8 Participants n=107 Participants	22 Participants n=206 Participants
Education 4-year college degree (Bachelor's)	11 Participants n=99 Participants	17 Participants n=107 Participants	28 Participants n=206 Participants
Education Master's degree	8 Participants n=99 Participants	12 Participants n=107 Participants	20 Participants n=206 Participants
Education Did not graduate from high school	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Education Unknown	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
APOE risk allele Carrier	11 Participants n=99 Participants	19 Participants n=107 Participants	30 Participants n=206 Participants
APOE risk allele Non-Carrier	52 Participants n=99 Participants	49 Participants n=107 Participants	101 Participants n=206 Participants
Parental history of Alzheimer's disease Yes	29 Participants n=99 Participants	32 Participants n=107 Participants	61 Participants n=206 Participants
Parental history of Alzheimer's disease No	33 Participants n=99 Participants	36 Participants n=107 Participants	69 Participants n=206 Participants
Parental history of Alzheimer's disease Unknown	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Systolic blood pressure	136.2 mm/Hg STANDARD_DEVIATION 16.4 • n=99 Participants	136.1 mm/Hg STANDARD_DEVIATION 16.5 • n=107 Participants	136.1 mm/Hg STANDARD_DEVIATION 16.4 • n=206 Participants
Total Cholesterol	173.2 mg/dL STANDARD_DEVIATION 41.4 • n=99 Participants	168.3 mg/dL STANDARD_DEVIATION 45.2 • n=107 Participants	170.6 mg/dL STANDARD_DEVIATION 43.3 • n=206 Participants

PRIMARY outcome

Timeframe: 18 month study visit

Population: Analysis sample is intent-to-treat (ITT), ASL values were imputed from baseline values for 23 participants (n=14 IPE and n=9 placebo); 17 participants lacked baseline ASL values (n=9 IPE, n=8 placebo) and could not be included in analyses.

Outcome measures

Outcome measures
Measure	Icosapent Ethyl (IPE) n=54 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo n=60 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Regional Cerebral Blood Flow Using Arterial Spin-labeling MRI	55.7 mL/g/min Standard Deviation 14.6	54.5 mL/g/min Standard Deviation 14.1

SECONDARY outcome

Timeframe: 18 month study visit

Population: Analysis is based on an intent-to-treat, n=19 participants dropped out prior to receiving an 18 month lumbar puncture (n=11 IPE, n=8 placebo); 26 participants opted out of the lumbar puncture procedure (n=11 IPE, n=15 placebo)

CSF beta-amyloid-42, total tau, and phosphorylated tau-181 (Roche Cobas Elecsys e611). Lower CSF beta-amyloid-42 and higher phosphorylated tau-181 or total tau are associated with risk for Alzheimer's disease.

Outcome measures

Outcome measures
Measure	Icosapent Ethyl (IPE) n=41 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo n=45 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Cerebrospinal Fluid (CSF) Biomarkers of Alzheimer's Disease beta-amyloid(1-42)	1281.7 pg/mL Standard Deviation 558.5	1244.6 pg/mL Standard Deviation 607.7
Cerebrospinal Fluid (CSF) Biomarkers of Alzheimer's Disease phosphorylated tau(181)	20.2 pg/mL Standard Deviation 8.13	18.8 pg/mL Standard Deviation 5.56
Cerebrospinal Fluid (CSF) Biomarkers of Alzheimer's Disease Total tau	218.2 pg/mL Standard Deviation 83.6	208.0 pg/mL Standard Deviation 63.7

SECONDARY outcome

Timeframe: 18 month study visit

Population: Analyses were conducted on an intent-to-treat basis. 19 participants dropped out prior to month 18 study visit (n=11 IPE, n=8)

Alzheimer's Disease Cooperative Study Preclinical Alzheimer's Cognitive Composite (ADCS-PACC). Composite scores at each time point are standardize to baseline values such that at baseline the mean=0 and the standard deviation = 1. Standardized scores range from -3.15 to 3.09. Higher scores indicate better cognition.

Outcome measures

Outcome measures
Measure	Icosapent Ethyl (IPE) n=52 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo n=60 Participants Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Cognitive Performance	0.455 Z-score Standard Deviation 1.22	0.611 Z-score Standard Deviation 1.10

Adverse Events

Icosapent Ethyl (IPE)

Serious events: 9 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 19 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Icosapent Ethyl (IPE) n=63 participants at risk Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo n=68 participants at risk Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
General disorders Mortatilty	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Respiratory, thoracic and mediastinal disorders COPD	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Cardiac disorders Chest pain or tightness	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Surgical and medical procedures Laparoscopic prostatectomy	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Cardiac disorders Surgery	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Cardiac disorders Sinus bradycardia	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Cardiac disorders Aortic aneurysm	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Cardiac disorders non-ST elevated myocardial infarction	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
General disorders Throat infection	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
General disorders Dehydration	1.6% 1/63 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Injury, poisoning and procedural complications Fall	3.2% 2/63 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Renal and urinary disorders Urinary tract infection	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Vascular disorders Hypertension	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.

Other adverse events

Additional Information

Cynthia Carlsson, MD, MS; Professor of Medicine (Geriatrics)

Madison Veterans Affairs Geriatrics Research, Education & Clinical Center (GRECC)

Phone: 608-280-7000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Icosapent Ethyl (IPE) n=63 participants at risk Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo icosapent ethyl (IPE): Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo	Placebo n=68 participants at risk Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo gel cap placebo: Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Surgical and medical procedures orthopedic	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Injury, poisoning and procedural complications Headache	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	2.9% 2/68 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Injury, poisoning and procedural complications Accident	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	2.9% 2/68 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Musculoskeletal and connective tissue disorders Muscle pain	4.8% 3/63 • Number of events 3 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	7.4% 5/68 • Number of events 5 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Synovial cyst	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Skin and subcutaneous tissue disorders Itching	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Skin and subcutaneous tissue disorders Abscess	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	2.9% 2/68 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Renal and urinary disorders Distended bladder	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Renal and urinary disorders Hematoma	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Cardiac disorders Atrial fibrillation	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	2.9% 2/68 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Injury, poisoning and procedural complications Fall	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Gastrointestinal disorders Diarrhea	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Gastrointestinal disorders Bloating	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	2.9% 2/68 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Gastrointestinal disorders Constipation	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Infections and infestations Cellulitus, eye	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Infections and infestations COVID19	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Gastrointestinal disorders Hemorrhoids	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Reproductive system and breast disorders Cancer	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	2.9% 2/68 • Number of events 2 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Gastrointestinal disorders Cancer	0.00% 0/63 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	1.5% 1/68 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.
Infections and infestations Sinus infection	1.6% 1/63 • Number of events 1 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.	0.00% 0/68 • 18 months Participants were assessed for adverse events at months 1, 3, 6, 9, 12, 15, and 18.