A Phase 2/3 interventional study of icosapent ethyl (IPE) and gel cap placebo in Alzheimer's Disease, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 50 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-11-26.
Sponsored by VA Office of Research and Development · Phase 2/3, Interventional, and Prevention
The number of Americans diagnosed with Alzheimer's disease (AD) is expected to triple by 2050. Compared to the general population, Veterans have a greater risk of AD, likely in part due to their increased incidence of traumatic brain injury, post-traumatic stress disorder, depression, and other vascular-related health issues. Based on available data, 423,000 new cases of AD are anticipated in Veterans by 2020. Thus, the discovery of effective therapies to prevent or delay the onset of AD in Veterans is critical. The goal of this study is to evaluate the efficacy of a purified form of the omega-3 fatty acid eicosapentaenoic acid (EPA) called icosapent ethyl (IPE), on improving brain blood flow, spinal fluid markers of AD pathology, and cognitive performance in middle-aged, cognitively-healthy Veterans with increased risk of AD. If IPE delays the onset of AD by even 5 years, the incidence of AD would be reduced by 50% in this population and could have a profound effect on Veteran quality of life and healthcare costs.
The proposed study is a proof-of-concept, randomized, placebo-controlled, double-blind, parallel-group clinical trial assessing the efficacy of 18 months of icosapent ethyl (IPE) therapy on magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and cognitive biomarkers for AD in 150 cognitively-healthy Veterans ages 50-75 years. The overarching goal of this trial is to assess whether icosapent ethyl beneficially affects intermediate physiological measures associated with onset of AD in order to evaluate whether larger, multi-site, longer-duration Alzheimer's prevention trials are warranted to assess more definitive clinical outcomes. The proposed study aims to: 1) investigate the effects of 18 months of IPE vs. placebo on regional cerebral blood flow as measured by arterial spin-labeling MRI; 2) determine the impact of 18 months of IPE vs. placebo on CSF biomarkers of AD pathology; and 3) evaluate the effects of 18 months of IPE vs. placebo on cognitive performance.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 131 is above the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
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Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.
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Exclusion Criteria:
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Drug: icosapent ethyl (IPE)
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Other: gel cap placebo
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Also known as: Vascepa
Participants will be randomized in a 1:1 ratio to receive icosapent ethyl 4 g daily vs. matching gel cap placebo
Also known as: Placebo
Regional Cerebral Blood Flow Using Arterial Spin-labeling MRI
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.
Time frame: 18 month study visit
Cerebrospinal Fluid (CSF) Biomarkers of Alzheimer's Disease
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.
Time frame: 18 month study visit
Cognitive Performance
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.
Time frame: 18 month study visit
| Milestone | Icosapent Ethyl (IPE) | Placebo |
|---|---|---|
| Started | 63 | 68 |
| Completed | 52 | 60 |
| Not completed | 11 | 8 |
| Withdrew: Withdrawal by subject | 11 | 8 |
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.
| mL/g/min | Icosapent Ethyl (IPE) | Placebo |
|---|---|---|
| Regional Cerebral Blood Flow Using Arterial Spin-labeling MRI | 55.7 ± 14.6 | 54.5 ± 14.1 |
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.
| pg/mL | Icosapent Ethyl (IPE) | Placebo |
|---|---|---|
| beta-amyloid(1-42) | 1281.7 ± 558.5 | 1244.6 ± 607.7 |
| phosphorylated tau(181) | 20.2 ± 8.13 | 18.8 ± 5.56 |
| Total tau | 218.2 ± 83.6 | 208.0 ± 63.7 |
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.
| Z-score | Icosapent Ethyl (IPE) | Placebo |
|---|---|---|
| Cognitive Performance | 0.455 ± 1.22 | 0.611 ± 1.10 |
Collected over 18 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Icosapent Ethyl (IPE) | 0/63 (0%) | 9/63 (14.3%) | 13/63 (20.6%) |
| Placebo | 1/68 (1.5%) | 7/68 (10.3%) | 19/68 (27.9%) |
| Event | Icosapent Ethyl (IPE) | Placebo |
|---|---|---|
| FallInjury, poisoning and procedural complications | 2/63 | 0/68 |
| Chest pain or tightnessCardiac disorders | 1/63 | 0/68 |
| Laparoscopic prostatectomySurgical and medical procedures | 1/63 | 0/68 |
| SurgeryCardiac disorders | 1/63 | 0/68 |
| Aortic aneurysmCardiac disorders | 1/63 | 0/68 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 1/63 | 0/68 |
| DehydrationGeneral disorders | 1/63 | 1/68 |
| Urinary tract infectionRenal and urinary disorders | 1/63 | 0/68 |
| MortatiltyGeneral disorders | 0/63 | 1/68 |
| COPDRespiratory, thoracic and mediastinal disorders | 0/63 | 1/68 |
| Event | Icosapent Ethyl (IPE) | Placebo |
|---|---|---|
| Muscle painMusculoskeletal and connective tissue disorders | 3/63 | 5/68 |
| HeadacheInjury, poisoning and procedural complications | 1/63 | 2/68 |
| AccidentInjury, poisoning and procedural complications | 1/63 | 2/68 |
| AbscessSkin and subcutaneous tissue disorders | 0/63 | 2/68 |
| Atrial fibrillationCardiac disorders | 0/63 | 2/68 |
| BloatingGastrointestinal disorders | 0/63 | 2/68 |
| CancerReproductive system and breast disorders | 1/63 | 2/68 |
| ItchingSkin and subcutaneous tissue disorders | 1/63 | 0/68 |
| Distended bladderRenal and urinary disorders | 1/63 | 0/68 |
| ConstipationGastrointestinal disorders | 1/63 | 0/68 |
| Age, Continuous(years) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| Mean | 65.9 ± 7.06 | 65.4 ± 7.00 | 65.5 ± 7.00 |
| Sex/Gender, Customized(Participants) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| Female | 9 | 8 | 17 |
| Male | 52 | 60 | 112 |
| Unknown | 2 | 0 | 2 |
| Race (NIH/OMB)(Participants) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 2 |
| White | 61 | 65 | 126 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 1 | 2 |
| Education(Participants) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| GED or ABE certificate | 1 | 2 | 3 |
| High school diploma | 8 | 10 | 18 |
| Trade or technical school graduate | 8 | 3 | 11 |
| Some college but not a 2- or 4-year degree | 12 | 15 | 27 |
| 2-year college degree (AA or equivalent) | 14 | 8 | 22 |
| 4-year college degree (Bachelor's) | 11 | 17 | 28 |
| Master's degree | 8 | 12 | 20 |
| Did not graduate from high school | 0 | 1 | 1 |
| Unknown | 1 | 0 | 1 |
| APOE risk allele(Participants) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| Carrier | 11 | 19 | 30 |
| Non-Carrier | 52 | 49 | 101 |
| Parental history of Alzheimer's disease(Participants) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| Yes | 29 | 32 | 61 |
| No | 33 | 36 | 69 |
| Unknown | 1 | 0 | 1 |
| Systolic blood pressure(mm/Hg) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| Mean | 136.2 ± 16.4 | 136.1 ± 16.5 | 136.1 ± 16.4 |
| Total Cholesterol(mg/dL) | Icosapent Ethyl (IPE) | Placebo | Total |
|---|---|---|---|
| Mean | 173.2 ± 41.4 | 168.3 ± 45.2 | 170.6 ± 43.3 |
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