NCT01953705

Brief Summary

Brain scans can help identify changes that appear to increase risk for cognitive decline and dementia. Some of these brain changes are thought to reflect actual damage to the small blood vessels that support normal brain function. This clinical trial will determine whether an omega 3 polyunsaturated fatty acid (PUFA) therapy can promote brain health by supporting the small blood vessels in the brain over 3 years in older adults at high risk for cognitive decline and dementia of Alzheimer's type.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
102

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started May 2014

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 24, 2013

Completed
7 days until next milestone

First Posted

Study publicly available on registry

October 1, 2013

Completed
7 months until next milestone

Study Start

First participant enrolled

May 1, 2014

Completed
6.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2021

Completed
Last Updated

September 4, 2020

Status Verified

September 1, 2020

Enrollment Period

6.6 years

First QC Date

September 24, 2013

Last Update Submit

September 2, 2020

Conditions

Age Related Cognitive DeclineAlzheimer's DiseaseVascular DementiaEndothelial DysfunctionExecutive Dysfunction

Keywords

omega 3 fatty acidscognitive declineMRIendothelial functionwhite matterexecutive functionpreventionDTIASL

Outcome Measures

Primary Outcomes (1)

  • total cerebral white matter hyperintensity volume

    quantitative MRI

    annual over 3 years

Secondary Outcomes (4)

  • biomarkers of endothelial health

    annual over 3 years

  • total brain atrophy

    annual over 3 years

  • medial temporal lobe atrophy

    annual over 3 years

  • ventricular expansion

    annual over 3 years

Other Outcomes (4)

  • trail making test part B

    annual over 3 years

  • digit symbol WAIS-R

    annual over 3 years

  • cerebral blood flow

    annual over 3 years

  • +1 more other outcomes

Study Arms (2)

omega 3 polyunsaturated fatty acids

EXPERIMENTAL

1.65 grams of EPA+DHA taken daily over 3 years

Drug: Omega 3 PUFA

Soybean oil

PLACEBO COMPARATOR

1.65 grams of soybean oil taken daily over 3 years

Drug: Placebo

Interventions

Omega 3 PUFADRUG

fish oil concentrate standardized to long chain n-3 PUFA content

Also known as: Fish Oil
omega 3 polyunsaturated fatty acids
PlaceboDRUG
Also known as: Soybean Oil
Soybean oil

Eligibility Criteria

Age75 Years+
Sexall
Healthy VolunteersYes
Age GroupsOlder Adult (65+)

You may qualify if:

  • Non-demented or mild cognitive impairment, defined as Clinical Dementia Rating =0 or 0.5 and MMSE \>=24.
  • Age 75 and older, male and female
  • Total WMH volume ≥ 5 cc
  • Plasma PUFA index (EPA + DHA) \< 110 ug/ml or \< 5.5 weight percent
  • Sufficient English language skills to complete all tests
  • Geriatric Depression Scale - 15 \< 6 documenting absence of a significant depressive syndrome
  • Sufficient vision and hearing to complete all tests
  • Informant available with frequent (at least 1 hour/day or 1 day/week) contact with subject to verify functional status and CDR rating

You may not qualify if:

  • Any dementing illness (AD, vascular dementia, normal pressure hydrocephalus, or Parkinson's disease); dementia defined by CDR ≥ 1, MMSE \< 24
  • Significant disease of the CNS such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis
  • Alcohol or substance abuse according to DSM-IV criteria within the last 2 years
  • Major depression, schizophrenia, or other major psychiatric disorder defined by DSM-IV criteria
  • Abnormal labs indicating vitamin B12 deficiency, thyroid disease, or UTI (documented bacterial colonization is acceptable)
  • Unstable or significantly symptomatic CVD (e.g. CAD with frequent angina, CHF with dyspnea at rest)
  • Hypertension: defined as uncontrolled BP \> 150/90
  • Clinical symptomatic orthostatic hypotension
  • Diabetes mellitus that requires insulin injections
  • History of cortical stroke
  • Cancer within the last 5 years, with the exception of localized prostate cancer (Gleason Grade \< 3) and non-metastatic skin cancers (melanoma).
  • Illness that requires \>1 visit /month to a clinician
  • Contraindications to MRI (i.e., heart pacemaker, metal plates or objects in head, , claustrophobia)
  • Medications:
  • CNS active meds that have not been on stable doses for at least 2 months (cimetidine, beta-blockers, and SSRIs)
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Related Publications (8)

  • Bowman GL, Dayon L, Kirkland R, Wojcik J, Peyratout G, Severin IC, Henry H, Oikonomidi A, Migliavacca E, Bacher M, Popp J. Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults. Alzheimers Dement. 2018 Dec;14(12):1640-1650. doi: 10.1016/j.jalz.2018.06.2857. Epub 2018 Aug 14.

    PMID: 30120040BACKGROUND

  • Alber J, Alladi S, Bae HJ, Barton DA, Beckett LA, Bell JM, Berman SE, Biessels GJ, Black SE, Bos I, Bowman GL, Brai E, Brickman AM, Callahan BL, Corriveau RA, Fossati S, Gottesman RF, Gustafson DR, Hachinski V, Hayden KM, Helman AM, Hughes TM, Isaacs JD, Jefferson AL, Johnson SC, Kapasi A, Kern S, Kwon JC, Kukolja J, Lee A, Lockhart SN, Murray A, Osborn KE, Power MC, Price BR, Rhodius-Meester HFM, Rondeau JA, Rosen AC, Rosene DL, Schneider JA, Scholtzova H, Shaaban CE, Silva NCBS, Snyder HM, Swardfager W, Troen AM, van Veluw SJ, Vemuri P, Wallin A, Wellington C, Wilcock DM, Xie SX, Hainsworth AH. White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities. Alzheimers Dement (N Y). 2019 Apr 9;5:107-117. doi: 10.1016/j.trci.2019.02.001. eCollection 2019.

    PMID: 31011621BACKGROUND

  • Dayon L, Cominetti O, Wojcik J, Galindo AN, Oikonomidi A, Henry H, Migliavacca E, Kussmann M, Bowman GL, Popp J. Proteomes of Paired Human Cerebrospinal Fluid and Plasma: Relation to Blood-Brain Barrier Permeability in Older Adults. J Proteome Res. 2019 Mar 1;18(3):1162-1174. doi: 10.1021/acs.jproteome.8b00809. Epub 2019 Feb 15.

    PMID: 30702894BACKGROUND

  • Bowman GL, Dodge HH, Guyonnet S, Zhou N, Donohue J, Bichsel A, Schmitt J, Hooper C, Bartfai T, Andrieu S, Vellas B; MAPT/DSA Study Group. A blood-based nutritional risk index explains cognitive enhancement and decline in the multidomain Alzheimer prevention trial. Alzheimers Dement (N Y). 2019 Dec 28;5:953-963. doi: 10.1016/j.trci.2019.11.004. eCollection 2019.

    PMID: 31921969BACKGROUND

  • Hooper C, De Souto Barreto P, Coley N, Causse E, Payoux P, Salabert AS, Cesari M, Andrieu S, Bowman GL, Weiner M, Vellas B. Cross-Sectional Associations of Total Plasma Homocysteine with Cortical beta-Amyloid Independently and as a Function of Omega 3 Polyunsaturated Fatty Acid Status in Older Adults at Risk of Dementia. J Nutr Health Aging. 2017;21(10):1075-1080. doi: 10.1007/s12603-017-0989-x.

    PMID: 29188863BACKGROUND

  • Bowman GL, Dodge HH, Mattek N, Barbey AK, Silbert LC, Shinto L, Howieson DB, Kaye JA, Quinn JF. Plasma omega-3 PUFA and white matter mediated executive decline in older adults. Front Aging Neurosci. 2013 Dec 16;5:92. doi: 10.3389/fnagi.2013.00092. eCollection 2013.

    PMID: 24379780BACKGROUND

  • Bowman GL, Silbert LC, Dodge HH, Lahna D, Hagen K, Murchison CF, Howieson D, Kaye J, Quinn JF, Shinto L. Randomized Trial of Marine n-3 Polyunsaturated Fatty Acids for the Prevention of Cerebral Small Vessel Disease and Inflammation in Aging (PUFA Trial): Rationale, Design and Baseline Results. Nutrients. 2019 Mar 29;11(4):735. doi: 10.3390/nu11040735.

    PMID: 30934894RESULT

  • Shinto LH, Murchison CF, Silbert LC, Dodge HH, Lahna D, Rooney W, Kaye J, Quinn JF, Bowman GL. omega-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2024 Aug 1;7(8):e2426872. doi: 10.1001/jamanetworkopen.2024.26872.

    PMID: 39088212DERIVED

MeSH Terms

Conditions

Alzheimer DiseaseDementia, VascularCognitive Dysfunction

Interventions

Fish OilsSoybean Oil

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental DisordersCerebrovascular DisordersIntracranial ArteriosclerosisIntracranial Arterial DiseasesLeukoencephalopathiesArteriosclerosisArterial Occlusive DiseasesVascular DiseasesCardiovascular DiseasesCognition Disorders

Intervention Hierarchy (Ancestors)

OilsLipidsDietary Fats, UnsaturatedDietary FatsFatsFats, UnsaturatedPlant OilsPlant PreparationsBiological ProductsComplex MixturesFoodDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Officials

  • Gene Bowman, ND, MPH

    Oregon Health and Science University

    PRINCIPAL INVESTIGATOR

  • Lynne Shinto, ND, MPH

    Oregon Health and Science University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Affiliate Professor

Study Record Dates

First Submitted

September 24, 2013

First Posted

October 1, 2013

Study Start

May 1, 2014

Primary Completion

December 1, 2020

Study Completion

June 1, 2021

Last Updated

September 4, 2020

Record last verified: 2020-09

Locations

US(1)