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n-3 PUFA for Vascular Cognitive Aging

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ClinicalTrials.gov Identifier: NCT01953705
Recruitment Status : Active, not recruiting
First Posted : October 1, 2013
Last Update Posted : June 17, 2019
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Lynne Shinto, Oregon Health and Science University

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.

Condition or disease Intervention/treatment Phase
Age Related Cognitive Decline Alzheimer's Disease Vascular Dementia Endothelial Dysfunction Executive Dysfunction Drug: Omega 3 PUFA Drug: Placebo Phase 2

Detailed Description:

The main objective of this study is to determine if omega 3 PUFA can slow the accumulation of brain MRI derived white matter hyper-intensities (WMH) over 3 years in a population at risk for dementia. This trial is designed to collect preliminary data into the mechanism by which PUFA therapy operates on the brain with special attention to the vascular components.

The randomized, double-blind and controlled trial will rigorously test PUFA effects versus a placebo in non-demented elders over 3 years. This biomarker based trial will enroll 100 elders. Aim 1 will assess PUFA effects on neuroimaging parameter changes. Aim 2 will assess PUFA effects on blood-based biomarkers of endothelial health, and Aim 3 will collect preliminary data on PUFA effects on neuropsychological and functional parameters with special attention to the executive and speed of processing skills and gait speed.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Omega 3 PUFA for the Vascular Component of Age-related Cognitive Decline
Study Start Date : May 2014
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Experimental: omega 3 polyunsaturated fatty acids
1.65 grams of EPA+DHA taken daily over 3 years
Drug: Omega 3 PUFA
fish oil concentrate standardized to long chain n-3 PUFA content
Other Name: Fish Oil

Placebo Comparator: Soybean oil
1.65 grams of soybean oil taken daily over 3 years
Drug: Placebo
Other Name: Soybean Oil




Primary Outcome Measures :
  1. total cerebral white matter hyperintensity volume [ Time Frame: annual over 3 years ]
    quantitative MRI


Secondary Outcome Measures :
  1. biomarkers of endothelial health [ Time Frame: annual over 3 years ]
    blood based

  2. total brain atrophy [ Time Frame: annual over 3 years ]
    quantitative MRI

  3. medial temporal lobe atrophy [ Time Frame: annual over 3 years ]
    quantitative MRI

  4. ventricular expansion [ Time Frame: annual over 3 years ]
    quantitative MRI


Other Outcome Measures:
  1. trail making test part B [ Time Frame: annual over 3 years ]
    neuropsych

  2. digit symbol WAIS-R [ Time Frame: annual over 3 years ]
    neuropsyh

  3. cerebral blood flow [ Time Frame: annual over 3 years ]
    arterial spin labeling

  4. fractional anisotropy within frontal gyri [ Time Frame: annual over 3 years ]
    diffusion tensor imaging



Information from the National Library of Medicine

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Ages Eligible for Study:   75 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Non-demented or mild cognitive impairment, defined as Clinical Dementia Rating =0 or 0.5 and MMSE >=24.
  2. Age 75 and older, male and female
  3. Total WMH volume ≥ 5 cc
  4. Plasma PUFA index (EPA + DHA) < 110 ug/ml or < 5.5 weight percent
  5. Sufficient English language skills to complete all tests
  6. Geriatric Depression Scale - 15 < 6 documenting absence of a significant depressive syndrome
  7. Sufficient vision and hearing to complete all tests
  8. Informant available with frequent (at least 1 hour/day or 1 day/week) contact with subject to verify functional status and CDR rating
  9. General health status that will not interfere with the ability to complete the prospective study (these conditions are listed below in the study exclusion list)

Exclusion Criteria:

  1. Any dementing illness (AD, vascular dementia, normal pressure hydrocephalus, or Parkinson's disease); dementia defined by CDR ≥ 1, MMSE < 24
  2. Significant disease of the CNS such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis
  3. Alcohol or substance abuse according to DSM-IV criteria within the last 2 years
  4. Major depression, schizophrenia, or other major psychiatric disorder defined by DSM-IV criteria
  5. Abnormal labs indicating vitamin B12 deficiency, thyroid disease, or UTI (documented bacterial colonization is acceptable)
  6. Unstable or significantly symptomatic CVD (e.g. CAD with frequent angina, CHF with dyspnea at rest)
  7. Hypertension: defined as uncontrolled BP > 150/90
  8. Clinical symptomatic orthostatic hypotension
  9. Diabetes mellitus that requires insulin injections
  10. History of cortical stroke
  11. Cancer within the last 5 years, with the exception of localized prostate cancer (Gleason Grade < 3) and non-metastatic skin cancers (melanoma).
  12. Illness that requires >1 visit /month to a clinician
  13. Contraindications to MRI (i.e., heart pacemaker, metal plates or objects in head, , claustrophobia)
  14. Medications:

    1. CNS active meds that have not been on stable doses for at least 2 months (cimetidine, beta-blockers, and SSRIs)
    2. Neuroleptics, antiparkinsonian agents, systemic corticosteroids, and narcotic analgesics; in the case where these were used for a self-limited time they must have been discounted for a period of five half-lives prior to baseline visit
    3. Over the counter supplements are not by themselves exclusionary, however, subjects are asked not to change the dosing regimen over the course of the trial unless medically indicated; the presence and dose of these agents are recorded
    4. A baseline screen plasma PUFA > 5.5 weight percent of total fatty acids for EPA+DHA will confirm supplementation of O3PUFA history. If patient indicates regular supplementation with fish oil on phone screen, can wash out for 4 months prior to study visit one.
    5. Cholinesterase inhibitors (i.e., Aricept)
    6. Investigational drugs within five half-lives prior to baseline
    7. Anticoagulation therapy: Vitamin K antagonist: warfarin (Coumadin, jantoven), Factor Xa inhibitors: rivaroxaban (xarelto), fondaparinux (arixtra), dibigatran (pradaxa), apixaban (eliquis); Low molecular weight heparins: dalteparin (fragmin), enoxaparin (lovenox)(Incident use of anticoagulant therapy will exclude further study drug allocation. However, subjects will be asked to complete all follow-up visits.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01953705


Locations
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United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Gene Bowman, ND, MPH Oregon Health and Science University
Principal Investigator: Lynne Shinto, ND, MPH Oregon Health and Science University

Publications of Results:
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Responsible Party: Lynne Shinto, Associate Professor, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT01953705     History of Changes
Other Study ID Numbers: R01AG043398 ( U.S. NIH Grant/Contract )
R01AG043398-01A1 ( U.S. NIH Grant/Contract )
First Posted: October 1, 2013    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019
Keywords provided by Lynne Shinto, Oregon Health and Science University:
omega 3 fatty acids
cognitive decline
MRI
endothelial function
white matter
executive function
prevention
DTI
ASL
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia, Vascular
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases