DHA (Docosahexaenoic Acid), an Omega 3 Fatty Acid, in Slowing the Progression of Alzheimer's Disease

Alzheimer's Disease Cooperative Study (ADCS)

Status and phase

Completed

Phase 3

Conditions

Alzheimer's Disease

Treatments

Drug: Placebo

Drug: DHA (Docosahexaenoic Acid)

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT00440050

IA0099

1RC2AG036535 (U.S. NIH Grant/Contract)

ADC-027-DHA

Details and patient eligibility

About

The purpose of this study is to determine whether chronic DHA (Docosahexaenoic Acid) supplementation slows the progression of cognitive and functional decline in mild to moderate Alzheimer's disease (AD).

Full description

Preliminary studies have shown a reduced risk of Alzheimer's disease (AD) in people consuming increased amounts of fish in their diets. Many of the health benefits of fish are attributed to the abundance of omega 3 fatty acids. Docosahexaenoic Acid (DHA) is the most abundant omega 3 fatty acid in the brain. Data from several animal models supports the hypothesis that DHA may be an effective treatment for AD by means of anti-amyloid, antioxidant, and neuroprotectant mechanisms.

In this study, 400 individuals with mild to moderate AD will participate at approximately 53 study sites throughout the US for 18 months. Participants will be randomized so that 60% will receive approximately 2 grams of DHA, divided into 4 capsules, 2 capsules taken twice a day, while 40% receive an identical placebo.

Potential participants will go to their study site for a screening visit, where eligibility is determined, and if accepted, for a baseline visit where cognitive status, behavioral status, functional status, and global severity of dementia will be assessed. Vital signs and biomarker labs will also be obtained. Subsequent visits will occur every three months for medication checks and, every 6 months, further assessments, physical exams, and labs.

Some participants will also take part in MRI (magnetic resonance imaging) and/or CSF (cerebrospinal fluid) sub-studies. For the MRI sub-study, scans will be done prior to beginning the study medication, and again after 18 months. Likewise, for the CSF sub-study, a lumbar puncture will be done prior to beginning the study medication, and again after 18 months.

Enrollment is restricted to individuals who consume no more than 200 mg of DHA per day, which is almost 300% of the average daily intake in an American diet. Individuals who take fish oil or omega 3 fatty acid supplements are also not eligible. Each visit will include completion of a very brief food frequency questionnaire to monitor dietary DHA levels.

Enrollment

402 patients

Sex

All

Ages

50+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female
50 years of age or older
Residing in the community at baseline (includes assisted living facilities, but excludes long-term care nursing facilities)
MMSE (Mini-Mental State Examination) at screen of 14-26 (inclusive)
No medical contraindications to study participation
Fluent in English or Spanish
Corrected vision and hearing sufficient for compliance with testing procedures
Supervision available for study medication
Caregiver/study partner to accompany participant to all visits
Study partner must have direct contact with the participant more than 2 days/week
Able to ingest oral medication
Daily DHA consumption less than or equal to 200 mg/day in prior two months estimated by an abbreviated DHA food frequency questionnaire
Neuroimaging consistent with the diagnosis of AD at some time after the onset of the memory decline
Clinical laboratory values must be within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator
Stable use of cholinesterase inhibitors and memantine is permitted if doses are stable for 4 months prior to enrollment

Exclusion criteria

Non-AD dementia
Residence in a long-term care facility at baseline
History of clinically significant stroke
Modified Hachinski Ischemia score ≥ 4
Current evidence or history in past two years of epilepsy, seizure, focal brain lesion, head injury with loss of consciousness or DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
Sensory impairment which would prevent subject from participating in or cooperating with the protocol
Use of another investigational agent within two months
Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational new drug including clinically significant or unstable hematologic, hepatic, cardiovascular (including history of ventricular fibrillation or ventricular tachycardia), pulmonary, gastrointestinal, endocrine, metabolic, renal, or other systemic disease or laboratory abnormality
Active neoplastic disease (skin tumors other than melanoma may be included; participants with stable prostate cancer may be included at the discretion of the Project Director)