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

Sponsor:	Alzheimer's Disease Cooperative Study (ADCS)
Collaborators:	National Institute on Aging (NIA) Martek Biosciences Corporation
Information provided by (Responsible Party):	Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier:	NCT00440050

Purpose

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).

Condition	Intervention	Phase
Alzheimer's Disease	Drug: DHA (Docosahexaenoic Acid) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized Double-Blind Placebo-Controlled Trial Of The Effects Of Docosahexaenoic Acid (DHA) In Slowing The Progression Of Alzheimer's Disease

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease

Drug Information available for: Docosahexaenoic acids Eicosapentaenoic acid Sodium dehydroacetate

U.S. FDA Resources

Further study details as provided by Alzheimer's Disease Cooperative Study (ADCS):

Primary Outcome Measures:

Rate of Change on the ADAS-Cog 11. [ Time Frame: Baseline, 6, 12, 18 months ] [ Designated as safety issue: No ]
ADAS-cog 11 = Alzheimer's Disease Assessment Scale, cognitive sub-scale in points per year. This is a psychometric measure sensitive to change in mild to moderate AD. The range of this instrument is 0 to 70 with higher numbers indicating greater impairment.
Rate of Change on CDR-SOB [ Time Frame: 18 months ] [ Designated as safety issue: No ]
CDR-SOB = Clinical Dementia Rating, Sum of Boxes. This is a global rating of dementia severity based on the clinician's interpretation of the history and examination. The range of this instrument is 0 to 18 with higher numbers indicating greater impairment.

Secondary Outcome Measures:

ADCS-ADL [ Time Frame: 18 months ] [ Designated as safety issue: No ]
ADCS-ADL = Alzheimer's Disease Cooperative Study Activities of Daily Living Score. This is a structured questionnaire about activities of daily living, administered to the subject's caregiver/study partner. The range of this instrument is 0 to 6 with lower numbers indicating greater impairment.
Neuropsychiatric Inventory (NPI) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
The Neuropsychiatric Inventory quantifies behavioral changes in dementia, including depression, anxiety, psychosis, agitation, sleep change, appetite change, and others. This is a structured questionnaire administered to the subject's caregiver/study partner. The range of this instrument is 0 to 120 with higher numbers indicating greater impairment.

Enrollment:	402
Study Start Date:	February 2007
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1. DHA	Drug: DHA (Docosahexaenoic Acid) 950 mg soft-gel capsules which contain approximately 510 mg DHA, 2 capsules twice a day for 18 months Other Name: Neuromins
Placebo Comparator: 2. Placebo	Drug: Placebo 2 placebo capsules twice a day for 18 months

Detailed 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.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00440050

Show 51 Study Locations

Sponsors and Collaborators

Alzheimer's Disease Cooperative Study (ADCS)

National Institute on Aging (NIA)

Martek Biosciences Corporation

Investigators

Principal Investigator:

Joseph Quinn, MD

Oregon Health and Science University

More Information

Publications:

Horrocks LA, Farooqui AA. Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot Essent Fatty Acids. 2004 Apr;70(4):361-72. Review.

Kalmijn S, van Boxtel MP, Ocke M, Verschuren WM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology. 2004 Jan 27;62(2):275-80.

Morris MC, Evans DA, Bienias JL, Tangney CC, Bennett DA, Wilson RS, Aggarwal N, Schneider J. Consumption of fish and n-3 fatty acids and risk of incident Alzheimer disease. Arch Neurol. 2003 Jul;60(7):940-6.

Suzuki H, Morikawa Y, Takahashi H. Effect of DHA oil supplementation on intelligence and visual acuity in the elderly. World Rev Nutr Diet. 2001;88:68-71. No abstract available.

Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, Rostaing P, Triller A, Salem N Jr, Ashe KH, Frautschy SA, Cole GM. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron. 2004 Sep 2;43(5):633-45.

Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005 Mar 23;25(12):3032-40.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Quinn JF, Raman R, Thomas RG, Yurko-Mauro K, Nelson EB, Van Dyck C, Galvin JE, Emond J, Jack CR Jr, Weiner M, Shinto L, Aisen PS. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA. 2010 Nov 3;304(17):1903-11.

Responsible Party:	Alzheimer's Disease Cooperative Study (ADCS)
ClinicalTrials.gov Identifier:	NCT00440050 History of Changes
Other Study ID Numbers:	IA0099, 1RC2AG036535, ADC-027-DHA
Study First Received:	February 22, 2007
Results First Received:	May 28, 2010
Last Updated:	January 18, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Alzheimer's Disease Cooperative Study (ADCS):

fish oil
omega-3 fatty acids
EPA

Additional relevant MeSH terms:

Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on February 09, 2012