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

Tracking Information
First Submitted Date ICMJE	February 22, 2007
First Posted Date ICMJE	February 26, 2007
Results First Submitted Date	May 28, 2010
Results First Posted Date	August 30, 2010
Last Update Posted Date	September 25, 2014
Study Start Date ICMJE	February 2007
Actual Primary Completion Date	May 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 28, 2010)	Rate of Change on the ADAS-Cog 11. [ Time Frame: Baseline, 6, 12, 18 months ]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 ]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.
Original Primary Outcome Measures ICMJE; (submitted: February 22, 2007)	Changes in rate of cognitive and functional decline measured by ADAS-Cog and CDR-SOB
Change History	Complete list of historical versions of study NCT00440050 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 28, 2010)	ADCS-ADL [ Time Frame: 18 months ]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 ]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.
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	DHA (Docosahexaenoic Acid), an Omega 3 Fatty Acid, in Slowing the Progression of Alzheimer's Disease
Official Title ICMJE	A Randomized Double-Blind Placebo-Controlled Trial Of The Effects Of Docosahexaenoic Acid (DHA) In Slowing The Progression Of Alzheimer's Disease
Brief Summary	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).
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Alzheimer's Disease
Intervention ICMJE	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; Drug: Placebo 2 placebo capsules twice a day for 18 months
Study Arms	Experimental: 1. DHA Intervention: Drug: DHA (Docosahexaenoic Acid); Placebo Comparator: 2. Placebo Intervention: Drug: Placebo
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, Ocké 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.; 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.; Yassine HN, Rawat V, Mack WJ, Quinn JF, Yurko-Mauro K, Bailey-Hall E, Aisen PS, Chui HC, Schneider LS. The effect of APOE genotype on the delivery of DHA to cerebrospinal fluid in Alzheimer's disease. Alzheimers Res Ther. 2016 Jun 30;8:25. doi: 10.1186/s13195-016-0194-x.; 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. doi: 10.1001/jama.2010.1510.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 28, 2010)	402
Original Enrollment ICMJE; (submitted: February 22, 2007)	400
Actual Study Completion Date	May 2009
Actual Primary Completion Date	May 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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)
Sex/Gender	Sexes Eligible for Study: All
Ages	50 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00440050
Other Study ID Numbers ICMJE	IA0099; 1RC2AG036535 ( U.S. NIH Grant/Contract ); ADC-027-DHA
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Alzheimer's Disease Cooperative Study (ADCS)
Study Sponsor ICMJE	Alzheimer's Disease Cooperative Study (ADCS)
Collaborators ICMJE	National Institute on Aging (NIA); DSM Nutritional Products, Inc.
Investigators ICMJE	Principal Investigator: Joseph Quinn, MD Oregon Health and Science University
PRS Account	Alzheimer's Disease Cooperative Study (ADCS)
Verification Date	September 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP