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

This study has been completed.

Sponsor:

Collaborators:

National Institute on Aging (NIA)

Martek Biosciences Corporation

Information provided by (Responsible Party):

Alzheimer's Disease Cooperative Study (ADCS)

ClinicalTrials.gov Identifier:

NCT00440050

First received: February 22, 2007

Last updated: May 15, 2013

Last verified: May 2013

History of Changes

Results First Received: May 28, 2010

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
Condition:	Alzheimer's Disease
Interventions:	Drug: DHA (Docosahexaenoic Acid) Drug: Placebo

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were recruited at 51 sites in the United States between February and November 2007.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of 555 subjects screened, 402 met the study criteria and were randomized.

Reporting Groups

	Description
Placebo	Dosing of 2 grams of placebo administered in a divided dose twice daily with food.
Docosahexaenoic Acid (DHA)	Dosing of 2 grams of DHA administered in a divided dose twice daily with food.

Participant Flow: Overall Study

	Placebo	Docosahexaenoic Acid (DHA)
STARTED	164	238
COMPLETED	124	171
NOT COMPLETED	40	67

Baseline Characteristics

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Reporting Groups

	Description
Placebo	Dosing of 2 grams of placebo administered in a divided dose twice daily with food.
Docosahexaenoic Acid (DHA)	Dosing of 2 grams of DHA administered in a divided dose twice daily with food.
Total	Total of all reporting groups

Baseline Measures

	Placebo	Docosahexaenoic Acid (DHA)	Total
Number of Participants [units: participants]	164	238	402
Age [units: years] Mean ± Standard Deviation	76 ± 9.3	76 ± 7.8	76 ± 8.7
Gender [units: participants]
Female	98	112	210
Male	66	126	192
Region of Enrollment [units: participants]
United States	164	238	402

Outcome Measures

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1. Primary:

Rate of Change on the ADAS-Cog 11. [ Time Frame: Baseline, 6, 12, 18 months ]

Measure Type	Primary
Measure Title	Rate of Change on the ADAS-Cog 11.
Measure Description	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.
Time Frame	Baseline, 6, 12, 18 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Placebo	Dosing of 2 grams of placebo administered in a divided dose twice daily with food.
Docosahexaenoic Acid (DHA)	Dosing of 2 grams of DHA administered in a divided dose twice daily with food.

Measured Values

	Placebo	Docosahexaenoic Acid (DHA)
Number of Participants Analyzed [units: participants]	164	238
Rate of Change on the ADAS-Cog 11. [units: ADAS points per year] Mean ± Standard Deviation	7.98 ± 9.84	8.27 ± 8.9

No statistical analysis provided for Rate of Change on the ADAS-Cog 11.

2. Primary:

Rate of Change on CDR-SOB [ Time Frame: 18 months ]

Measure Type	Primary
Measure Title	Rate of Change on CDR-SOB
Measure Description	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.
Time Frame	18 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Placebo	Dosing of 2 grams of placebo administered in a divided dose twice daily with food.
Docosahexaenoic Acid (DHA)	Dosing of 2 grams of DHA administered in a divided dose twice daily with food.

Measured Values

	Placebo	Docosahexaenoic Acid (DHA)
Number of Participants Analyzed [units: participants]	164	238
Rate of Change on CDR-SOB [units: Units on a scale] Mean ± Standard Deviation	2.87 ± 2.93	2.93 ± 2.83

No statistical analysis provided for Rate of Change on CDR-SOB

3. Secondary:

ADCS-ADL [ Time Frame: 18 months ]

Measure Type	Secondary
Measure Title	ADCS-ADL
Measure Description	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.
Time Frame	18 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Placebo	Dosing of 2 grams of placebo administered in a divided dose twice daily with food.
Docosahexaenoic Acid (DHA)	Dosing of 2 grams of DHA administered in a divided dose twice daily with food.

Measured Values

	Placebo	Docosahexaenoic Acid (DHA)
Number of Participants Analyzed [units: participants]	164	238
ADCS-ADL [units: Units on a scale] Mean ± Standard Deviation	10.43 ± 11.74	11.51 ± 13.23

No statistical analysis provided for ADCS-ADL

4. Secondary:

Neuropsychiatric Inventory (NPI) [ Time Frame: 18 months ]

Measure Type	Secondary
Measure Title	Neuropsychiatric Inventory (NPI)
Measure Description	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.
Time Frame	18 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Placebo	Dosing of 2 grams of placebo administered in a divided dose twice daily with food.
Docosahexaenoic Acid (DHA)	Dosing of 2 grams of DHA administered in a divided dose twice daily with food.

Measured Values

	Placebo	Docosahexaenoic Acid (DHA)
Number of Participants Analyzed [units: participants]	164	238
Neuropsychiatric Inventory (NPI) [units: Units on a scale] Mean ± Standard Deviation	2.93 ± 13.62	5.09 ± 15.08

No statistical analysis provided for Neuropsychiatric Inventory (NPI)

Serious Adverse Events

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Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Placebo	Dosing of 2 grams of placebo administered in a divided dose twice daily with food.
Docosahexaenoic Acid (DHA)	Dosing of 2 grams of DHA administered in a divided dose twice daily with food.

Serious Adverse Events

	Placebo	Docosahexaenoic Acid (DHA)
Total, serious adverse events
# participants affected / at risk	50/164 (30.49%)	76/238 (31.93%)
Blood and lymphatic system disorders
deep venous thrombosis/pulmonary embolus ^†
# participants affected / at risk	2/164 (1.22%)	8/214 (3.74%)
# events	2	8
General disorders
death ^†
# participants affected / at risk	4/164 (2.44%)	11/214 (5.14%)
# events	4	11
other ^†
# participants affected / at risk	44/164 (26.83%)	57/214 (26.64%)
# events	44	57

†	Events were collected by systematic assessment

Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Joseph Quinn, MD
Organization: Oregon Health and Sciences University/Portland VA Medical Center, Portland, Oregon.
phone: 503-494-6976
e-mail: quinnj@ohsu.edu

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.

Publications automatically indexed to this study:

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:	May 15, 2013
Health Authority:	United States: Food and Drug Administration

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