Lipoic Acid and Omega-3 Fatty Acids for Alzheimer's Disease

• ClinicalTrials.gov Identifier: NCT01058941
• Recruitment Status: Completed
• First Posted: January 29, 2010
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017
• Sponsor: Oregon Health and Science University
• Information provided by (Responsible Party): Lynne Shinto, Oregon Health and Science University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer's Disease
• Interventions: Drug: Lipoic acid and fish oil concentrate; Drug: Placebo
• Enrollment: 67

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Lipoic Acid and Omega-3 Fatty Acids	Placebo
Arm/Group Description	lipoic acid and fish oil concentrate lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months	placebo lipoic acid plus placebo oil lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months
Period Title: Overall Study
Started	34	33
Completed	25	22
Not Completed	9	11

Baseline Characteristics

Arm/Group Title		Lipoic Acid and Omega-3 Fatty Acids	Placebo	Total
Arm/Group Description		lipoic acid and fish oil concentrate lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months	placebo lipoic acid plus placebo oil lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months	Total of all reporting groups
Overall Number of Baseline Participants		34	33	67
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	33 participants	67 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	5 14.7%	4 12.1%	9 13.4%
	>=65 years	29 85.3%	29 87.9%	58 86.6%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	34 participants	33 participants	67 participants
		73.3; (56 to 92)	76.2; (52 to 89)	74.7; (52 to 92)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	33 participants	67 participants
	Female	18 52.9%	17 51.5%	35 52.2%
	Male	16 47.1%	16 48.5%	32 47.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	33 participants	67 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	34 100.0%	32 97.0%	66 98.5%
	Unknown or Not Reported	0 0.0%	1 3.0%	1 1.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	33 participants	67 participants
	American Indian or Alaska Native	0 0.0%	1 3.0%	1 1.5%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 2.9%	1 3.0%	2 3.0%
	White	33 97.1%	30 90.9%	63 94.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	1 3.0%	1 1.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	34 participants	33 participants	67 participants
		34	33	67

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Activities of Daily Living (ADL) at 18 Months
Description	The Alzheimer's Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL) is used to assess activities of daily living in people with AD using a structured interview to ask the AD participant's caregiver/study partner to assess functional ability over a wide range of performance measures. A higher ADL score indicates greater impairment in functional ability; scores range from 0 to 27.
Time Frame	Baseline and 18 months

Outcome Measure Data

Analysis Population Description

Twenty participants discontinued from the study prior to completing all study visits. One treatment participant did not complete the final ADL assessment.

Arm/Group Title	Lipoic Acid and Omega-3 Fatty Acids	Placebo
Arm/Group Description:	lipoic acid and fish oil concentrate lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months	placebo lipoic acid plus placebo oil lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months
Overall Number of Participants Analyzed	24	22
Mean (Standard Deviation); Unit of Measure: units on a scale
	-11.58 (12.68)	-13.45 (12.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoic Acid and Omega-3 Fatty Acids, Placebo
	Comments	The target enrollment was 60 subjects, allowing for up to a 20% drop-out. It was calculated that with 48 subjects (24 per group) we would have 80% power to see differences in ADL scores over 18 months between the treatment and placebo groups with a significance level of 0.025 based on a simple Bonferroni adjustment, since we had two primary outcomes.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.82
	Comments	We used a significance level of p = 0.025 for our measure of ADL changes based on a simple Bonferroni adjustment since we have two primary outcomes.
	Method	Mixed Models Analysis
	Comments	Adjusted for baseline outcome, time from baseline, age, education category, BMI, cholinesterase inhibitors, memantine, vitamin E, and Apo-E.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -3.97 to 3.13
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 18 Months
Description	The ADAS-cog assesses general cognitive function over multiple domains and evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates greater impairment on a range of scores from 0 to 70. A total score of 70 indicates maximum severity.
Time Frame	Baseline and 18 months

Outcome Measure Data

Analysis Population Description

Twenty participants discontinued from the study prior to completing all study visits. One placebo and one treatment participant did not complete the final ADAS-cog assessment.

Arm/Group Title	Lipoic Acid and Omega-3 Fatty Acids	Placebo
Arm/Group Description:	lipoic acid and fish oil concentrate lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months	placebo lipoic acid plus placebo oil lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months
Overall Number of Participants Analyzed	24	21
Mean (Standard Deviation); Unit of Measure: units on a scale
	6.61 (6.67)	3.40 (4.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lipoic Acid and Omega-3 Fatty Acids, Placebo
	Comments	The target enrollment was 60 subjects, allowing for up to a 20% drop-out. It was calculated that with 48 subjects (24 per group) we would have 80% power to see differences in ADL scores over 18 months between the treatment and placebo groups with a significance level of 0.025 based on a simple Bonferroni adjustment, since we had two primary outcomes.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.001
	Comments	We used a significance level of p = 0.025 for our measure of ADAS-cog changes based on a simple Bonferroni adjustment since we have two primary outcomes.
	Method	Mixed Models Analysis
	Comments	Adjusted for baseline outcome, time from baseline, age, education category, BMI, cholinesterase inhibitors, memantine, vitamin E, and Apo-E.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.68
	Confidence Interval	(2-Sided) 95%; -5.90 to -1.46
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events (AEs) were monitored once a month as a part of the clinic visits and monthly by phone. Reported AEs include events that occurred on or after Day 0 and on or before month 18.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Lipoic Acid and Omega-3 Fatty Acids		Placebo
Arm/Group Description	lipoic acid and fish oil concentrate lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months		placebo lipoic acid plus placebo oil lipoic acid and fish oil concentrate: lipic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months
All-Cause Mortality
	Lipoic Acid and Omega-3 Fatty Acids		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/34 (2.94%)		2/33 (6.06%)
Serious Adverse Events
	Lipoic Acid and Omega-3 Fatty Acids		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/34 (29.41%)		7/33 (21.21%)
Cardiac disorders
Tachycardia † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Atrial fibrillation † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Gastrointestinal disorders
Gastrointestinal obstruction † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Gastric ulcer haemorrhage † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
General disorders
Medical device complication † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Infections and infestations
Pneumonia † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1 [1]	0/34 (0.00%)	0	1/33 (3.03%)	1
Head injury † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Metabolism and nutrition disorders
Abnormal loss of weight † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia † 1	0/34 (0.00%)	0	1/33 (3.03%)	1
Laryngeal cancer † 1	0/34 (0.00%)	0	1/33 (3.03%)	1
Nervous system disorders
Dementia Alzheimer's Type † 1 [2]	2/34 (5.88%)	2	0/33 (0.00%)	0
Thrombotic cerebral infarction † 1	0/34 (0.00%)	0	1/33 (3.03%)	1
Cerebrovascular accident † 1	1/34 (2.94%)	1	1/33 (3.03%)	1
Psychiatric disorders
Drug-induced delirium † 1 [3]	0/34 (0.00%)	0	1/33 (3.03%)	1
Renal and urinary disorders
Acute kidney injury † 1	0/34 (0.00%)	0	1/33 (3.03%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory tract infection † 1	0/34 (0.00%)	0	1/33 (3.03%)	1
Pleural effusion † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
Surgical and medical procedures
Subdural haematoma evacuation † 1	1/34 (2.94%)	1	0/33 (0.00%)	0
1 Term from vocabulary, MedDRA (Unspecified); † Indicates events were collected by systematic assessment; [1] Fall down stairs; [2] Rapid cognitive decline; [3] Nyquil use
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lipoic Acid and Omega-3 Fatty Acids		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/34 (85.29%)		27/33 (81.82%)
Blood and lymphatic system disorders
Anemia † 1	2/34 (5.88%)	2	3/33 (9.09%)	3
Gastrointestinal disorders
Nausea † 1	4/34 (11.76%)	6	5/33 (15.15%)	6
Diarrhea † 1	1/34 (2.94%)	1	7/33 (21.21%)	8
Vomiting † 1	3/34 (8.82%)	4	3/33 (9.09%)	4
Abdominal pain † 1	3/34 (8.82%)	3	2/33 (6.06%)	2
General disorders
Fatigue † 1	4/34 (11.76%)	4	1/33 (3.03%)	1
Immune system disorders
Allergic conditions † 1	4/34 (11.76%)	4	0/33 (0.00%)	0
Injury, poisoning and procedural complications
Fall † 1	4/34 (11.76%)	4	3/33 (9.09%)	3
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/34 (2.94%)	1	4/33 (12.12%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer † 1	2/34 (5.88%)	3	3/33 (9.09%)	4
Nervous system disorders
Dizziness † 1	3/34 (8.82%)	3	4/33 (12.12%)	4
Headache/Migraine † 1	5/34 (14.71%)	6	0/33 (0.00%)	0
Psychiatric disorders
Depression † 1	2/34 (5.88%)	2	3/33 (9.09%)	3
Behavioral and psychiatric symptoms of dementia † 1	4/34 (11.76%)	5	0/33 (0.00%)	0
Renal and urinary disorders
Urinary tract infection † 1	1/34 (2.94%)	1	2/33 (6.06%)	3
Urinary incontinence † 1	2/34 (5.88%)	2	2/33 (6.06%)	2
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection † 1	5/34 (14.71%)	7	7/33 (21.21%)	7
Vascular disorders
Sycope † 1	2/34 (5.88%)	3	1/33 (3.03%)	1
1 Term from vocabulary, MedDRA (Unspecified); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

Results Point of Contact

• Name/Title: Dr. Lynne Shinto, ND, MPH
• Organization: Oregon Health & Science University
• Phone: 503-494-5035
• EMail: shintol@ohsu.edu

• Responsible Party: Lynne Shinto, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01058941
• Other Study ID Numbers: R01AG033613-01A1 ( U.S. NIH Grant/Contract )
• First Submitted: January 27, 2010
• First Posted: January 29, 2010
• Results First Submitted: March 1, 2017
• Results First Posted: April 13, 2017
• Last Update Posted: April 13, 2017