Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease, fish oil, lipoic acid
Brief summary
The purpose of this study was to see if taking lipoic acid plus omega-3 fatty acids (omega-3s) can slow the Alzheimer's disease (AD) process. To see if the treatment can slow the AD process, the investigators looked at changes in memory and changes in a person's daily activities over 18 months.
Detailed description
Current pharmacological agents for AD have had no impact on disease prevalence and have had limited effects on improving the clinical course of AD. The exponential rise in the prevalence, incidence, and cost of care for AD make finding therapeutic agents that can either prevent AD or delay disease progression an urgent health care need. Since inflammation, lipid dysregulation, and insulin resistance have each been associated with AD pathology, the combination of lipoic acid plus fish oil has the potential to maximize therapeutic benefit by acting on all three mechanisms associated with disease pathology.
Interventions
DRUGLipoic acid and fish oil concentrate
Lipoic acid (600 milligrams per day) and fish oil concentrate (3 grams per day) for 18 months
DRUGPlacebo
Placebo LA and placebo oil capsules for 18 months
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 55 years or older 2. Probable AD by National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association - NINCDS/ADRDA criteria 3. MMSE between 15-26 4. Caregiver/study partner that can accompany participant to all study visits 5. Stable use of cholinesterase inhibitors and memantine permitted - doses must be stable for 4 months prior to study enrollment 6. Stable doses of over-the-counter antioxidants (e.g. vitamin E, ginkgo biloba) are permitted - dose must be stable for 4 months prior to study enrollment 7. Stable dose of lipid lowering medication - dose must be stable for 4 months prior to study enrollment 8. Geriatric Depression Scale (GDS) - Score of \< 5 9. General health status that will not interfere with the participant's ability to complete the study. 10. Screening laboratory values within normal limits or, if abnormal, deemed clinically insignificant by the investigator 11. Sufficient English language skills to complete all testing
Exclusion criteria
1. Non-AD dementia 2. Residence in nursing home facility at screening visit (residence in community assisted living and long-term care facilities in which the participant still performs majority of basic activities of daily living will not be an exclusion) 3. History of clinically significant stroke (stroke with neurologic deficits \> 6 months after diagnosis) 4. Health conditions such as cancer diagnosed \< 5 years prior to enrollment (prostate cancer gleason grade \< 3 and non metastatic skin cancers are acceptable), liver disease, history of ventricular fibrillation or ventricular tachycardia, major psychiatric disorder, central nervous system diseases (e.g. brain tumor, seizure disorder) 5. Insulin dependent diabetes or uncontrolled diabetes (diabetes controlled on medications other than insulin are acceptable) 6. Hyperlipidemic (triglycerides \>500 mg/dl, LDL \> 160 mg/dl, total cholesterol \>240 mg/dl). LDL levels between 160 mg/dl and 165 mg/dl will be reviewed by the PI and included if judged to be safe. Patients who have a history or hyperlipidemia, but are not taking lipid-lowering medications due to potential memory impairment side effects will be reviewed on a case-by-case basis by the PI and enrolled in the study if deemed safe by PI and the patient's primary care provider. 7. Fish intake of one 6 ounce serving \> once a week less than 4 months prior to enrollment 8. Omega-3 fatty acid supplement intake (e.g. fish oil capsules, cod liver oil, or flaxseed oil) less than 4 months prior to enrollment 9. Lipoic Acid supplementation less than 1 month prior to enrollment 10. Taking systemic corticosteroids, neuroleptics, antiparkinsonian agents, and narcotic analgesics. Certain low dose antipsychotic use will be reviewed by the principle investigator on a case-by-case basis and may be allowed if determined that dose is not strong enough to affect performance on cognitive evaluations. Low dose sinemet and dopamine agonist taken once a day for restless leg syndrome is not an exclusion. 11. Contraindications to MRI (for subjects enrolled at Bend, Medford, and Klamath sites that decide not to undergo MRI, this will not be an exclusion). 12. Enrollment in another study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Activities of Daily Living (ADL) at 18 Months | Baseline and 18 months | 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. |
| Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 18 Months | Baseline and 18 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lipoic Acid and Omega-3 Fatty Acids 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 | 34 |
| Placebo 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 | 33 |
| Total | 67 |
Baseline characteristics
| Characteristic | Lipoic Acid and Omega-3 Fatty Acids | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 29 Participants | 29 Participants | 58 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 4 Participants | 9 Participants |
| Age, Continuous | 73.3 years | 76.2 years | 74.7 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 32 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 33 Participants | 30 Participants | 63 Participants |
| Region of Enrollment United States | 34 participants | 33 participants | 67 participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 35 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 34 | 2 / 33 |
| other Total, other adverse events | 29 / 34 | 27 / 33 |
| serious Total, serious adverse events | 10 / 34 | 7 / 33 |
Outcome results
Primary
Change From Baseline in Activities of Daily Living (ADL) at 18 Months
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
Population: Twenty participants discontinued from the study prior to completing all study visits. One treatment participant did not complete the final ADL assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipoic Acid and Omega-3 Fatty Acids | Change From Baseline in Activities of Daily Living (ADL) at 18 Months | -11.58 units on a scale | Standard Deviation 12.68 |
| Placebo | Change From Baseline in Activities of Daily Living (ADL) at 18 Months | -13.45 units on a scale | Standard Deviation 12.89 |
Comparison: 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.p-value: 0.8295% CI: [-3.97, 3.13]Mixed Models Analysis
Primary
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 18 Months
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lipoic Acid and Omega-3 Fatty Acids | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 18 Months | 6.61 units on a scale | Standard Deviation 6.67 |
| Placebo | Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) at 18 Months | 3.40 units on a scale | Standard Deviation 4.5 |
Comparison: 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.p-value: 0.00195% CI: [-5.9, -1.46]Mixed Models Analysis