Alzheimer's Disease, Oxidative Stress, Dementia, Hyperlipidemia, Inflammation
Conditions
Keywords
Fish Oils, Thioctic Acid, Antioxidants, Dietary Supplements
Brief summary
The purpose of this study is to determine the effect of fish oil and the antioxidant alpha lipoic acid on factors in the blood that are associated with the progression of Alzheimer's Disease (AD).
Detailed description
Alzheimer's disease (AD) is a serious condition associated with increased inflammation, cholesterol, and oxidative stress (a condition involving an excess of free radicals and a decrease in antioxidant levels). Fish oil and alpha lipoic acid, which have few side effects, may help relieve these problems; therefore, these supplements may slow the progression of AD, particularly when given in combination. This study will evaluate the effect of fish oil and alpha lipoic acid on inflammation, lipid levels, and oxidative stress. Participants in this study will be randomly assigned to receive fish oil alone, fish oil and alpha lipoic acid, or placebo for 1 year. AD rating scales as well as urine and blood tests will be used to assess participants. Participants will have monthly clinic visits during the study to monitor adverse events and to undergo various laboratory tests.
Interventions
DIETARY_SUPPLEMENTFish Oil
Fish oil capsule
DIETARY_SUPPLEMENTLipoic Acid
Lipoic acid capsule
OTHERFish Oil Placebo
Soybean oil placebo capsule
OTHERLipoic Acid Placebo
Lipoic acid (LA) placebo capsule containing no LA
Sponsors
National Institute on Aging (NIA)
National Center for Research Resources (NCRR)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of probable Alzheimer's Disease or mild cognitive impairment * Mini Mental State Examination (MMSE) score between 18 and 26 * Clinical Dementia Rating (CDR) of 0.5 or 1.0 * Fluent in English
Exclusion criteria
* Use of lipid lowering medications * Consumption of fish of more than twice a week * Use of omega and alpha lipoic acid supplements * Use of systemic corticosteroids, neuroleptics, anti-Parkinsonian agents, or narcotic analgesics * Depression * Any other serious health conditions that may interfere with the study * Enrollment in another clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| F2-isoprostane Level Urine F2-Isoprostanes | baseline, 12 months | F2-isoprostane is a biomarker was used as an effective indicator for detecting a decrease in systemic oxidative damage (oxidative damage in lipids). Urine F2-Isoprostanes were used to avoid ex vivo lipid peroxidation that can occur with plasma samples. |
| Change in Mini-Mental State Exam (MMSE) Score From Baseline to 12 Months | baseline, 12 months | The MMSE is a measure of global cognitive function, and scores range from 0-30, with a lower score indicates greater cognitive impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) Scores From Baseline to 12 Months | baseline, 12 months | The Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) measures an individual's ability to carry out tasks that are important for daily living and capture functional changes. Scores for each question range from 0 (no assistance needed) to 2 (full assistance needed), and were assessed by informant interview. The combination of scores for ADL (ranging from 0-18) and IADL (0-14) is the outcome (0-32), with higher scores indicating lesser ability to carry out daily living tasks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo oil (soybean oil), daily dose 3 grams taken for 12 months | 13 |
| Fish Oil Fish oil concentrate, daily dose 3 grams per day containing 675 mg docosahexaenoic acid and 975 mg eicosapentanoic acid, taken for 12 months. | 13 |
| Fish Oil Plus Lipoic Acid Fish oil concentrate, daily dose 3 grams per day containing 675 mg docosahexaenoic acid and 975 mg eicosapentanoic acid plus alpha lipoic acid (racemic) daily dose 600 mg taken for 12 months. | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | stopped taking study medication | 1 | 0 | 1 |
| Overall Study | subject moved | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Fish Oil Plus Lipoic Acid | Total | Placebo | Fish Oil |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 10 Participants | 33 Participants | 11 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 2 Participants | 1 Participants |
| Age, Continuous | 76.7 years STANDARD_DEVIATION 10.6 | 75.9 years STANDARD_DEVIATION 9.7 | 75.2 years STANDARD_DEVIATION 10.8 | 75.9 years STANDARD_DEVIATION 8.1 |
| Region of Enrollment United States | 13 participants | 39 participants | 13 participants | 13 participants |
| Sex: Female, Male Female | 6 Participants | 21 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 7 Participants | 18 Participants | 6 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 13 | 5 / 13 | 7 / 13 |
| serious Total, serious adverse events | 1 / 13 | 1 / 13 | 0 / 13 |
Outcome results
Primary
Change in Mini-Mental State Exam (MMSE) Score From Baseline to 12 Months
The MMSE is a measure of global cognitive function, and scores range from 0-30, with a lower score indicates greater cognitive impairment.
Time frame: baseline, 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Mini-Mental State Exam (MMSE) Score From Baseline to 12 Months | -4.64 units on a scale | Standard Deviation 4.65 |
| Fish Oil | Change in Mini-Mental State Exam (MMSE) Score From Baseline to 12 Months | -4.27 units on a scale | Standard Deviation 4.15 |
| Fish Oil Plus Lipoic Acid | Change in Mini-Mental State Exam (MMSE) Score From Baseline to 12 Months | -1.00 units on a scale | Standard Deviation 2.3 |
Primary
F2-isoprostane Level Urine F2-Isoprostanes
F2-isoprostane is a biomarker was used as an effective indicator for detecting a decrease in systemic oxidative damage (oxidative damage in lipids). Urine F2-Isoprostanes were used to avoid ex vivo lipid peroxidation that can occur with plasma samples.
Time frame: baseline, 12 months
Population: intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | F2-isoprostane Level Urine F2-Isoprostanes | 0.40 nanogram per miligram | Standard Deviation 1.1 |
| Fish Oil | F2-isoprostane Level Urine F2-Isoprostanes | -2.02 nanogram per miligram | Standard Deviation 3.3 |
| Fish Oil Plus Lipoic Acid | F2-isoprostane Level Urine F2-Isoprostanes | 0.45 nanogram per miligram | Standard Deviation 0.53 |
p-value: 0.83Regression, Linear
Secondary
Change in Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) Scores From Baseline to 12 Months
The Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) measures an individual's ability to carry out tasks that are important for daily living and capture functional changes. Scores for each question range from 0 (no assistance needed) to 2 (full assistance needed), and were assessed by informant interview. The combination of scores for ADL (ranging from 0-18) and IADL (0-14) is the outcome (0-32), with higher scores indicating lesser ability to carry out daily living tasks.
Time frame: baseline, 12 months
Population: In the placebo group there were 2 discontinuations (1 moved, 1 death). In the fish oil group there were 2 discontinuations (1 discontinue, 1 death). In the fish oil and lipoic acid group there was 1 discontinuation (due to meds). These discontinuations did not complete the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) Scores From Baseline to 12 Months | 4.2 units on a scale | Standard Error 0.9 |
| Fish Oil | Change in Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) Scores From Baseline to 12 Months | 0.7 units on a scale | Standard Error 1 |
| Fish Oil Plus Lipoic Acid | Change in Activities of Daily Living/Instrumental Activities of Daily Living (ADL/IADL) Scores From Baseline to 12 Months | 0.9 units on a scale | Standard Error 1.1 |