Treated Hypertension
Conditions
Keywords
Hypertension, Vascular Risk, Alzheimer's Risk, fish oil, Lipoic acid
Brief summary
The primary aim of the pilot study is to provide data that can be used to better determine sample size for the design of a larger clinical trial. The pilot will evaluate the effectiveness of Lipoic Acid (LA) plus Omega-3 fatty acids (Omega-3) on preventing Alzheimer's Disease (AD). The investigators will also collect data to evaluate recruitment rate, safety, and compliance over the 12 month study period.
Detailed description
The primary aim is to collect data so that we can determine effect size between lipoic acid plus omega-3 fatty acids and placebo on the primary outcome measure Trails B (executive function). This is designed as a pilot randomized, double-blind, placebo-controlled study with a 12 month intervention period. Thirty participants diagnosed with hypertension that is treated (systolic blood pressure 90-160 mm Hg, diastolic blood pressure 60-90 mm Hg) that have low omega-3 fatty acid levels, and normal cognitive function will be randomized to receive study drug or placebo.
Interventions
DRUGLipoic Acid plus Omega-3 Fatty Acids
alpha lipoic acid (racemic) and fish oil concentrate
DRUGPlacebo
placebo capsules
Sponsors
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 55 years or older * Non-demented: Montreal Cognitive Assessment \> 26 and Clinical Dementia Rating = 0 * Diagnosis of Essential Hypertension with systolic 90-160 mm Hg and diastolic 60-90 mm Hg * Stable dose of antihypertensive medication 4 month prior to study enrollment * Stable dose of lipid lowering medication - dose must be stable for 4 months prior to study enrollment * Low Omega-3 fatty acid Status: Omega-3 index, \< 4% of total fatty acid of combined docosahexaenoic acid and eicosapentanoic acid * Geriatric Depression Scale \< 5 * General health status that will not interfere with the participant's ability to complete the study. * Screening laboratory values within normal limits or, if abnormal, deemed clinically insignificant by the investigator * Sufficient English language skills to complete all testing
Exclusion criteria
* Alzheimer's, Dementia or other neurodegenerative disease. * 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) * Insulin dependent diabetes or uncontrolled diabetes (diabetes controlled on medications other than insulin are acceptable) * Fish intake of one 6 ounce serving \> once a week less than 4 months prior to enrollment * Omega-3 fatty acid supplement intake (e.g. fish oil capsules, cod liver oil) less than 4 months prior to enrollment * Lipoic Acid supplementation less than 1 month prior to enrollment * Taking systemic corticosteroids, neuroleptics, antiparkinsonian agents, and/or narcotic analgesics. Low dose sinemet and dopamine agonist taken once a day for restless leg syndrome is not an exclusion. * Contraindications to MRI, including: subjects with intrathecal pumps, stimulators, pacemakers, aneurysm clips, non-removable hearing aids, or metal fragments in the eyes. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trails Making Test Part B (Executive Function) | Baseline, 6 months, and 12 months | The trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1 - 13) and letters (A - L); as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient should be instructed to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Time the patient as he or she connects the trail. If the patient makes an error, point it out immediately and allow the patient to correct it. Results for part B are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment. |
Secondary
| Measure | Time frame |
|---|---|
| White Matter Hyperintensity Volume (Brain MRI) | Baseline and 12 months |
Countries
United States
Participant flow
Pre-assignment details
Med exclusions included Omega-3 fatty acid supplement intake \< 4 months prior to enrollment; Lipoic acid supplementation \< 1 month prior to enrollment; stable dosage for 4 months prior to enrollment of antihypertensive medication and (if prescribed) lipid lowering medication. Other exclusions included labs and test scores out of range.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Lipoic Acid plus Omega-3 Fatty Acids: alpha lipoic acid (racemic) and fish oil concentrate | 21 |
| Lipoic Acid Plus Omega-3 Fatty Acids Lipoic Acid plus Omega-3 Fatty Acids: alpha lipoic acid (racemic) and fish oil concentrate | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Lipoic Acid Plus Omega-3 Fatty Acids | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.38 years STANDARD_DEVIATION 5.84 | 66.05 years STANDARD_DEVIATION 8.19 | 65.71 years STANDARD_DEVIATION 7.03 |
| Apo E4 Carrier No | 13 Participants | 15 Participants | 28 Participants |
| Apo E4 Carrier Yes | 7 Participants | 5 Participants | 12 Participants |
| Arachidonic Acid (AA) | 10.64 % composition of blood STANDARD_DEVIATION 1.56 | 9.33 % composition of blood STANDARD_DEVIATION 1.4 | 9.98 % composition of blood STANDARD_DEVIATION 1.61 |
| Diastolic BP | 77.05 mmHg STANDARD_DEVIATION 9.76 | 74.29 mmHg STANDARD_DEVIATION 10.79 | 75.67 mmHg STANDARD_DEVIATION 10.26 |
| Docosahexaenoic Acid (DHA) | 2.53 % composition of blood STANDARD_DEVIATION 0.59 | 2.62 % composition of blood STANDARD_DEVIATION 1.01 | 2.58 % composition of blood STANDARD_DEVIATION 0.82 |
| Education Completed college | 7 Participants | 5 Participants | 12 Participants |
| Education High school or less | 1 Participants | 4 Participants | 5 Participants |
| Education Masters/Graduate School | 11 Participants | 10 Participants | 21 Participants |
| Education Some college | 2 Participants | 2 Participants | 4 Participants |
| Eicosapentaenoic Acid (EPA) | 0.62 % composition of blood STANDARD_DEVIATION 0.19 | 0.84 % composition of blood STANDARD_DEVIATION 0.41 | 0.73 % composition of blood STANDARD_DEVIATION 0.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 20 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Exercise Doesn't exercise | 2 Participants | 3 Participants | 5 Participants |
| Exercise Exercises 2+ times/week | 15 Participants | 14 Participants | 29 Participants |
| Exercise Some exercise | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 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 | 18 Participants | 20 Participants | 38 Participants |
| Sex: Female, Male Female | 10 Participants | 17 Participants | 27 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 15 Participants |
| Smoking Former smoker | 9 Participants | 10 Participants | 19 Participants |
| Smoking Non-smoker | 11 Participants | 10 Participants | 21 Participants |
| Smoking Smoker | 0 Participants | 0 Participants | 0 Participants |
| Systolic BP | 141.67 mmHg STANDARD_DEVIATION 14.64 | 131.76 mmHg STANDARD_DEVIATION 15.77 | 136.71 mmHg STANDARD_DEVIATION 15.84 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 21 | 17 / 21 |
| serious Total, serious adverse events | 3 / 21 | 1 / 21 |
Outcome results
Primary
Trails Making Test Part B (Executive Function)
The trail Making Test consist of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1 - 13) and letters (A - L); as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient should be instructed to connect the circles as quickly as possible, without lifting the pen or pencil from the paper. Time the patient as he or she connects the trail. If the patient makes an error, point it out immediately and allow the patient to correct it. Results for part B are reported as the number of seconds required to complete the task; therefore, higher scores reveal greater impairment.
Time frame: Baseline, 6 months, and 12 months
Population: Not all tests were completed by all randomized subjects due to missed visits and/or discontinuations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Trails Making Test Part B (Executive Function) | Baseline | 69.57 time to completion (seconds) | Standard Deviation 19.15 |
| Placebo | Trails Making Test Part B (Executive Function) | 6 Months | 62.53 time to completion (seconds) | Standard Deviation 16.59 |
| Placebo | Trails Making Test Part B (Executive Function) | 12 Months | 69.75 time to completion (seconds) | Standard Deviation 20.79 |
| Lipoic Acid Plus Omega-3 Fatty Acids | Trails Making Test Part B (Executive Function) | Baseline | 81.59 time to completion (seconds) | Standard Deviation 53.08 |
| Lipoic Acid Plus Omega-3 Fatty Acids | Trails Making Test Part B (Executive Function) | 6 Months | 69.25 time to completion (seconds) | Standard Deviation 20.55 |
| Lipoic Acid Plus Omega-3 Fatty Acids | Trails Making Test Part B (Executive Function) | 12 Months | 71.10 time to completion (seconds) | Standard Deviation 32.77 |
Secondary
White Matter Hyperintensity Volume (Brain MRI)
Time frame: Baseline and 12 months
Population: At baseline, 4 participants either could not complete the MRI or the MRI could not be analyzed due to quality; at 12 months, 13 participants either discontinued, could not complete the MRI, or did not complete the baseline and therefore were not scanned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | White Matter Hyperintensity Volume (Brain MRI) | Baseline | 6.13 cubic centimeters | Standard Deviation 11.91 |
| Placebo | White Matter Hyperintensity Volume (Brain MRI) | 12 Months | 5.14 cubic centimeters | Standard Deviation 13.04 |
| Lipoic Acid Plus Omega-3 Fatty Acids | White Matter Hyperintensity Volume (Brain MRI) | Baseline | 5.31 cubic centimeters | Standard Deviation 7.37 |
| Lipoic Acid Plus Omega-3 Fatty Acids | White Matter Hyperintensity Volume (Brain MRI) | 12 Months | 5.07 cubic centimeters | Standard Deviation 7.01 |