Alzheimer's Disease, Mild Cognitive Impairment
Conditions
Keywords
selective androgen receptor modulators (SARMs), hormone replacement therapy, age-associated cognitive decline, testosterone supplementation
Brief summary
The purpose of this study is to examine the effects of testosterone (T) replacement on changes in thinking and memory, as well as mood in older men with mild cognitive impairment (MCI) and low T levels. The study will also examine whether taking testosterone has effects on biological markers related to Alzheimer's disease.
Detailed description
Natural age related declines in testosterone (T) are associated with decreases in cognitive abilities independent of health status. Low T levels over time are associated with increased risk for developing Alzheimer's disease (AD). These findings suggest that men with low T levels are most at risk for age-related cognitive decline and AD and therefore most likely to benefit from T supplementation to prevent the development of AD or age-associated cognitive decline. The current study will assess cognition, mood, and cerebral spinal fluid (CSF) biomarker response to T supplementation in older men with mild cognitive impairment (MCI) and low T levels. Participants will be randomized to either receive T treatment or a placebo for six months. Participants will come in for about five visits within the span of six months where they will complete cognitive & memory tests, fill out mood questionnaires, and have their blood drawn to monitor the medication level. A sample of blood will also be taken at one visit to test for apolipoprotein E (APOE), which is a genetic risk factor associated with AD. Participants will have the option to get a spinal tap in order to measure biological markers associated with Alzheimer's disease including beta-amyloid 1-40, 42, total-tau, and phosphorylated-tau-181-231. This will require an additional two visits.
Interventions
DRUGtestosterone gel
50-100mg applied topically daily for six months
DRUGplacebo gel
applied topically daily for six months
Sponsors
National Institute on Aging (NIA)
Solvay Pharmaceuticals
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
60 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Male 60-90 years of age * Diagnosis of mild cognitive impairment (MCI) * Low testosterone level * Primary language is English * Availability of an informant who knows the participant well enough to answer questions * Stable medications for the previous 3 months * Normal complete blood count (CBC), and no clinically significant blood chemistry * American Urological Association (AUA) symptom score less than or equal to 19 * Body Mass Index (BMI) less than 33 and stable weight in the previous year
Exclusion criteria
* Prior history of prostate cancer or prostate specific antigen level greater than 4.0ng/ml * Peripheral or vascular disease * Significant history of alcohol abuse, current alcohol abuse (more than 2 drinks per day), or other substance abuse * History of severe head injury (with loss of consciousness greater than 30 minutes) * Significant neurological illness, such as Parkinson's disease, seizure disorder, multiple sclerosis, major stoke * Smokes cigarettes * Major psychiatric illness, such as schizophrenia or bipolar disorder Prohibited Medications: * Anti-convulsants * Anti-psychotics * Sedating antihistamines * Sedative/hypnotics * Benzodiazepines * Hormone or testosterone regimens * Gonadotropin-releasing hormone (GNRH) antagonists * Flutamide * Anti-depressants and/or anti-cholinesterase inhibitors, but acceptable if on stable dose for 3 months or more
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Behavioral & Mood Measure: Profile of Mood States (POMS) | Baseline, 3 and 6 months | Values represent self evaluation of vigor-activity. The scale compares t-scores of participants to published norms (range 0-100), and higher scores indicate elevated emotion in subscale. Higher t-scores in vigor-activity subscale are considered favorable. Month 3 and Month 6 values display change from baseline. |
| Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test | Baseline, 3 and 6 months | Values represent total score in Long Delay Word List Recall. Higher score indicates higher level of functioning (range 0-15). Month 3 and Month 6 indicate change from baseline. |
| Geriatric Depression Scale (GDS) | Baseline, Month 3, Month 6 | Values represent self evaluation of depression (range 0-30). Higher scores indicate a more depressed mood. Month 3 and Month 6 indicate change from baseline. |
| Short-Form Health Survey (SF-36) | Baseline, Month 3, Month 6 | Self assessment of Physical Functioning in Health Survey. Higher scores indicate a higher level of functioning (range 0-100). Month 3 and 6 values represent change from baseline in subscale. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group Dose will be adjusted as needed to maintain a target total T level of 500-900 ng/dl
testosterone gel : 50-100mg applied topically daily for six months | 10 |
| Placebo Group Placebo gel : applied topically daily for six months | 12 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Substance Use | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo Group | Treatment Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 8 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Continuous | 70.0 years STANDARD_DEVIATION 7.7 | 71.2 years STANDARD_DEVIATION 9.1 | 70.5 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 12 participants | 10 participants | 22 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 10 | 0 / 12 |
| serious Total, serious adverse events | 0 / 10 | 0 / 12 |
Outcome results
Primary
Behavioral & Mood Measure: Profile of Mood States (POMS)
Values represent self evaluation of vigor-activity. The scale compares t-scores of participants to published norms (range 0-100), and higher scores indicate elevated emotion in subscale. Higher t-scores in vigor-activity subscale are considered favorable. Month 3 and Month 6 values display change from baseline.
Time frame: Baseline, 3 and 6 months
Population: Vigor-Activity
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group | Behavioral & Mood Measure: Profile of Mood States (POMS) | Baseline | 57.7 units on a scale | Standard Deviation 2.2 |
| Treatment Group | Behavioral & Mood Measure: Profile of Mood States (POMS) | Month 3 (Change from Baseline) | -4.5 units on a scale | Standard Deviation 2.8 |
| Treatment Group | Behavioral & Mood Measure: Profile of Mood States (POMS) | Month 6 (Change from Baseline) | 1.9 units on a scale | Standard Deviation 2.7 |
| Placebo Group | Behavioral & Mood Measure: Profile of Mood States (POMS) | Baseline | 55.5 units on a scale | Standard Deviation 2 |
| Placebo Group | Behavioral & Mood Measure: Profile of Mood States (POMS) | Month 3 (Change from Baseline) | -0.1 units on a scale | Standard Deviation 2.4 |
| Placebo Group | Behavioral & Mood Measure: Profile of Mood States (POMS) | Month 6 (Change from Baseline) | -0.5 units on a scale | Standard Deviation 2.5 |
Primary
Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test
Values represent total score in Long Delay Word List Recall. Higher score indicates higher level of functioning (range 0-15). Month 3 and Month 6 indicate change from baseline.
Time frame: Baseline, 3 and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group | Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test | Baseline | 6.2 units on a scale | Standard Deviation 1.1 |
| Treatment Group | Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test | Month 3 (Change from Baseline) | 2.3 units on a scale | Standard Deviation 0.9 |
| Treatment Group | Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test | Month 6 (Change from Baseline) | 0.9 units on a scale | Standard Deviation 0.9 |
| Placebo Group | Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test | Baseline | 4.9 units on a scale | Standard Deviation 1 |
| Placebo Group | Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test | Month 3 (Change from Baseline) | 0.0 units on a scale | Standard Deviation 0.8 |
| Placebo Group | Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test | Month 6 (Change from Baseline) | 1.5 units on a scale | Standard Deviation 0.8 |
Primary
Geriatric Depression Scale (GDS)
Values represent self evaluation of depression (range 0-30). Higher scores indicate a more depressed mood. Month 3 and Month 6 indicate change from baseline.
Time frame: Baseline, Month 3, Month 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group | Geriatric Depression Scale (GDS) | Baseline | 7.2 units on a scale | Standard Deviation 1.3 |
| Treatment Group | Geriatric Depression Scale (GDS) | Month 3 (Change from Baseline) | 0.7 units on a scale | Standard Deviation 1.5 |
| Treatment Group | Geriatric Depression Scale (GDS) | Month 6 (Change from Baseline) | -2.8 units on a scale | Standard Deviation 1.5 |
| Placebo Group | Geriatric Depression Scale (GDS) | Baseline | 4.1 units on a scale | Standard Deviation 1.2 |
| Placebo Group | Geriatric Depression Scale (GDS) | Month 3 (Change from Baseline) | 2.3 units on a scale | Standard Deviation 1.3 |
| Placebo Group | Geriatric Depression Scale (GDS) | Month 6 (Change from Baseline) | 2.7 units on a scale | Standard Deviation 2.3 |
Primary
Short-Form Health Survey (SF-36)
Self assessment of Physical Functioning in Health Survey. Higher scores indicate a higher level of functioning (range 0-100). Month 3 and 6 values represent change from baseline in subscale.
Time frame: Baseline, Month 3, Month 6
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Group | Short-Form Health Survey (SF-36) | Baseline | 70.7 units on a scale | Standard Deviation 10.4 |
| Treatment Group | Short-Form Health Survey (SF-36) | Month 3 (Change from Baseline) | 15.0 units on a scale | Standard Deviation 9.4 |
| Treatment Group | Short-Form Health Survey (SF-36) | Month 6 (Change from Baseline) | 6.4 units on a scale | Standard Deviation 8.6 |
| Placebo Group | Short-Form Health Survey (SF-36) | Baseline | 85.6 units on a scale | Standard Deviation 2.3 |
| Placebo Group | Short-Form Health Survey (SF-36) | Month 3 (Change from Baseline) | -3.8 units on a scale | Standard Deviation 6.4 |
| Placebo Group | Short-Form Health Survey (SF-36) | Month 6 (Change from Baseline) | -5.4 units on a scale | Standard Deviation 3.5 |