Hormone and Information Processing Study

Phase 3

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Study drug; testosterone transdermal gel	testosterone gel	Dose will be adjusted as needed to maintain a target total T level of 500-900 ng/dl
2	placebo gel	-

Primary Outcome Measures

Name	Time	Method
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.
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.
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.
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.

Secondary Outcome Measures

Name	Time	Method

Locations (1): VA Puget Sound Health Care Systems
🇺🇸
Seattle, Washington, United States