Clinical trial NCT00539305: Hormone and Information Processing Study
Official title: Testosterone Supplementation in Men With MCI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mild Cognitive Impairment
Alzheimer's Disease
Keywords: selective androgen receptor modulators (SARMs)
hormone replacement therapy
age-associated cognitive decline
testosterone supplementation
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: Solvay Pharmaceuticals
First posted: 2007-10-04
Enrollment: 22
Sex: MALE
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Behavioral & Mood Measure: Profile of Mood States (POMS)
timeFrame: Baseline, 3 and 6 months
measure: Cognitive Changes Measured by Neuropsychological Tests: Rey Auditory Verbal Learning Test
timeFrame: Baseline, 3 and 6 months
measure: Geriatric Depression Scale (GDS)
timeFrame: Baseline, Month 3, Month 6
measure: Short-Form Health Survey (SF-36)
timeFrame: Baseline, Month 3, Month 6
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care Systems
state: Washington
Study officials:
affiliation: University of Washington
name: Monique Cherrier, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cherrier MM, Asthana S, Plymate S, Baker L, Matsumoto AM, Peskind E, Raskind MA, Brodkin K, Bremner W, Petrova A, LaTendresse S, Craft S. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology. 2001 Jul 10;57(1):80-8. doi: 10.1212/wnl.57.1.80.
citation: Cherrier MM, Matsumoto AM, Amory JK, Ahmed S, Bremner W, Peskind ER, Raskind MA, Johnson M, Craft S. The role of aromatization in testosterone supplementation: effects on cognition in older men. Neurology. 2005 Jan 25;64(2):290-6. doi: 10.1212/01.WNL.0000149639.25136.CA.
citation: Cherrier MM, Matsumoto AM, Amory JK, Asthana S, Bremner W, Peskind ER, Raskind MA, Craft S. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology. 2005 Jun 28;64(12):2063-8. doi: 10.1212/01.WNL.0000165995.98986.F1.
citation: Cherrier MM, Matsumoto AM, Amory JK, Johnson M, Craft S, Peskind ER, Raskind MA. Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men. Psychoneuroendocrinology. 2007 Jan;32(1):72-9. doi: 10.1016/j.psyneuen.2006.10.008. Epub 2006 Dec 4.
citation: Lu PH, Masterman DA, Mulnard R, Cotman C, Miller B, Yaffe K, Reback E, Porter V, Swerdloff R, Cummings JL. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol. 2006 Feb;63(2):177-85. doi: 10.1001/archneur.63.2.nct50002. Epub 2005 Dec 12.