Hormone and Information Processing Study

Mild Cognitive Impairment Clinical Trial

— HIP  

Official title:

Testosterone Supplementation in Men With MCI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00539305
• Other study ID #: 29975-A
• Secondary ID: R01AG0271561R01A
• Status: Completed
• Phase: Phase 3
• First received: October 3, 2007
• Last updated: July 10, 2014
• Start date: July 2009
• Est. completion date: May 2012

Study information

• Verified date: July 2014
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: May 2012
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 60 Years to 90 Years

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognition Disorders
• Mild Cognitive Impairment

Intervention

Drug:
• testosterone gel
50-100mg applied topically daily for six months
• placebo gel
applied topically daily for six months

Locations

Country	Name	City	State
United States	VA Puget Sound Health Care Systems	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
University of Washington	National Institute on Aging (NIA), Solvay Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View 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. — View 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. — View 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. Epub 2006 Dec 4. — View 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. Epub 2005 Dec 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, 3 and 6 months	No
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.	Baseline, 3 and 6 months	No
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.	Baseline, Month 3, Month 6	No
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.	Baseline, Month 3, Month 6	No