Hormone and Information Processing Study

NCT ID: NCT00539305

Last Updated: 2014-07-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2012-05-31

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.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Study drug; testosterone transdermal gel

Dose will be adjusted as needed to maintain a target total T level of 500-900 ng/dl

Group Type: EXPERIMENTAL

testosterone gel

Intervention Type: DRUG

50-100mg applied topically daily for six months

2

Group Type: PLACEBO_COMPARATOR

placebo gel

Intervention Type: DRUG

applied topically daily for six months

Interventions

testosterone gel

50-100mg applied topically daily for six months

Intervention Type: DRUG

placebo gel

applied topically daily for six months

Intervention Type: DRUG

Other Intervention Names

Solvay Testosterone Gel

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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Solvay Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Monique Cherrier

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Monique Cherrier, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

VA Puget Sound Health Care Systems

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 11445632 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15668427 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15985573 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17145137 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16344336 (View on PubMed)

Other Identifiers

R01AG027156

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01AG027156-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

29975-A

Identifier Type: -

Identifier Source: org_study_id