Androgen Effects in HIV-infected Women

Study Overview
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Brief Summary
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Androgen deficiency in HIV-infected women is associated with sarcopenia and may cause critical reductions in physical functioning and reduced bone density. The effects of long-term androgen therapy on lean body mass, bone density and other clinical endpoints including quality of life, functional status and neurocognitive function in HIV-infected women are not known.

Detailed Description
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We will perform an 18-month randomized, double-blinded, placebo-controlled study among relatively androgen deficient women with HIV, to determine the effects of testosterone administration on lean body mass. The administered dose will be 300 micrograms twice a week vs. identical placebo in the form of a transdermal preparation. Secondary endpoints include effects on bone density, quality of life, neurocognitive function and menstrual function. Open label administration at 300 micrograms twice a week will be initiated for 12 months in all subjects following the randomized portion of the study. Assuming a 15% dropout rate and 25 randomized patients, the probability is 80 percent that the study will detect a treatment difference at a two sided 5.000 percent significance level, if the true difference between the treatments is 2.7 kg. This is based on the assumption that the standard deviation of the response variable, lean body mass by DEXA, is 2.3 kg, as was shown by Choi et al1 over 12 weeks in HIV-infected women at the same dose of 300 ug 2x/week.

Official Title
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Androgen Effects in HIV-infected Women

Conditions
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HIV Infection

Intervention / Treatment
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* Drug: 1 Transdermal Testosterone (Patch)
* Drug: 2 Placebo Patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female 18 - 55 BMI less than or equal to 26 HIV-infected Androgen deficient, with free testosterone < 3 pg/mL Stable antiretroviral regimen for 3 months prior to study Tubal ligation, hysterectomy, or verbalized understanding of appropriate barrier contraception methods. Subjects will be counseled in appropriate barrier contraception methods and the counseling will be documented. Exclusion Criteria: Use of anabolic agent, including testosterone, GH or other preparations within 3 months of the study. Use of megestrol acetate within 3 months of the study Use of estrogen or any preparation known to affect bone density or bone turnover.This includes oral contraceptives, depo provera or combined progesterone-estrogen injections, and transdermal contraceptive patches. Pregnant or breast-feeding Hgb < 9.0 mg/dL Current participation in another research study conducted by this investigator or past participation in the DHEA study funded by the same grant as this protocol. Creatinine > 1.5 mg/dL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Transdermal Testosterone (Patch)<br>300 micrograms applied twice a week | Drug: 1 Transdermal Testosterone (Patch)<br>* 300 micrograms twice a week<br>|
| Placebo Comparator: 2 Placebo Patch (identical in appearance)<br>placebo patch (0 micrograms of testosterone)applied twice a week | Drug: 2 Placebo Patch<br>* Placebo patch (0 micrograms of testosterone) applied twice a week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lean Body Mass | Represents change in measure from baseline to 18 months. 18 month mean and standard error of the mean for lean body mass measured by dual energy absorptiometry (DEXA)scan. | Baseline (time 0) to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Mineral Density of the Hip | Represents change in measure from baseline to 18 months. 18 month mean and standard error of the mean for bone mineral density of the hip measured by dual energy absorptiometry (DEXA)scan. | Baseline (time 0) to 18 months | 
| Quality of Life/Depression: Becks Depression Inventory | Represents change in the mean score from baseline to 18 months. Depression was evaluated with the Beck's Depression Inventory (BDI). The BDI is a 21-item self-report instrument used to assess the presence and severity of symptoms of depression. A Total score in the range of 0-13 is considered minimal, 14-19 is mild, 20-28 is moderate, and 29-63 is severe. | Baseline (time 0) to 18 months | 
| Quality of Life/Sexual Function: Brief Index of Sexual Function (BISF-W) Domain 7: Problems Affecting Sexual Function | Represents change in measure from baseline to 18 months. The BISF is 22 items with seven domains: Thoughts and Desires, Arousal, Frequency of Sexual Activity, Receptivity/Initiation, Pleasure, Relationship Satisfaction, and Problems Affecting Sexual Function. Data from Domain 7: Problems Affecting Sexual Function is reported. The score range for this domain is -16 to 75,a higher score indicates greater sexual function. | Baseline (time 0) to 18 months | 
| Safety: Number of Subjects Reporting a Skin Reaction to the Patch | Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant. | Baseline (time 0) to 18 months | 
| Safety: Number of Subjects Reporting a Change in Hair Pattern (Increased Hair on Chin, Upper Lip, Chest, Abdomen, Fore Arms, and Legs) | Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant. | Baseline (time 0) to 18 months | 
| Safety: Number of Subjects Reporting Acne | Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant. | Baseline (time 0) to 18 months | 
| Safety: Number of Subjects Reporting a Change in Menstrual Status (Reported More Than One Period in 1 Month or Missed a Period During a Monthly Cycle) | Represents number of subjects who reported this symptom from baseline to 18 months. Every 6 weeks,subjects were counseled on appropriate barrier contraception methods and a urine pregnancy was performed. Subjects who experienced increased hair growth (facial hair) could remain in the study on a lower dose of testosterone (1 patch per week), but dose reductions were not necessary and full dosing was continued throughout the study for all subjects. Changes in menstrual status, missed periods and/or irregular bleeding, were noted and reported back to the primary care physician if significant. | Baseline (time 0) to 18 months | 
| Neurocognitive Function: Hopkins Verbal Learning Test-revised,Total Recall Z Score Represents Change in Z Score From Baseline to 18 Months. | This test assesses verbal learning and memory. Subjects are given a list of 12 words and asked to repeat as many words as they can recall during 3 separate trials. The Total Recall Z score is calculated based on the sum of total correct responses for Trials 1,2,& 3. A Z score of 0 equals the 50 percentile, a Z score of 1 is 1 standard deviation above the mean and a Z score of -1 is 1 standard deviation below the mean. The lowest and highest T scores for the HVLT-R are ≤20 and ≥80. This correlates to lowest and highest Z scores of ≤ -3.0 and ≥3.0. A lower Z score is indicative of poor recall. | Baseline (time 0) to 18 months | 
| Strength: Total Knee Flexion Performed Via Quantitative Muscle Function Testing. | Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds. | Baseline (time 0) to 18 months | 
| Strength: Total Knee Extension Performed Via Quantitative Muscle Function Testing. | Represents change in isometric force (measured in kilograms) from baseline to 18 months. Peak isometric force of total knee flexion and extension were measured on the best of 2 repetitions for which subjects held a maximum contraction for 5 seconds. | Baseline (time 0) to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, women, androgen, Treatment Experienced