HIV Infection, Menopause
Conditions
Brief summary
Women living with HIV have been shown to experience more frequent and severe hot flashes and night sweats (collectively known as vasomotor symptoms) as compared to women living without HIV. This correlates with disturbed sleep, increased depressive symptoms, increased anxiety, worse mental function, interference with activities of daily living including work, and worse overall quality of life. Hormone therapy is considered to be the most effective therapy for hot flashes and night sweats and the most appropriate choice to prevent bone loss at the time of menopause for women without HIV. However, the usefulness of hormone therapy has not been specifically studied in women living with HIV. This trial is being done to see if: * There is evidence to support the use of hormone therapy (estradiol with or without progesterone) for the treatment of hot flashes and night sweats in women living with HIV * Hormone therapy improves mental function, mood, sleep, quality of life, bone health, heart health, and inflammation in women living with HIV * Hormone therapy is safe and tolerable for women living with HIV
Interventions
All participants: Estradiol gel 0.1%, 0.75 grams (corresponding to estradiol 0.75 mg) applied to the skin of the upper thigh once daily for 12 weeks.
DRUGMicronized Progesterone
Participants with intact uterus: Encapsulated micronized progesterone 100 mg orally once daily for 12 weeks.
All participants: Placebo for estradiol gel 0.1%, 0.75 grams applied to the skin of the upper thigh once daily for 12 weeks.
DRUGPlacebo for micronized progesterone
• Participants with intact uterus: Encapsulated placebo for micronized progesterone 100 mg orally once daily for 12 weeks.
Sponsors
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute on Aging (NIA)
Exeltis
Xiromed LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Living with HIV * Assigned female sex at birth * Between the ages of 40 and 60 years * In the late menopausal transition (perimenopause) or early postmenopause * Experiencing hot flashes and/or night sweats * Willing and able to complete a daily diary * Does not have medical condition that would contraindicate hormone therapy * Not taking medications to treat hot flashes * Not taking medications that cannot be combined with hormone therapy * Receiving antiretrovirals (HIV medication) for more than 1 year * Not pregnant and willing and able to use at least non-hormonal birth control to prevent pregnancy * Willing and able to provide informed consent after discussion with the research staff
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in vasomotor symptoms (VMS) frequency | From 5 weeks prior to randomization to Week 12 | Change in self-reported mean VMS frequency per day from 5-week observation phase prior to randomization to the one-week period prior to week 12 visit following. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in vasomotor symptom (VMS) severity | From 5 weeks prior to randomization to week 12 | Change in self-reported mean severity of VMS from 5-week observation phase prior to randomization to the one-week period prior to week 12 visit following randomization; severity scale is ordinal: none (0), mild (1), moderate (2), severe (3). |
| Change in sleep | From randomization to week 12 | Change in total sleep scores from randomization visit to week 12 visit as measured by the Pittsburgh Sleep Quality Index (PSQI). Total sleep score determined by summing responses from seven assessments, where each assessment is scored from 0 (best) to 3 (worst). The minimum possible total sleep score is 0 (best) and the maximum possible score is 21 (worst). Higher total scores suggest more severe sleep problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes. |
| Change in insomnia | From randomization to week 12 | Change in total insomnia scores from randomization visit to week 12 visit as measured by the Insomnia Severity Index (ISI). Total insomnia score determined by summing responses from seven assessments, each rated on a Likert 5-point scale, where 0 indicates no problems and 4 indicates severe problems. The minimum possible total insomnia score is 0 (best) and the maximum possible score is 28 (worst). Higher total scores suggest more severe insomnia problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes. |
| Change in quality of life | From randomization to week 12 | Change in total health-related quality of life score, from randomization visit to week 12 visit as measured by Menopause specific Quality of life questionnaire (MenQOL). Total health-related quality of life score is determined by averaging responses from four domain-specific scores (vasomotor \[3 items\], physical \[16 items\], psychosocial \[7 items\], sexual functioning \[3 items\], each ranging from 1 (best) to 8 (worst)). Domain-specific scores represent the average score among the items in a domain. The score for each item, ranging from 1 (best) to 8 (worst), represents the sum of the presence of the symptom (1 for no, 2 for yes) and the severity, rated on a Likert 7-point scale (0, not bothered at all to 6, extremely bothered), The minimum possible quality of life score is 1 (best) and the maximum possible score is 8 (worst). Higher scores suggest more severe quality of life problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes. |
| Percentage of participants with adverse events associated with hormone therapy | From randomization to week 12 | Adverse events (AE) associated with study treatment with severity grade of 3 or higher as per DAIDS Toxicity grading scale. |
| Percentage of participants with occurrence of abnormal vaginal bleeding | From randomization to week 12 | Abnormal vaginal bleeding adverse event defined as any of the following: any report of heavy bleeding, 2 or more episodes of spotting or greater at intervals of \< 21 days among participants in late menopausal transition, any occurrence after 6 weeks of hormone treatment among post-menopausal participants. |
| Percentage of participants with intolerance of hormone therapy | From randomization to week 12 | Intolerance of hormone therapy is defined as permanent discontinuation prior to the week 12 visit that was not required per protocol nor recommended due to safety considerations. |
| Change in neurocognitive test results | From randomization to week 12 | Change in neurocognition as measured by the neuropsychological (NP) battery from randomization visit to week 12 visit. |
| Change in depression symptoms | From randomization to week 12 | Change in depression symptoms score from randomization visit to week 12 visit as measured by Patient Health Questionnaire-9 (PHQ-9). Total depression score determined by summing responses from nine assessments, where each assessment is scored from 0 (not at all) to 3 (nearly every day). The minimum possible total sleep score is 0 (best) and the maximum possible score is 27 (worst). Higher total scores suggest more severe depression problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes. |
| Change in anxiety symptoms | From randomization to week 12 | Change in anxiety symptoms score from randomization visit to week 12 as measured by Generalized Anxiety Disorder 7-item (GAD-7). Total anxiety score determined by summing responses from seven Likert assessments, where each assessment is scored from 0 (best) to 3 (worst). The minimum possible total anxiety score is 0 (best) and the maximum possible score is 21 (worst). Higher total scores suggest more severe anxiety problems. Change in total score calculated as Week 12 minus baseline. Negative change indicates better outcomes. |
| Change in weight | From randomization to week 12 | Absolute and Percent change in total body weight from randomization visit to week 12 visit. |
| Change in body mass index (BMI) | From randomization to week 12 | Absolute change in BMI from randomization visit to week 12 visit |
| Change in waist circumference | From randomization to week 12 | Absolute change in minimum waist circumference from randomization visit to week 12 visit |
| Change in waist-to-hip ratio | From randomization to week 12 | Change in waist-to-hip circumference ratio between the randomization visit and the week 12 visit |
| Change in sexual function | From randomization to week 12 | Change in total sexual function score from randomization visit to week 12 visit as measured by the female sexual function index (FSFI). Total sexual function score is determined by summing six domain-specific scores (desire \[2 items\], arousal \[4 items\], lubrication \[4 items\], orgasm \[3 items\], satisfaction \[3 items\], and pain \[3 items\]), ranging from 0 (worst) to 6 (best). Domain-specific scores represent the sum of the scores for each item within a domain (ranging from 0 (worst) to 6 (best)), multiplied by a factor to adjust for relative weighting (0.6 for desire; 0.3 for arousal; 0.3 for lubrication; 0.4 for orgasm; 0.4 for satisfaction; and 0.4 for pain). The minimum possible sexual function score is 2 (worst) and the maximum possible score is 36 (best). Lower scores indicate worse sexual function. Change in total score calculated as Week 12 minus baseline. Positive change indicates better outcomes. |
| Percentage of participants with female sexual distress | Week 12 visit | Female sexual distress defined as, at the week 12 visit, endorsing frequently or always to question regarding how often distressed or bothered about sex life in the past 4 weeks. |
Countries
United States
Contacts
CONTACTACTG ClinicalTrials.gov Coordinator
Outcome results
None listed