Menopausal HT for Women Living With HIV (HoT)

Phase 4

Not yet recruiting

• Conditions: HIV Infection; Menopause
• Interventions: Drug: Transdermal estradiol gel; Drug: Placebo for estradiol gel; Drug: Micronized Progesterone; Drug: Placebo for micronized progesterone

• Registration Number: NCT06856174
• Lead Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-02-19
• Study First Submitted QC: 2025-02-28
• Study First Posted: 2025-03-04
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-11
• Last Update Posted: 2025-07-14
• Study Start: 2026-01-19
• Primary Completion: 2027-09-20
• Study Completion: 2027-09-20

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 105

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A: Hormone Therapy	Transdermal estradiol gel	PARTICIPANTS WITH INTACT UTERUS: Transdermal estradiol gel plus oral micronized progesterone daily for 12 weeks. PARTICIPANTS WITHOUT A UTERUS: Transdermal estradiol gel daily for 12 weeks.
Arm A: Hormone Therapy	Micronized Progesterone	PARTICIPANTS WITH INTACT UTERUS: Transdermal estradiol gel plus oral micronized progesterone daily for 12 weeks. PARTICIPANTS WITHOUT A UTERUS: Transdermal estradiol gel daily for 12 weeks.
Arm B: Hormone Therapy Placebo	Placebo for estradiol gel	PARTICIPANTS WITH INTACT UTERUS: Transdermal placebo gel plus oral encapsulated placebo pill daily for 12 weeks. PARTICIPANTS WITHOUT A UTERUS: Transdermal placebo gel alone daily for 12 weeks.
Arm B: Hormone Therapy Placebo	Placebo for micronized progesterone	PARTICIPANTS WITH INTACT UTERUS: Transdermal placebo gel plus oral encapsulated placebo pill daily for 12 weeks. PARTICIPANTS WITHOUT A UTERUS: Transdermal placebo gel alone daily for 12 weeks.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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.
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 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.
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