Pregnenolone for Menopausal Depression

Overseen By Emine Akar, BS

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: University of Texas Southwestern Medical Center

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

HYPOTHESIS: Pregnenolone administration will be associated with greater reduction in depressive symptom severity than placebo in women with current mMDD. STUDY AIMS: Primary Aim: Determine if pregnenolone is associated with greater reduction in depressive symptom severity than placebo in women with mMDD, as measured by MADRS. Secondary Aims: 1. Determine if pregnenolone is associated with greater reduction in anxiety symptom severity than placebo in women with mMDD. 2. Determine if pregnenolone is associated with greater improvement in cognition than placebo in women with mMDD. 3. Determine if pregnenolone is associated with greater improvement in quality of life than placebo in women with mMDD. 4. Determine if pregnenolone is associated with greater improvement in vasomotor symptoms of menopause than placebo. Mechanistic Aims: 1. Determine whether changes in neurosteroid levels with pregnenolone mediate clinical response. 2. Determine if baseline neurosteroid levels predict pregnenolone response. 3. Determine whether depressive symptoms, anxiety, sleep or vasomotor symptoms improve first. A crossed-lagged panel model will explore serial correlations between changes in outcome measures.

Research Team

Sherwood Brown, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Marlene Freeman, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

Women aged 40-62 experiencing menopause or early postmenopausal symptoms, with significant hot flashes and diagnosed major depressive disorder. They must not be using certain medications or supplements for menopause and depression, have uncontrolled health conditions, or a history of hormone-sensitive tumors.

Inclusion Criteria

I use a hormonal IUD and my FSH level is over 20.

Women meeting DSM-5 criteria for current major depressive disorder

I experience severe symptoms due to menopause.

Exclusion Criteria

My family or I have a history of hormone-sensitive tumors.

My depression has not improved with treatment.

Pregnancy, intending pregnancy or breast feeding

Treatment Details

Interventions

• Pregnenolone (Neurosteroid)

Trial Overview The trial is testing if Pregnenolone can better reduce depression in perimenopausal women compared to a placebo. It also looks at effects on anxiety, cognition, quality of life, and vasomotor symptoms. The study measures changes in neurosteroid levels to understand the treatment's mechanism.

Participant Groups

Group I: Pregnenlone (phase 1 and 2) Experimental Treatment 1 Intervention

Participants will receive pregnenolone at phase 1 (baseline-WK 7) and 2 (WK 8-16). The titration schedule is as follows: at baseline a 50 mg (BID, 7 days). WK 1=150 mg (BID, 7 days); WK 2=250 mg (BID, 14 days) and WK 4=250 mg (BID, 14 days) (BID, 14 days). At phase 2 (WK 8) to maintain the double blind of rerandomization, treatment in all conditions recommence at a dosage frequency similar to phase 1. At WK 8=250 mg (BID, 7 days); at WK 9=250 mg (BID, 7 days); WK 10=250 mg (BID, 14 days) and WK 12=250 mg (BID, 14 days) . During the participants' final WK (16), they will be instructed to titrate down the treatment according to the following schedule: 150 mg (BID, 4 days) and 50 mg (BID, 4 days), discontinue.

Group II: Placebo rerandom to pregnenolone Experimental Treatment 2 Interventions

Participants will receive placebo at phase 1 (baseline-WK 7) \& treatment response assessed (MADRS score reduced \<50% at WK8). Nonresponders are rerandomized to receive either treatment at phase 2 (WK8-16).The titration schedule is as follows (dosage throughout is BID): at baseline placebo (7 days). At WK 1=placebo (7 days); WK 2=placebo (14 days) \& WK 4=placebo (14 days). Placebo nonresponders who are rerandomized to pregnenolone: At WK 8=250 mg (7 days);WK 9=250 mg (7 days);WK 10=250 mg (14 days) \& WK 12=250 mg (14 days). During the participants' final WK (16), they will be instructed to titrate down the treatment according to the following schedule: 150 mg (4 days) and 50 mg (4 days), discontinue.

Group III: Placebo rerandom to placebo Placebo Group 1 Intervention

Participants will receive placebo at phase 1 (baseline-WK 7) \& treatment response assessed (MADRS score reduced \<50% at WK8). Nonresponders are rerandomized to receive either treatment at phase 2 (WK8-16).The titration schedule is as follows (dosage throughout is BID): at baseline placebo (7 days). At WK 1= placebo (7 days); at WK 2=placebo (14 days) and WK 4=placebo (14 days). Placebo nonresponders rerandomized to placebo: At WK 8=placebo (7 days);WK 9=placebo (7 days);WK 10=placebo (14 days) and WK 12=placebo (14 days). During the participants' final WK (16), they will be instructed to titrate down (done in order to maintain the double blind) the treatment according to the following schedule: placebo (4 days) and placebo (4 days), discontinue.

Group IV: Placebo responsive cont placebo Placebo Group 1 Intervention

Participants will placebo throughout phase 1 (baseline- WK 7) \& treatment response assessed (MADRS score reduced \<50% at WK8). Responders continue to receive placebo at phase 2 (WK8-16).The titration schedule is as follows (dosage throughout is BID): at baseline placebo (7 days). At WK 1=placebo (7 days); WK 2=placebo (14 days) \& WK 4=placebo (14 days). Placebo responders remain on placebo: At WK 8, placebo (7 days); WK 9=placebo (7 days); WK 10=placebo (14 days) \& WK 12=placebo (14 days). During the participants' final WK (16), they will be instructed to titrate down (done in order to maintain the double blind) the treatment according to the following schedule: placebo= 4 days) and placebo=4 days, discontinue.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+