Pregnenolone for Menopausal Depression

Overseen By Emine Akar, BS

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: SERMs, Hormone therapy, Hormonal contraceptives, others

Disqualifiers: Pregnancy, Bipolar, Substance use, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether pregnenolone, a natural hormone, can reduce depression symptoms in women undergoing menopause. Researchers also seek to determine its effects on anxiety, memory, quality of life, and menopause symptoms like hot flashes. Women experiencing depression along with noticeable menopause symptoms, such as frequent hot flashes, may be suitable candidates for this trial. Participants will receive either pregnenolone or a placebo to compare the effects. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works and measuring its effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop certain medications. The trial excludes the use of hormone replacement therapy, hormonal contraceptives (except certain IUDs), and some natural supplements. Antidepressants are allowed if you've been on a stable dose for at least 4 weeks.

Is there any evidence suggesting that pregnenolone is likely to be safe for humans?

Research has shown that pregnenolone, a natural substance in the body, serves as the starting point for making steroid hormones. It is usually well-tolerated as a supplement. Some studies have examined its effects on brain health and found it may aid thinking and memory. However, its overall effects remain not fully understood.

Regarding side effects, some individuals might experience mild issues like headaches or an upset stomach. Since this treatment is still under investigation, detailed safety information is limited. Early trials primarily focus on assessing the treatment's safety for people. Researchers continue to learn about pregnenolone's effects and monitor for any negative reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pregnenolone is unique because it offers a new approach to treating menopausal depression by utilizing a naturally occurring steroid hormone. Unlike standard antidepressants or hormone replacement therapies, pregnenolone targets neurosteroid pathways, which may offer mood stabilization and cognitive benefits. Researchers are excited about its potential to provide relief with fewer side effects, making it an appealing alternative for those who struggle with the side effects of traditional treatments. Additionally, pregnenolone's ability to work on different brain pathways might result in a faster onset of action compared to conventional options.

What evidence suggests that pregnenolone might be an effective treatment for menopausal depression?

Research has shown that pregnenolone, which participants in this trial may receive, might help reduce depression symptoms in women going through menopause. It likely works by affecting certain brain chemicals that influence mood. Early findings suggest pregnenolone could be more effective than a placebo in lessening depression. It may also help with anxiety, improve thinking skills, and enhance overall quality of life. While more research is needed, these initial results are promising for those experiencing menopausal depression. ^{6 7 8 9 10}

Who Is on the Research Team?

Sherwood Brown, MD, PhD

Principal Investigator

UT Southwestern Medical Center

Marlene Freeman, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive pregnenolone or placebo from baseline to week 7 with titration schedule

7 weeks

Weekly visits for dosage adjustment and monitoring

Treatment Phase 2

Participants continue with pregnenolone or placebo from week 8 to week 16 with titration schedule

8 weeks

Weekly visits for dosage adjustment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pregnenolone

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.

How Is the Trial Designed?

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+

Citations

1. womensmentalhealth.org womensmentalhealth.org/posts/new-research-study-at-the-cwmh-a-novel-treatment-for-menopausal-depression/

New Research Study at the CWMH: A Novel Treatment ... ... pregnenolone may be a promising treatment for depression. Dr. Freeman's study will test the effectiveness of pregnenolone in women with menopausal depression.

2. mghpsychnews.org mghpsychnews.org/new-study-will-investigate-novel-antidepressant-for-the-treatment-of-menopausal-depression/

New Study Will Investigate Novel Antidepressant for the ... Dr. Freeman's study will test the effectiveness of pregnenolone in women with menopausal depression. You can learn more about the study HERE.

3. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/a_neurosteroid_inter

A Neurosteroid Intervention for Menopausal and ... The proposed clinical trial seeks to demonstrate the efficacy of pregnenolone as an antidepressant among women in the menopausal transition and to examine the ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03505905/a-neurosteroid-intervention-for-menopausal-and-perimenopausal-depression

A Neurosteroid Intervention for Menopausal and ... HYPOTHESIS: Pregnenolone administration will be associated with greater reduction in depressive symptom severity than placebo in women with current mMDD.

5. womensmentalhealth.org womensmentalhealth.org/posts/pregnenolone-menopause-study-2-2/

Pregnenolone Neurosteroid for Menopausal Depression Dr. Freeman's study will test the effectiveness of pregnenolone in women with menopausal depression.

6. en.wikipedia.org en.wikipedia.org/wiki/Pregnenolone

Pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-98/pregnenolone

Pregnenolone - Uses, Side Effects, and More Pregnenolone is a chemical that comes from cholesterol. It's used to make steroid hormones in the body. It can also be made in a lab and used as medicine.

8. amazon.com amazon.com/Pregnenolone-Tested-Capsules-Serving-Supplements/dp/B0713R1T2T

Pregnenolone 100mg per Serving (Converted to ... SUPPORTS COGNITIVE FUNCTION: Pregnenolone supports myelination and aids in the formation of new synapses which may support brain health and cognitive ...

9. shop.bioticsresearch.com shop.bioticsresearch.com/products/pregnenolone-25

Pregnenolone 25 Pregnenolone is a steroid hormone from cholesterol, converted to other hormones, and a neurosteroid impacting synaptic function and neuroprotective.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4057431/

Pregnenolone Can Protect the Brain from Cannabis ... Pregnenolone is considered the inactive precursor of all steroid hormones and its potential functional effects have been largely neglected.