Development of Pregnenolone as a Treatment for Depression

NCT ID: NCT03645096

Last Updated: 2024-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-01
• Study Completion Date: 2022-05-31

Brief Summary

Pregnenolone, an over-the-counter supplement, is a naturally occurring neurosteroid made in the adrenal glands and brain. Preclinical research suggests pregnenolone has antidepressant, cognitive enhancing, and neuroprotective properties, particularly in women. The following hypothesis will be tested in this trial: pregnenolone is associated with improvement in depressive symptom severity in women that is associated with changes in the resting state functional connectivity (rsFC) and GABA.

Detailed Description

In this study, 26 adult women meeting criteria for Major Depressive Disorder (MDD) as defined in DSM 5, will be randomized to a double-blind, placebo-controlled, crossover phase I clinical trial of pregnenolone (i.e. each participant receives 500 mg/d, 800 mg/d pregnenolone and placebo in random order). The study will consist of three 7-day treatment exposures to each pregnenolone dose with a 14-day washout between each exposure. Baseline evaluation will include medical and psychiatric history, psychiatric interview, standard laboratory analyses (i.e., blood draw, ECG), and a brief cognitive battery. Neuroimaging will be collected after each study drug or placebo administration. Study drug tolerability and participant safety will be assessed throughout the study (6 in-clinic visits + a safety visit) using structured clinical interviews, self-report questionnaires, and standard laboratory analyses.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Pregnenolone 500 > Pregnenolone 800 > Placebo

3 exposures in order:

1. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.

2. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.

3. Matching placebo capsule by mouth, daily for 7 days.

Group Type: EXPERIMENTAL

Pregnenolone 500 mg

Intervention Type: DRUG

Pregnenolone 500 mg capsule.

Pregnenolone 800 mg

Intervention Type: DRUG

Pregnenolone 800 mg capsule.

Placebo

Intervention Type: DRUG

Placebo capsule manufactured to mimic pregnenolone capsule.

Pregnenolone 500 > Placebo > Pregnenolone 800

3 exposures in order:

1. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.

2. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.

3. Pregnenolone 800 mg capsule by mouth, daily for 7 days.

Group Type: EXPERIMENTAL

Pregnenolone 500 mg

Intervention Type: DRUG

Pregnenolone 500 mg capsule.

Pregnenolone 800 mg

Intervention Type: DRUG

Pregnenolone 800 mg capsule.

Placebo

Intervention Type: DRUG

Placebo capsule manufactured to mimic pregnenolone capsule.

Pregnenolone 800 > Pregnenolone 500 > Placebo

3 exposures in order:

1. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.

2. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.

3. Matching placebo capsule by mouth, daily for 7 days.

Group Type: EXPERIMENTAL

Pregnenolone 500 mg

Intervention Type: DRUG

Pregnenolone 500 mg capsule.

Pregnenolone 800 mg

Intervention Type: DRUG

Pregnenolone 800 mg capsule.

Placebo

Intervention Type: DRUG

Placebo capsule manufactured to mimic pregnenolone capsule.

Pregnenolone 800 > Placebo > Pregnenolone 500

3 exposures in order:

1. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.

2. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.

3. Pregnenolone 500 mg capsule by mouth, daily for 7 days.

Group Type: EXPERIMENTAL

Pregnenolone 500 mg

Intervention Type: DRUG

Pregnenolone 500 mg capsule.

Pregnenolone 800 mg

Intervention Type: DRUG

Pregnenolone 800 mg capsule.

Placebo

Intervention Type: DRUG

Placebo capsule manufactured to mimic pregnenolone capsule.

Placebo > Pregnenolone 500 > Pregnenolone 800

3 exposures in order:

1. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.

2. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout.

3. Pregnenolone 800 mg capsule by mouth, daily for 7 days.

Group Type: EXPERIMENTAL

Pregnenolone 500 mg

Intervention Type: DRUG

Pregnenolone 500 mg capsule.

Pregnenolone 800 mg

Intervention Type: DRUG

Pregnenolone 800 mg capsule.

Placebo

Intervention Type: DRUG

Placebo capsule manufactured to mimic pregnenolone capsule.

Placebo > Pregnenolone 800 > Pregnenolone 500

3 exposures in order:

1. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout.

2. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout.

3. Pregnenolone 500 mg capsule by mouth, daily for 7 days.

Group Type: EXPERIMENTAL

Pregnenolone 500 mg

Intervention Type: DRUG

Pregnenolone 500 mg capsule.

Pregnenolone 800 mg

Intervention Type: DRUG

Pregnenolone 800 mg capsule.

Placebo

Intervention Type: DRUG

Placebo capsule manufactured to mimic pregnenolone capsule.

Interventions

Pregnenolone 500 mg

Pregnenolone 500 mg capsule.

Intervention Type: DRUG

Pregnenolone 800 mg

Pregnenolone 800 mg capsule.

Intervention Type: DRUG

Placebo

Placebo capsule manufactured to mimic pregnenolone capsule.

Intervention Type: DRUG

Other Intervention Names

Neurosteroid; Neurosteroid

Eligibility Criteria

Inclusion Criteria

• Women, ages 18-65 years, with current MDD (mild or moderate severity per DSM-5) based on SCID-CV.
• No psychotropic medications, other than PRN (as needed) hypnotics, within 28 days of randomization (medication free).
• PRN hypnotics allowed up to 3 days prior to study drug administrations but not while receiving study drug.

Exclusion Criteria

• Severe MDD based on DSM-5 severity criteria and/or a baseline HRSD score > 27 (consistent with severe depressive symptom severity).
• High risk for suicide (active SI with plan/intent or > 2 lifetime attempts in lifetime or any in the past 6 months).
• Treatment resistant depression (fail two adequate antidepressant trials or ECT during current episode).
• Vulnerable populations (e.g. pregnant/nursing, severe cognitive or intellectual impairment, incarcerated).
• Coronary artery disease, atrial fibrillation, stroke, deep vein thrombosis, pulmonary embolism or blood clotting disorder, or any severe, life threatening or unstable, medical condition.
• History of allergic reaction or side effects with prior pregnenolone use.
• Current substance use disorder defined as meeting criteria for a use disorder based on the SCID interview and self-reported use within the past 3 months, or a positive baseline urine drug screen.
• Current psychotic features (hallucinations, delusions, disorganized thought processes) or eating disorders.
• Anxiety disorders of sufficient severity to be the primary focus of clinical attention (e.g. severe obsessive compulsive or post-traumatic stress disorders).
• Hormone-sensitive conditions (i.e. breast cancer; uterine/ovarian cancer, endometriosis, uterine fibroids).
• Clinically significant laboratory, physical examination, or electrocardiogram (ECG) findings.
• Currently using oral contraceptives containing progestin (barrier methods allowed).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Sherwood Brown, MD, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sherwood Brown, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R61AT009625-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU 052018-030

Identifier Type: -

Identifier Source: org_study_id