Development of Pregnenolone as a Treatment for Depression

April 25, 2024 updated by: Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center

NCCIH Development of Pregnenolone as a Treatment for Depression R61 Phase

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
34

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: Pregnenolone 500 mg
Pregnenolone 500 mg capsule.
Other Names:
  • Neurosteroid
Drug: Pregnenolone 800 mg
Pregnenolone 800 mg capsule.
Other Names:
  • Neurosteroid
Drug: Placebo
Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: 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.
Drug: Pregnenolone 500 mg
Pregnenolone 500 mg capsule.
Other Names:
  • Neurosteroid
Drug: Pregnenolone 800 mg
Pregnenolone 800 mg capsule.
Other Names:
  • Neurosteroid
Drug: Placebo
Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: 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.
Drug: Pregnenolone 500 mg
Pregnenolone 500 mg capsule.
Other Names:
  • Neurosteroid
Drug: Pregnenolone 800 mg
Pregnenolone 800 mg capsule.
Other Names:
  • Neurosteroid
Drug: Placebo
Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: 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.
Drug: Pregnenolone 500 mg
Pregnenolone 500 mg capsule.
Other Names:
  • Neurosteroid
Drug: Pregnenolone 800 mg
Pregnenolone 800 mg capsule.
Other Names:
  • Neurosteroid
Drug: Placebo
Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: 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.
Drug: Pregnenolone 500 mg
Pregnenolone 500 mg capsule.
Other Names:
  • Neurosteroid
Drug: Pregnenolone 800 mg
Pregnenolone 800 mg capsule.
Other Names:
  • Neurosteroid
Drug: Placebo
Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: 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.
Drug: Pregnenolone 500 mg
Pregnenolone 500 mg capsule.
Other Names:
  • Neurosteroid
Drug: Pregnenolone 800 mg
Pregnenolone 800 mg capsule.
Other Names:
  • Neurosteroid
Drug: Placebo
Placebo capsule manufactured to mimic pregnenolone capsule.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Amygdala-PCC Functional Connectivity
Time Frame: 7 days

Determine if an increase in Amygdala-PCC functional connectivity is observed with pregnenolone as compared to placebo.

Amygdala-PCC functional connectivity was measured using resting state fMRI blood-oxygen-level dependent (BOLD) response and transformed to standardized z-scores (with μ=0 and σ=1) for analysis. Functional connectivity was measured three times corresponding to three treatments (500 mg pregnenolone, 800 mg pregnenolone, and placebo). Better outcomes are represented by greater functional connectivity, and are indicated by a higher z-score at 500 mg or 800 mg, relative to that at placebo (i.e., there is no absolute threshold).
7 days
dlPFC-Insula Functional Connectivity
Time Frame: 7 days

Determine if an increase in dlPFC-Insula functional connectivity is observed with pregnenolone as compared to placebo.

dlPFC-Insula functional connectivity was measured using resting state fMRI blood-oxygen-level dependent (BOLD) response and transformed to standardized z-scores (with μ=0 and σ=1) for analysis. Functional connectivity was measured three times corresponding to three treatments (500 mg pregnenolone, 800 mg pregnenolone, and placebo). Better outcomes are represented by greater functional connectivity, and are indicated by a higher z-score at 500 mg or 800 mg, relative to that at placebo (i.e., there is no absolute threshold).
7 days
GABA Concentration.
Time Frame: 7 days

Determine if an increase in occipital GABA concentration is observed with pregnenolone, as compared to placebo.

Occipital GABA concentration using spectroscopy with tCr reference. Higher concentration values are representative of a greater anti-depressant effect.
7 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pregnenolone Level
Time Frame: 7 days
Assess bioavailability of pregnenolone by demonstrating increases in serum pregnenolone and allopregnanolone with pregnenolone administration. Change (increases) in blood serum pregnenolone levels are indicative of bioavailability.
7 days
Allopregnanolone Level
Time Frame: 7 days
Assess bioavailability of pregnenolone by demonstrating increases in serum pregnenolone and allopregnanolone with pregnenolone administration. Change (increases) in blood serum allopregnanolone levels are indicative of bioavailability.
7 days
Systematic Assessment for Treatment Emergent Events (SAFTEE)
Time Frame: 7 days

Assess safety and tolerability of pregnenolone at the doses tested.

SAFTEE is a side effect self-report assessment scale that consists of 56 potential side effects. Participants rate how bothersome each side effect is on a scale of "none" (0), "mild" (1), "moderate" (2), "severe" (3). Total scores range from 0 to 168. A higher total score (sum of all items) indicates a higher level of side effect burden.
7 days
Pregnenolone Dose
Time Frame: 7 days
Identify a dose of pregnenolone that demonstrates bioavailability (see "Pregnenolone Level" and "Allopregnanolone Level" outcome measures), tolerability (see "SAFTEE" outcome measure); and is associated with a significant change in a biosignature.
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Texas Southwestern Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Center for Complementary and Integrative Health (NCCIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sherwood Brown, MD, PhD, UT Southwestern Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 22, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 22, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 24, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 1, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STU 052018-030
  • 1R61AT009625-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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