- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03645096
Development of Pregnenolone as a Treatment for Depression R61
August 29, 2022 updated by: Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center
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
Completed
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
29
Phase
- 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
-
-
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
Ages Eligible for Study
16 years to 63 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
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 |
Intervention / Treatment |
---|---|
Experimental: Pregnenolone 500 > Pregnenolone 800 > Placebo
3 exposures in order:
|
Pregnenolone 500 mg capsule.
Pregnenolone 800 mg capsule.
Placebo capsule manufactured to mimic pregnenolone capsule.
|
Experimental: Pregnenolone 500 > Placebo > Pregnenolone 800
3 exposures in order:
|
Pregnenolone 500 mg capsule.
Pregnenolone 800 mg capsule.
Placebo capsule manufactured to mimic pregnenolone capsule.
|
Experimental: Pregnenolone 800 > Pregnenolone 500 > Placebo
3 exposures in order:
|
Pregnenolone 500 mg capsule.
Pregnenolone 800 mg capsule.
Placebo capsule manufactured to mimic pregnenolone capsule.
|
Experimental: Pregnenolone 800 > Placebo > Pregnenolone 500
3 exposures in order:
|
Pregnenolone 500 mg capsule.
Pregnenolone 800 mg capsule.
Placebo capsule manufactured to mimic pregnenolone capsule.
|
Experimental: Placebo > Pregnenolone 500 > Pregnenolone 800
3 exposures in order:
|
Pregnenolone 500 mg capsule.
Pregnenolone 800 mg capsule.
Placebo capsule manufactured to mimic pregnenolone capsule.
|
Experimental: Placebo > Pregnenolone 800 > Pregnenolone 500
3 exposures in order:
|
Pregnenolone 500 mg capsule.
Pregnenolone 800 mg capsule.
Placebo capsule manufactured to mimic pregnenolone capsule.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional connectivity.
Time Frame: 7 days
|
Amygdala-PCC or dlPFC-insula functional connectivity using structural neuroimaging.
|
7 days
|
GABA concentration.
Time Frame: 7 days
|
Occipital GABA concentration using spectroscopy.
|
7 days
|
Systematic Assessment for Treatment Emergent Events (SAFTEE).
Time Frame: 7 days
|
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).
The higher total score (all items summed together) indicates a higher level of side effect burden.
|
7 days
|
Serum pregnenolone level.
Time Frame: 7 days
|
Measure blood serum pregnenolone and allopregnanolone levels.
|
7 days
|
Pregnenolone dose.
Time Frame: 7 days
|
Identify a dose of pregnenolone that demonstrates bioavailabilit and tolerability.
|
7 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- 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)
September 1, 2019
Primary Completion (Actual)
May 31, 2022
Study Completion (Actual)
May 31, 2022
Study Registration Dates
First Submitted
August 22, 2018
First Submitted That Met QC Criteria
August 22, 2018
First Posted (Actual)
August 24, 2018
Study Record Updates
Last Update Posted (Actual)
August 31, 2022
Last Update Submitted That Met QC Criteria
August 29, 2022
Last Verified
August 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STU 052018-030
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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