Development of Pregnenolone as a Treatment for Depression R61

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ClinicalTrials.gov Identifier: NCT03645096

Recruitment Status : Recruiting

First Posted : August 24, 2018

Last Update Posted : January 26, 2021

See Contacts and Locations

Sponsor:

Collaborator:

National Center for Complementary and Integrative Health (NCCIH)

Information provided by (Responsible Party):

Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Pregnenolone 500 mg Drug: Pregnenolone 800 mg Drug: Placebo	Phase 1

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	26 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Basic Science
Official Title:	Development of Pregnenolone as a Treatment for Depression R61
Actual Study Start Date :	September 1, 2019
Estimated Primary Completion Date :	May 31, 2021
Estimated Study Completion Date :	May 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Depression

Drug Information available for: Pregnenolone

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pregnenolone 500 > Pregnenolone 800 > Placebo 3 exposures in order: Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout. Matching placebo capsule by mouth, daily for 7 days.	Drug: Pregnenolone 500 mg Pregnenolone 500 mg capsule. Drug: Pregnenolone 800 mg Pregnenolone 800 mg capsule. Drug: Placebo Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: Pregnenolone 500 > Placebo > Pregnenolone 800 3 exposures in order: Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 800 mg capsule by mouth, daily for 7 days.	Drug: Pregnenolone 500 mg Pregnenolone 500 mg capsule. Drug: Pregnenolone 800 mg Pregnenolone 800 mg capsule. Drug: Placebo Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: Pregnenolone 800 > Pregnenolone 500 > Placebo 3 exposures in order: Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout. Matching placebo capsule by mouth, daily for 7 days.	Drug: Pregnenolone 500 mg Pregnenolone 500 mg capsule. Drug: Pregnenolone 800 mg Pregnenolone 800 mg capsule. Drug: Placebo Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: Pregnenolone 800 > Placebo > Pregnenolone 500 3 exposures in order: Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout. Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 500 mg capsule by mouth, daily for 7 days.	Drug: Pregnenolone 500 mg Pregnenolone 500 mg capsule. Drug: Pregnenolone 800 mg Pregnenolone 800 mg capsule. Drug: Placebo Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: Placebo > Pregnenolone 500 > Pregnenolone 800 3 exposures in order: Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 500 mg capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 800 mg capsule by mouth, daily for 7 days.	Drug: Pregnenolone 500 mg Pregnenolone 500 mg capsule. Drug: Pregnenolone 800 mg Pregnenolone 800 mg capsule. Drug: Placebo Placebo capsule manufactured to mimic pregnenolone capsule.
Experimental: Placebo > Pregnenolone 800 > Pregnenolone 500 3 exposures in order: Matching placebo capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 800 mg capsule by mouth, daily for 7 days followed by 14 day washout. Pregnenolone 500 mg capsule by mouth, daily for 7 days.	Drug: Pregnenolone 500 mg Pregnenolone 500 mg capsule. Drug: Pregnenolone 800 mg Pregnenolone 800 mg capsule. Drug: Placebo Placebo capsule manufactured to mimic pregnenolone capsule.

Outcome Measures

Primary Outcome Measures :

Functional connectivity. [ Time Frame: 7 days ]
Amygdala-PCC or dlPFC-insula functional connectivity using structural neuroimaging.
GABA concentration. [ Time Frame: 7 days ]
Occipital GABA concentration using spectroscopy.
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.
Serum pregnenolone level. [ Time Frame: 7 days ]
Measure blood serum pregnenolone and allopregnanolone levels.
Pregnenolone dose. [ Time Frame: 7 days ]
Identify a dose of pregnenolone that demonstrates bioavailabilit and tolerability.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03645096

Contacts

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Contact: Alexandra Kulikova, MS	2146456967	alexandra.kulikova@utsouthwestern.edu
Contact: Sherwood Brown, MD, PhD	2146456950	sherwood.brown@utsouthwestern.edu

Locations

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United States, Texas
UT Southwestern Medical Center	Recruiting
Dallas, Texas, United States, 75390
Contact: Alexandra Kulikova, MS
Contact 2146456967 alexandra.kulikova@utsouthwestern.edu
Principal Investigator: Sherwood Brown, MD, PhD

Sponsors and Collaborators

University of Texas Southwestern Medical Center

National Center for Complementary and Integrative Health (NCCIH)

Investigators

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Principal Investigator:	Sherwood Brown, MD, PhD	UT Southwestern Medical Center

More Information

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Responsible Party:	Sherwood Brown, MD, PhD, Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT03645096
Other Study ID Numbers:	STU 052018-030
First Posted:	August 24, 2018 Key Record Dates
Last Update Posted:	January 26, 2021
Last Verified:	January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Sherwood Brown, MD, PhD, University of Texas Southwestern Medical Center:


Depression Pregnenolone Women

Additional relevant MeSH terms:

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Depression Depressive Disorder Depressive Disorder, Major	Behavioral Symptoms Mood Disorders Mental Disorders

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