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Development of Pregnenolone as a Treatment for Depression R61

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Pregnenolone 500 mg
Pregnenolone 800 mg
Placebo
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Major Depressive Disorder focused on measuring Depression, Pregnenolone, Women

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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).

Sites / Locations

  • UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Pregnenolone 500 > Pregnenolone 800 > Placebo

Pregnenolone 500 > Placebo > Pregnenolone 800

Pregnenolone 800 > Pregnenolone 500 > Placebo

Pregnenolone 800 > Placebo > Pregnenolone 500

Placebo > Pregnenolone 500 > Pregnenolone 800

Placebo > Pregnenolone 800 > Pregnenolone 500

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Functional connectivity.
Amygdala-PCC or dlPFC-insula functional connectivity using structural neuroimaging.
GABA concentration.
Occipital GABA concentration using spectroscopy.
Systematic Assessment for Treatment Emergent Events (SAFTEE).
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.
Measure blood serum pregnenolone and allopregnanolone levels.
Pregnenolone dose.
Identify a dose of pregnenolone that demonstrates bioavailabilit and tolerability.

Secondary Outcome Measures

Full Information

First Posted
August 22, 2018
Last Updated
August 29, 2022
Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Center for Complementary and Integrative Health (NCCIH)
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1. Study Identification

Unique Protocol Identification Number
NCT03645096
Brief Title
Development of Pregnenolone as a Treatment for Depression R61
Official Title
Development of Pregnenolone as a Treatment for Depression R61
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 1, 2019 (Actual)
Primary Completion Date
May 31, 2022 (Actual)
Study Completion Date
May 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
National Center for Complementary and Integrative Health (NCCIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
Depression, Pregnenolone, Women

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pregnenolone 500 > Pregnenolone 800 > Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Pregnenolone 500 > Placebo > Pregnenolone 800
Arm Type
Experimental
Arm Description
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.
Arm Title
Pregnenolone 800 > Pregnenolone 500 > Placebo
Arm Type
Experimental
Arm Description
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.
Arm Title
Pregnenolone 800 > Placebo > Pregnenolone 500
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo > Pregnenolone 500 > Pregnenolone 800
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo > Pregnenolone 800 > Pregnenolone 500
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Pregnenolone 500 mg
Intervention Description
Pregnenolone 500 mg capsule.
Intervention Type
Drug
Intervention Name(s)
Pregnenolone 800 mg
Intervention Description
Pregnenolone 800 mg capsule.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsule manufactured to mimic pregnenolone capsule.
Primary Outcome Measure Information:
Title
Functional connectivity.
Description
Amygdala-PCC or dlPFC-insula functional connectivity using structural neuroimaging.
Time Frame
7 days
Title
GABA concentration.
Description
Occipital GABA concentration using spectroscopy.
Time Frame
7 days
Title
Systematic Assessment for Treatment Emergent Events (SAFTEE).
Description
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.
Time Frame
7 days
Title
Serum pregnenolone level.
Description
Measure blood serum pregnenolone and allopregnanolone levels.
Time Frame
7 days
Title
Pregnenolone dose.
Description
Identify a dose of pregnenolone that demonstrates bioavailabilit and tolerability.
Time Frame
7 days

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sherwood Brown, MD, PhD
Organizational Affiliation
UT Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Development of Pregnenolone as a Treatment for Depression R61

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