Clinical trial NCT03645096: Development of Pregnenolone as a Treatment for Depression
Official title: NCCIH Development of Pregnenolone as a Treatment for Depression R61 Phase
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Major Depressive Disorder
Keywords: Depression
Pregnenolone
Women
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2018-08-24
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Adult women with mild to moderate major depressive disorder (MDD) will receive pregnenolone (500 mg/d, 800 mg/d and placebo) in a randomized, double-blind, crossover design.
Primary purpose: BASIC_SCIENCE

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.

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).

Primary outcomes:
measure: Amygdala-PCC Functional Connectivity
timeFrame: 7 days
measure: dlPFC-Insula Functional Connectivity
timeFrame: 7 days
measure: GABA Concentration.
timeFrame: 7 days
Secondary outcomes:
measure: Pregnenolone Level
timeFrame: 7 days
measure: Allopregnanolone Level
timeFrame: 7 days
measure: Systematic Assessment for Treatment Emergent Events (SAFTEE)
timeFrame: 7 days
measure: Pregnenolone Dose
timeFrame: 7 days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Sherwood Brown, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: