NCCIH Development of Pregnenolone as a Treatment for Depression R61 Phase
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Amygdala-PCC Functional Connectivity
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: Pregnenolone 500 mg (Drug)
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.
干预措施: Pregnenolone 800 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Pregnenolone 500 mg (Drug)
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.
干预措施: Pregnenolone 800 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Pregnenolone 500 mg (Drug)
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.
干预措施: Pregnenolone 800 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Pregnenolone 500 mg (Drug)
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.
干预措施: Pregnenolone 800 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Pregnenolone 500 mg (Drug)
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.
干预措施: Pregnenolone 800 mg (Drug)
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.
干预措施: Placebo (Drug)
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.
干预措施: Pregnenolone 500 mg (Drug)
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.
干预措施: Pregnenolone 800 mg (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Amygdala-PCC Functional Connectivity
时间窗: 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).
dlPFC-Insula Functional Connectivity
时间窗: 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).
GABA Concentration.
时间窗: 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.
次要结局
- Pregnenolone Level(7 days)
- Allopregnanolone Level(7 days)
- Systematic Assessment for Treatment Emergent Events (SAFTEE)(7 days)
- Pregnenolone Dose(7 days)
研究者
Sherwood Brown, MD, PhD
Professor
University of Texas Southwestern Medical Center