Neurosteroids for PTSD in Veterans

  • STATUS
    Recruiting
  • End date
    Dec 1, 2024
  • participants needed
    90
  • sponsor
    VA Office of Research and Development
Updated on 29 January 2021

Summary

This study seeks to determine if pregnenolone can improve symptoms of PTSD and other symptoms that commonly occur with PTSD in Iraq/Afghanistan-era Veterans. The total study duration is 10 weeks. Eligible Veterans with PTSD will receive either pregnenolone or placebo throughout the study duration and will complete mental and physical health assessments at each study visit. Eligible participants will attend 6 in-person study visits and receive several short "check-in" phone calls.

Description

BACKGROUND: There is an acute and urgent need to develop new and effective posttraumatic stress disorder (PTSD) pharmacotherapies, as there are currently only two FDA-approved medications for the treatment of PTSD (both of which are from the same drug class and have shown only moderate effect sizes in FDA registration trials). Many Veterans with PTSD thus remain symptomatic despite the availability of these treatments, increasing the likelihood of receiving pharmacological treatment interventions for which there is little or no empirical evidence. Multiple national and VA working groups focusing on PTSD have identified the critical need to address the paucity of PTSD pharmacotherapies, and have strongly recommended more randomized clinical trials to evaluate possible effective pharmacological treatments. Both preclinical and clinical data suggest that reductions in neurosteroids are involved in the pathophysiology of PTSD, and that ameliorating these deficits could potentially be clinically therapeutic - the proposed investigation targeting a neurosteroid intervention for the treatment of PTSD could thus be a promising research avenue. The investigators therefore propose to conduct a randomized clinical trial (RCT) to determine the efficacy of a neurosteroid intervention (pregnenolone) for PTSD and commonly co-occurring disorders in Iraq/Afghanistan-era Veterans, an understudied cohort that may be less treatment-refractory.

METHODS: This study will be a 10-week randomized, placebo-controlled, double-blind clinical trial of pregnenolone or matching placebo in Veterans with PTSD. The trial will include a 2-week single-blind placebo lead-in phase followed by 8 weeks of study medication (placebo or pregnenolone). Forty-five subjects meeting DSM-5 criteria for PTSD (as measured by a CAPS-5 score of 30) will be randomized to receive pregnenolone, and 45 subjects meeting DSM-5 criteria for PTSD will be randomized to receive placebo. The primary outcome for this RCT will be changes in total CAPS-5 score at Visit 6 for this modified intent-to-treat sample. Secondary clinical outcomes for this RCT include changes in pain intensity and functional interference, as measured by the Brief Pain Inventory, Short Form (BPI-SF) and depression symptoms by the Hamilton-Depression Rating Scale (HAM-D). Blood samples will be collected for serum analysis at all study visits and frozen in a -80 degree freezer. Upon completion of the study, samples will be thawed and analyzed using Gas Chromatography/Mass Spectrometry for neurosteroid analyses and inflammatory markers will be quantified. Genetic analyses will be conducted to determine therapeutic response.

PREDICTED RESULTS: The investigators hypothesize that treatment with pregnenolone will be efficacious in Iraq/Afghanistan-era Veterans with PTSD, and will significantly reduce PTSD symptoms as assessed by the CAPS-5 (primary endpoint) compared to placebo. Secondary endpoints will include the assessment of conditions that frequently co-occur with PTSD; specifically, the investigators hypothesize that pregnenolone will also demonstrate efficacy for co-occurring chronic pain symptoms and depression symptoms. The investigators hypothesize that increases in pregnenolone and other neurosteroids (and decreases in inflammatory markers) will predict improvements in PTSD, depression, and chronic pain symptoms. The investigators also hypothesize that neurosteroids are dysregulated in PTSD, and that specific SNPs of genes coding for neurosteroidogenic enzymes will be associated with therapeutic response.

Details
Condition Post-Traumatic Stress Disorder, Post-Traumatic Stress Disorders, PTSD
Treatment Placebo, Pregnenolone
Clinical Study IdentifierNCT03799562
SponsorVA Office of Research and Development
Last Modified on29 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 65 yrs?
Gender: Male or Female
Do you have any of these conditions: Post-Traumatic Stress Disorders or Post-Traumatic Stress Disorder?
Do you have any of these conditions: Post-Traumatic Stress Disorders or Post-Traumatic Stress Disorder or PTSD?
DSM-5 diagnosis of PTSD with CAPS-5 Total Score 3
Females will be required to use a medically and study approved contraceptive or otherwise not be of child-bearing potential
Birth control methods must be non-hormonal
No anticipated need to alter psychiatric medications for duration of study involvement
Ability to participate fully in the informed consent process

Exclusion Criteria

History of allergy to pregnenolone
Medical disorders that may preclude safe administration of pregnenolone or exacerbate PTSD symptoms
Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern
Prior suicide attempt history or suicidal ideation that does not require clinical intervention or represent an imminent concern is permitted
Serious unstable medical illness, such as
history of cerebrovascular accident
prostate
uterine or breast cancer
others (at the discretion of the PI and medical oversight team)
Medical conditions not well controlled will be excluded, at the discretion of the PI and Medical Team
Standard pharmacological interventions for PTSD will not be exclusionary, including, but not limited to
antidepressant medications such as SSRIs, SNRIs, tricyclics, bupropion, mirtazapine, venlafaxine, and nefazodone
mood stabilizers such as carbamazepine, divalproex, lamotrigine, topiramate
atypical antipsychotics, and other agents including prazosin
However, there may be no changes in psychotropic medications for PTSD 4 weeks prior to study randomization
Benzodiazepine use
Current diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition other than mild TBI (assessed at screening)
Initiation or change in psychotherapy within 3 months of randomization
i.e., psychotherapy must be stable for 3 months prior to study start
Participants on hormonal therapies such as finasteride or hormonal birth control
Female participants who are pregnant or breast-feeding
As indicated by the DSM-5, moderate or severe Substance Use Disorders (excluding caffeine and tobacco) within 1 month of study entry
Mild Alcohol Use Disorder is not exclusionary, at the judgment of the PI and her medical team
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