Neurosteroids for PTSD in Veterans
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|ClinicalTrials.gov Identifier: NCT03799562|
Recruitment Status : Recruiting
First Posted : January 10, 2019
Last Update Posted : May 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|Posttraumatic Stress Disorder||Drug: Pregnenolone Drug: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Participants will be randomized to receive the active study medication (pregnenolone) or placebo.|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||This is a randomized, double-blind, placebo-controlled trial. All roles will be masked with the exception of the research pharmacist.|
|Official Title:||Neurosteroid Intervention for PTSD in Iraq/Afghanistan-era Veterans|
|Actual Study Start Date :||May 1, 2019|
|Estimated Primary Completion Date :||December 1, 2024|
|Estimated Study Completion Date :||December 1, 2024|
Placebo lead in 14 DAYS, followed by Pregnenolone 50 mg BID x 14 DAYS, followed by Pregnenolone 150 mg BID x 14 DAYS, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial
Pregnenolone 50 mg BID x 14 DAYS, followed by Pregnenolone 150 mg BID x 14 DAYS, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial. Placebo will be identical to the pregnenolone arm, except placebo will be dispensed.
Placebo Comparator: Placebo
Same as pregnenolone (active study medication), except placebo dispensed.
Same as pregnenolone (active study medication), except placebo dispensed.
- Change in Clinician Administered PTSD Scale for DSM-5 (Visit 6-Baseline) [ Time Frame: Through study completion, an average of 5 years ]The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to make a diagnosis of PTSD and assess PTSD symptoms. It assesses the intensity and frequency of PTSD symptoms. Scores range from 0-80; higher score indicates greater severity.
- Change in Brief Pain Inventory, Short Form (Visit 6-Baseline) [ Time Frame: Through study completion, an average of 5 years ]The Brief Pain Inventory, Short Form (BPI-SF) is a self-reported scale that measures the severity of pain and the interference of pain on function. The scores range from 0 (no pain) to 10 (pain as severe as you can imagine). There are 4 questions assessing worst pain, least pain, average pain in the past 24 hours, and the pain right now. The Interference scores range from 0 (does not interfere) to 10 (completely interferes). There are 7 questions assessing the interference of pain in the past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life.
- Change in Hamilton-Depression Inventory (Visit 6-Baseline) [ Time Frame: Through study completion, an average of 5 years ]The HAM-D measures the severity of depressive symptoms. It is a checklist of 17 items that are ranked on a scale of 0-4 or 0-2. The range for the total score (which is the sum of the scores of all 17 items) is 0-52; a higher score indicates greater severity of symptoms.
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): NCT03799562
|Contact: Jennifer C Naylor, PhD||(919) 286-0411 ext email@example.com|
|Contact: Christine E Marx, MD MA||(919) 286-0411 ext firstname.lastname@example.org|
|United States, North Carolina|
|Durham VA Medical Center, Durham, NC||Recruiting|
|Durham, North Carolina, United States, 27705|
|Contact: Bradley J Olson 919-286-6926 Bradley.Olson@va.gov|
|Contact: John D Whited, MD MHS (919) 286-0411 ext 6926 email@example.com|
|Principal Investigator: Jennifer C Naylor, PhD|
|Principal Investigator:||Jennifer C Naylor, PhD||Durham VA Medical Center, Durham, NC|