Pregnenolone to improve function in Veterans with anxiety and depression
A New Intervention to Improve Function in Veterans With Anxiety and Depression
This trial will test whether pregnenolone can help Veterans with anxiety and depression reduce symptoms and improve sleep, pain, and daily functioning.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 84 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | VA Office of Research and Development Federal |
| Locations | 1 site (Durham, North Carolina) |
| Trial ID | NCT06188923 on ClinicalTrials.gov |
What this trial studies
Veterans receiving care at the Durham VAHCS with moderate-or-worse anxiety and depression (PHQ-ADS ≥20) will be enrolled to receive oral pregnenolone or placebo while symptoms and function are tracked. Outcome measures include psychiatric symptoms, functional impairment, sleep quality, and pain over the treatment period. Key exclusions include high PTSD symptom scores (PCL-5 ≥38), active suicidal or homicidal ideation requiring intervention, allergy to pregnenolone, and medical conditions that would make pregnenolone unsafe. The trial tests a neurosteroid precursor strategy aimed at restoring allopregnanolone-related signaling to relieve multiple co-occurring symptoms.
Who should consider this trial
Good fit: Veterans enrolled for care at the Durham VAHCS with moderate or greater anxiety and depression symptoms (PHQ-ADS ≥20), who meet safety criteria and agree to required non-hormonal contraception if applicable, are ideal candidates.
Not a fit: Patients with primary PTSD (PCL-5 ≥38), active suicidal or homicidal ideation requiring clinical intervention, contraindicating medical conditions, or those using hormonal contraceptives may not be eligible or likely to benefit.
Why it matters
Potential benefit: If successful, pregnenolone could offer a single, well-tolerated medication to reduce anxiety and depression symptoms while also improving sleep, pain, and daily functioning for Veterans.
How similar studies have performed: Preclinical data and prior clinical work, including a randomized trial showing pregnenolone reduced low back pain in Veterans, support its potential, but larger confirmatory trials for combined anxiety, depression, sleep, and pain outcomes are limited.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Veterans enrolled for care at the Durham VAHCS * Veterans who score a minimum score of 20 or higher (moderate symptoms) on the PHQ-ADS (Kroenke et al 2017) * Oral pregnenolone could reduce the effectiveness of oral contraceptives, thus women 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 PREG * Medical disorders that may preclude safe administration of PREG or exacerbate mental or physical health symptoms * PTSD diagnosis, as per the PCL-5, scores of 38 or higher * Current suicidal or homicidal ideation necessitating clinical intervention or representing an imminent concern * Prior attempts 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) * Standard pharmacological interventions for mental health disorders will not be exclusionary; however, there may be no changes in psychotropic medications for mental or physical health conditions 4 weeks prior to study randomization * Benzodiazepine or opioid 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 * Due to lack of safety data in pregnant and breast-feeding women, female participants who are pregnant or breast-feeding will be excluded * As indicated by the DSM-5, moderate or severe Substance Use Disorders (excluding caffeine and tobacco) within 1 month of study entry
Where this trial is running
Durham, North Carolina
- Durham VA Medical Center, Durham, NC — Durham, North Carolina, United States (Recruiting)
Study contacts
- Principal investigator: Jennifer C Naylor, PhD — Durham VA Medical Center, Durham, NC
- Study coordinator: Jennifer C Naylor, PhD
- Email: jennifer.naylor2@va.gov
- Phone: (919) 286-0411
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.