A Phase 2 Evaluation of Potential Pharmacotherapeutic Interventions in Active-Duty Service Members and Veterans With PTSD

• Status: Not yet recruiting
• Trial end date: 2026-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 2 randomized, double-blinded, placebo-controlled study that will evaluate multiple potential pharmacotherapeutic interventions for PTSD utilizing an adaptive platform trial design. Subjects are randomized among the multiple cohorts in the study and the resulting randomization enables sharing/pooling of control subjects, where all interventions may be compared to a common control (placebo). This master protocol describes the default procedures and analyses for all cohorts; treatment-specific procedures will be described in the platform cohort appendices and individual cohorts may have additional eligibility requirements or safety and efficacy procedures.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: U.S. Army Medical Research and Development Command
• Collaborator: PPD
• Treatments: Fluoxetine; Vilazodone Hydrochloride

Criteria

Inclusion Criteria: A subject must meet all the following criteria to be eligible to participate in this study:

1. Provides written informed consent and HIPAA authorization.

2. Is male or female, ≥18 and <65 years of age at screening.

3. Meets DSM-5 criteria for PTSD according to CAPS-5-R, Past Month assessment.

4. Is at least 3 months post the index trauma at screening.

5. Has a CAPS-5-R, Past Month total score of ≥26 at Screening. If the Baseline visit is >30 days after Screening, the CAPS-5-R assessment will be repeated at the Baseline visit to verify continued eligibility.

Note: The CAPS-5 scoring grid will be used to score answers and to calculate the total score to determine eligibility.

6. Is currently serving, or has previously served, in a branch of the US military service (eg, Air Force, Army, Navy, Marine Corps, and Coast Guard including Reserves and National Guard).

7. Agrees to consistently use an acceptable method of birth control as defined in Section 7.4.2 (required for both males and females who are of reproductive potential and sexually active with partners of the opposite sex) throughout the duration of subjects' active involvement in the study and for at least 30 days after the last dose of study treatment or as specified in the assigned cohort appendix (Table 3).

1. For females of reproductive potential, acceptable birth control methods are defined as: hormonal contraceptives, intrauterine device, or double barrier contraception (ie, condom + diaphragm, condom or diaphragm + spermicidal gel or foam). Hormonal contraceptives must have been started at least 2 months prior to the Baseline visit. In addition, agrees to no egg donation or in vitro fertilization procedures for the duration of the study and for at least 30 days after the last dose of study treatment or as specified in the assigned cohort appendix (Table 3).

2. Non-reproductive potential for females is defined by a post-menopausal or surgically sterile status. Post-menopause is defined as 1 year without menses; if in question, a FSH of >40 U/mL, per central laboratory testing must be documented. Surgical sterility (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) must be documented.

3. Females of reproductive potential must have a negative pregnancy test at the screening (serum) and baseline (urine) visits.

4. For males, adequate birth control methods will be defined as the use of double barrier contraception (eg, condom + diaphragm, condom or diaphragm + spermicidal gel or foam). In addition, male subjects must agree not to donate sperm for the duration of the study and for at least 30 days after the last dose of study treatment or as specified in the assigned cohort appendix (Table 3).

5. Non-reproductive potential for males is defined as surgical sterility (ie, vasectomy) at least 3 months prior to screening.

8. Is able and willing to participate in study assessments and undergo blood draws.

9. Is willing to undergo MRI eg, is not claustrophobic, and has no contraindications to MRI.

10. Is fluent in English, both spoken and written.

Exclusion Criteria: A subject who meets any of the following criteria will not be eligible to participate in this trial:

1. Is pregnant or breastfeeding at the Screening or Baseline visits, or desires pregnancy during the study.

2. Is at risk for suicide based on any of the following:

1. Had any suicidal ideation or behavior (including preparatory behavior) that required psychiatric hospitalization for stabilization in the 3 months prior to screening.

2. Had more than 2 actual suicide attempts within the last 3 years, not including interrupted or aborted attempts, preparatory acts or behaviors, or non-suicidal self injurious behavior (as per C SSRS response).

3. Has any history of an acute exacerbation of suicidal ideation and/or intent and/or a suicide-related psychiatric hospitalization following initiation of a medication (eg, SSRI).

3. Is taking any prohibited medication per Section 8.5.1 or cohort-specific appendix restrictions (Table 3) or is unable/unwilling to discontinue medications. Subjects must agree to a washout period of at least 2 weeks or 5 half-lives, whichever is longer, prior to the first dose of study treatment.

4. In the 3 months prior to Baseline, has initiated or terminated individual or group PTSD specific psychotherapy (eg, Eye Movement Desensitization & Reprocessing, Prolonged Exposure, Cognitive Processing Therapy, Stress Inoculation Training, Present Centered Therapy), or therapy is anticipated to conclude during the study. Completion of ≤2 sessions in the prior 3 months with no plans to continue is not exclusionary. Subjects in stable trauma-focused or non-trauma focused therapy must agree to continue treatment for the duration of participation in the study.

5. Has undergone or plans to undergo gender reassignment surgery. Note: subjects who are currently undergoing stable hormone replacement therapy are eligible for inclusion in the study.

6. Meets DSM-5 (American Psychiatric Association 2013) criteria for moderate (≥4 symptoms) or severe (≥6 symptoms) AUD or other SUDs, including cannabis, hallucinogens, inhalants, opioids, sedatives, hypnotics, anxiolytics, or stimulants within 3 months of screening. Nicotine use disorder is allowed.

7. Has a positive screen for illicit drug use (not including cannabis) or recent heavy alcohol consumption (as indicated by GGT outside of normal range) at Screening and the Baseline visits.

8. Has lifetime history or current diagnosis of any psychosis, such as bipolar I disorder, schizophrenia, schizoaffective disorder, depression with psychotic features, or other psychotic disorders (except for delirium). Hallucinations consistent with re-experiencing symptoms are not exclusionary.

9. Has a current diagnosis of OSA considered not well-managed (AHI >5) with C-, Bi-, or V PAP. Subjects who have AHI >5 at Screening with the WatchPAT One may re-screen prior to Baseline or provide a note from their physician stating that their CPAP machine readings are <5.

10. Has a history of neoplastic disease in the last 5 years, except for basal cell carcinoma or non-metastatic squamous cell carcinoma of the skin that been adequately treated.

11. Has any clinically significant abnormal findings on the 12-lead ECG at the Screening or Baseline visits, as determined by the central rater.

12. Has clinically significant abnormal laboratory results at the Screening visit that indicate inadequate renal function:

1. serum creatinine >1.5 mg/dL OR

2. estimated creatinine clearance of <50 mL/min calculated by the Cockcroft and Gault formula).

13. Has clinically significant abnormal laboratory results at the Screening visit that indicate impaired liver function:

1. ALT or AST >2 × ULN and/or

2. total bilirubin level >1.5 × ULN

3. prolonged PT >1.2 × ULN

4. subjects previously diagnosed with Gilbert's syndrome are allowed.

14. Has a prior history of drug induced liver injury characterized by ALT or AST >3 × ULN AND total bilirubin level >2 × ULN without cholestasis (ie, Alkaline Phosphatase <2 × ULN); this is generally referred to as Hy's Law.

15. Has any other abnormal laboratory result at the Screening visit that could impact the subject's safety or participation in the study, as determined by the Site PI.

16. Has any other concurrent psychiatric or medical condition that would impact the subject's safety, ability to appropriately complete evaluations, or participation in the study, as determined by the Site PI.

17. Does not have a permanent address and will not have a stable method of contact (eg, no cell phone) over the duration of the study.

18. Is currently involved in litigation, medical evaluation for disability benefits or damages, or benefit examination related to the PTSD diagnosis.

19. Has participated in any interventional clinical trial or treatment with any investigational drug or other investigational intervention within 3 months or 5 half-lives, whichever is longer, of screening.

Note: previous participation in an observational study is permitted. Note: Subjects who are enrolled in this APT, and who are eligible for re randomization, are permitted to remain in the study and receive alternative cohort intervention following a 2-week or 5 half-lives washout period, whichever is longer.

20. Is unavailable for the duration of the trial, unlikely to be compliant with the protocol, or deemed by the Site PI to be unsuitable for participation in the trial for any reason.