Using methylphenidate to treat PTSD and cognitive issues in veterans

Randomized Placebo-Controlled Trial of Methylphenidate for the Treatment of Post-Traumatic Stress Disorder With Associated Neurocognitive Complaints

This study is testing whether a medication called methylphenidate can help veterans with PTSD and thinking problems feel better.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: VA Office of Research and Development (fed)
• Locations: 3 sites (Birmingham, Alabama and 2 other locations)
• Trial ID: NCT05776056 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of methylphenidate, a stimulant medication, in treating posttraumatic stress disorder (PTSD) and associated neurocognitive complaints in veterans. The innovative N-of-1 design allows each participant to alternate between receiving methylphenidate and a placebo every 4-5 weeks over a 20-week period, ensuring a robust comparison of treatment effects. The study aims to assess changes in PTSD symptoms and cognitive functioning through this randomized, double-blind approach. Results from this trial could provide valuable insights into new treatment options for veterans struggling with PTSD.

Who should consider this trial

Good fit: Ideal candidates for this study are veterans aged 18 to 65 who have a diagnosis of PTSD and experience subjective neurocognitive impairment.

Not a fit: Patients with severe psychotic disorders or substance use disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve cognitive functioning and reduce PTSD symptoms in veterans.

How similar studies have performed: Previous studies have shown promising results for methylphenidate in improving cognitive functioning in related conditions, suggesting potential for success in this novel application.

Eligibility criteria

Inclusion Criteria:

1. Any gender Veteran of the US military between the ages of 18 and 65 years
2. Independent decision-making capacity to sign informed consent and HIPAA (i.e., no surrogate consent)
3. Diagnosis of PTSD defined by DSM-5 symptom count on CAPS-5
4. CAPS-5 past month total score greater than or equal to 26
5. Subjective neurocognitive impairment, defined as a total score of greater than or equal to 25 (1 standard deviation below the mean) on the NeuroQoL Cognitive Function 8-item self-report form.

Exclusion Criteria:

1. Diagnosis of DSM-5-defined bipolar I, schizophrenia spectrum or other psychotic disorders (by MINI)
2. Presence of severe psychotic symptoms such that, based on the clinical judgement of the investigator or treatment provider, treatment with an antipsychotic is required.
3. Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 2 months. Patients who utilize alcohol or cannabis but do not meet criteria for moderate or severe disorder are permitted at the discretion of the investigator. Participants must agree to abstain from illicit drugs, including cannabis products containing THC even when legal by state law.
4. History of severe TBI as defined by the Ohio State University TBI Identification Method.
5. Diagnosis of dementia or related progressive neurocognitive disorder, based on clinical records.
6. Increased risk of suicide that necessitates inpatient treatment or treatment excluded by the protocol; and/or intensity of suicidal ideation (Type 4 or Type 5) or any suicidal behavior in the past 2 months on Columbia Suicide Severity Rating Scale (C-SSRS).
7. Pregnancy or lactation, or anticipated pregnancy at any point during study participation. Participants of child-bearing potential must have negative pregnancy test at study entry and must agree to adhere to a medically acceptable method of birth control (e.g., oral, implantable, injectable, or transdermal hormone-based contraceptives; intrauterine device; double-barrier method).
8. Use of any investigational drug, MPH formulation, antipsychotics, mood stabilizers, monoamine oxidase inhibitors, stimulants, atomoxetine, or bupropion within 2 weeks of baseline.
9. Treatment with evidence-based trauma-focused therapy for PTSD within 2 weeks of baseline (if participant is receiving therapy, he/she must complete treatment prior to entering study). Supportive psychotherapy may be continued during the study.
10. A clinically significant acute or uncontrolled chronic medical/surgical illness that would contraindicate use of MPH, or a known terminal illness.
11. Prior allergic reaction to any MPH formulation.
12. Litigating for compensation for a psychiatric disorder outside the Veterans benefits compensation and pension process.
13. Current enrollment in another interventional trial for PTSD.

Where this trial is running

Birmingham, Alabama and 2 other locations

• Birmingham VA Medical Center, Birmingham, AL — Birmingham, Alabama, United States (RECRUITING)
• Tuscaloosa VA Medical Center, Tuscaloosa, AL — Tuscaloosa, Alabama, United States (RECRUITING)
• VA Puget Sound Health Care System Seattle Division, Seattle, WA — Seattle, Washington, United States (RECRUITING)

Study contacts

• Principal investigator: Rebecca C. Hendrickson, MD PhD — VA Puget Sound Health Care System Seattle Division, Seattle, WA
• Study coordinator: Rebecca C Hendrickson, MD PhD

Conditions: Posttraumatic Stress Disorder, PTSD, ADHD, Neurocognitive, Stimulant, Veteran, Traumatic Brain Injury, TBI