Methylphenidate for the Treatment of PTSD With Associated Neurocognitive Complaints

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

Methylphenidate for the Treatment of PTSD With Associated Neurocognitive Complaints (NCT05776056) is a Phase 4 interventional studying Posttraumatic Stress Disorder (PTSD), sponsored by VA Office of Research and Development. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

Posttraumatic stress disorder (PTSD) is frequently accompanied by difficulty concentrating, poor memory, and inability to keep up with tasks, which negatively impacts a person's ability to function at work and in relationships. Currently available treatments do not fully relieve all symptoms. A published research report showed positive evidence that the stimulant medication methylphenidate was beneficial in treating these problems. This study will evaluate the ability of methylphenidate to treat PTSD and associated neurocognitive complaints in Veterans. An innovative feature is the study's N-of-1 design. In this design, every participant will move back and forth every 4-5 weeks between treatment with methylphenidate and treatment with placebo, in random order and under double-blind conditions, over a 20-week period. The investigators will compare the aggregated change in PTSD and neurocognitive symptoms between periods of treatment with methylphenidate versus placebo. Results will help clinicians to better choose the best treatment for Veterans living with PTSD.

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 70 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Posttraumatic Stress Disorder (PTSD) subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Any gender Veteran of the US military between the ages of 18 and 65 years 2. Independent decision-making capacity to sign willing to sign a consent form 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. Who Should NOT Join This Trial: 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). ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

DRUG

Methylphenidate

Methylphenidate 10mg will be taken twice daily.

DRUG

Placebo

An inactive pill (placebo) will be taken twice daily.

Locations (3)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, United States

Tuscaloosa VA Medical Center, Tuscaloosa, AL

Tuscaloosa, Alabama, United States

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05776056), the sponsor (VA Office of Research and Development), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05776056 clinical trial studying?

Who can participate in NCT05776056?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05776056?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05776056. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05776056. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.