Methylphenidate for the Treatment of PTSD With Associated Neurocognitive Complaints

NCT05776056 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: MHBP-006-22SCX002546
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Posttraumatic Stress Disorder (PTSD)

Keywords

PTSD; Posttraumatic Stress Disorder; ADHD; Neurocognitive; Stimulant; Veteran; Traumatic Brain Injury; TBI; Methylphenidate

Outcome Measures

Primary Outcomes (1)

• PTSD Symptom Checklist for DSM-5 (PCL-5)

  PTSD Checklist for DSM-5 (PCL-5) is a 20-item self-report that assesses how much the participant was bothered by each DSM-5 symptoms of PTSD with a rating of 0 "not at all" to 4 "extremely;" summed score ranges from 0-80 with higher score indicating more severe symptoms.

  4 weeks

Secondary Outcomes (2)

• Neuro-QoL Cognitive Function short form (NeuroQoL)

  4 weeks

• Symbol Digit Coding (SDC)

  4 weeks

Study Arms (2)

N-of-1 crossover study enrollment: start with placebo

OTHER

All participants spend time receiving both active study drug (methylphenidate) and placebo (sham study drug), in randomized order, across 4 treatment blocks separated by 1 week washout periods (where no study drug is given).

Drug: Methylphenidate; Drug: Placebo

N-of-1 crossover study enrollment: start with methylphenidate

OTHER

All participants spend time receiving both active study drug (methylphenidate) and placebo (sham study drug), in randomized order, across 4 treatment blocks separated by 1 week washout periods (where no study drug is given).

Drug: Methylphenidate; Drug: Placebo

Interventions

Placebo DRUG

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

N-of-1 crossover study enrollment: start with methylphenidate; N-of-1 crossover study enrollment: start with placebo

Methylphenidate DRUG

Methylphenidate 10mg will be taken twice daily.

Also known as: Ritalin

N-of-1 crossover study enrollment: start with methylphenidate; N-of-1 crossover study enrollment: start with placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any gender Veteran of the US military between the ages of 18 and 65 years
• Independent decision-making capacity to sign informed consent and HIPAA (i.e., no surrogate consent)
• Diagnosis of PTSD defined by DSM-5 symptom count on CAPS-5
• CAPS-5 past month total score greater than or equal to 26
• 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.

You may not qualify if:

• Diagnosis of DSM-5-defined bipolar I, schizophrenia spectrum or other psychotic disorders (by MINI)
• Presence of severe psychotic symptoms such that, based on the clinical judgement of the investigator or treatment provider, treatment with an antipsychotic is required.
• 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.
• History of severe TBI as defined by the Ohio State University TBI Identification Method.
• Diagnosis of dementia or related progressive neurocognitive disorder, based on clinical records.
• 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).
• 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).
• Use of any investigational drug, MPH formulation, antipsychotics, mood stabilizers, monoamine oxidase inhibitors, stimulants, atomoxetine, or bupropion within 2 weeks of baseline.
• 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.
• A clinically significant acute or uncontrolled chronic medical/surgical illness that would contraindicate use of MPH, or a known terminal illness.
• Prior allergic reaction to any MPH formulation.
• Litigating for compensation for a psychiatric disorder outside the Veterans benefits compensation and pension process.
• Current enrollment in another interventional trial for PTSD.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (3)

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, 35233-1927, United States

RECRUITING

Tuscaloosa VA Medical Center, Tuscaloosa, AL

Tuscaloosa, Alabama, 35404-5015, United States

RECRUITING

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

Seattle, Washington, 98108-1532, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Attention Deficit Disorder with Hyperactivity; Brain Injuries, Traumatic

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Rebecca C. Hendrickson, MD PhD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca C Hendrickson, MD PhD

CONTACT

(206) 277-5054; Rebecca.Hendrickson@va.gov

Carolyn L Fort, BS

CONTACT

(206) 768-5259; carolyn.fort@va.gov

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, investigator/study clinicians, and clinical assessors (raters) are blinded to study drug until study completion for each participant.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: The study compares MPH (intervention) and PBO (control) using an aggregated N-of-1 trial design. N-of-1 clinical trials are multi-cycle, double-blinded, placebo-controlled cross-over trials based on an individual. In aggregated N-of-1 trials, data from a cohort of participants are analyzed together, often to test the efficacy of a treatment whilst controlling for the heterogeneity of response. Our design consists of 2 cycles, with each cycle including 4 weeks of MPH 10mg twice daily and 4 weeks of PBO twice daily, each followed by a 1-week washout. This provides a total of 8 weeks on active drug and 8 weeks on placebo. Order of MPH vs PBO within cycle is randomly assigned and double-blinded.

Study Record Dates

• First Submitted: March 8, 2023
• First Posted: March 20, 2023
• Study Start: February 5, 2024
• Primary Completion (Estimated): July 6, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)