PTSDPhase 1/2NCT04885257
Methylphenidate for Ptsd and Stroke Veterans
A Phase 1/2 study testing Methylphenidate in people with PTSD and Stroke, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Veterans with post-traumatic stress disorder (PTSD) have an increased risk of developing ischemic stroke. Veterans enduring PTSD face difficulties in managing their PTSD severity after suffering from a stroke. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- What is being tested?
- Methylphenidate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2022to 5 May 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female Veteran of US military; signed informed consent
- Criterion A Index Trauma(s) resulting in PTSD occurred during adulthood prior to stroke
- CAPS-5 past week total score =23 at baseline visit
- Willing to refrain from antipsychotics, mood stabilizers, stimulants, and any formulation of MPH
- First-ever symptomatic ischemic stroke radiologically verified, occurring within past 1-12 months
- Females of child-bearing potential (i.e. not postmenopausal or surgically sterile) must be using a medically acceptable method of birth control and should not be pregnant nor have plans for pregnancy or breastfeeding during the study
Who cannot join
- Moderate to severe cognitive impairment (Montreal Cognitive Assessment score <16/30)
- Poor pre-stroke baseline function of a modified Rankin score >2
- Presence of any standard MRI contraindications
- Current diagnosis of DSM-5-defined bipolar disorder I, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features (MINI)
- Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 3 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
Show all 18Show fewer
- Participants must agree to abstain from illicit drugs during the study
- Increased risk of suicide that necessitates inpatient treatment or warrants additional therapy excluded by the protocol; and/or intensity of suicidal ideation (Type 4 or Type 5) or any suicidal behavior in the past 3 months on Columbia Suicide Severity Rating Scale (C-SSRS)
- Use of any investigational drug, MPH formulation, antipsychotics, mood stabilizers, monoamine oxidase inhibitors, stimulants or any medication known to be a potent (strong) cytochrome P450 subtype 3A4 inhibitor within 2 weeks of baseline
- Treatment with evidence-based trauma-focused therapy for PTSD within two weeks of baseline (if participant is receiving therapy, he/she must complete treatment prior to entering study)
- Supportive psychotherapy in process at time of Screening may be continued during the study.
- History of moderate or severe TBI as defined by the Ohio State University TBI Identification Method
- Based on investigator's clinical judgment, history of mild TBI is not excluded
- Any clinically significant, uncontrolled, or medical/surgical condition or laboratory abnormality that would contraindicate use of MPH (see Human Subjects section)
- Severe allergic reaction, bronchospasm, or hypersensitivity to any MPH formulation.
- Litigating for compensation for a psychiatric disorder. Veterans who are in the process of applying for or receiving VA service-connected disability are eligible
- Current enrollment in another intervention trial for PTSD or stroke
- Persons imprisoned, diagnosed with terminal illness, or require surrogate for consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Birmingham VA Medical Center, Birmingham, AL
Birmingham, Alabama, 35233-1927
About this study
Official title: A Randomized Placebo-controlled Trial of Methylphenidate in Veterans With a Diagnosis of Post Traumatic Stress Disorder and Recent Cerebral Stroke
Veterans with post-traumatic stress disorder (PTSD) have an increased risk of developing ischemic stroke. Veterans enduring PTSD face difficulties in managing their PTSD severity after suffering from a stroke. Currently, clinical trials in PTSD exclude patients with stroke and patients with significant premorbid psychological conditions like PTSD are usually excluded from stroke clinical trials. Methylphenidate (MPH) is a central nervous system stimulant that can improve PTSD symptoms: avoidance behaviors, social withdrawal, hyperarousal, and working memory. MPH can also improve post-stroke outcomes: mood, activities of daily living, and motor functioning. In clinical trials for PTSD or stroke, MPH has been shown to be well-tolerated with minimal adverse events. The high prevalence of PTSD in Veterans with stroke provides strong justification for development of interventions that effectively and simultaneously target both conditions. The overarching goal of our proposal is to understand how MPH improves PTSD severity in Veterans with comorbid stroke.
Read the detailed description
Veterans with post-traumatic stress disorder (PTSD) have an increased risk of developing ischemic stroke. Veterans enduring PTSD face difficulties in managing their PTSD severity after suffering from a stroke. Currently, clinical trials in PTSD exclude patients with stroke and patients with significant premorbid psychological conditions like PTSD are usually excluded from stroke clinical trials. Methylphenidate (MPH) is a central nervous system stimulant that blocks dopamine and norepinephrine transporters, selectively increasing prefrontal cortex (PFC) activity. MPH can improve PTSD symptoms: avoidance behaviors, social withdrawal, hyperarousal, and working memory. The suspected mechanism is MPH activates PFC, enhancing fear extinction and improving PTSD symptoms. MPH can also improve post-stroke outcomes: mood, activities of daily living, and motor functioning. In clinical trials for PTSD or stroke, MPH has been shown to be well-tolerated with minimal adverse events. The high prevalence of PTSD in Veterans with stroke provides strong justification for development of interventions that effectively and simultaneously target both conditions. The overarching goal of our proposal is to understand how MPH improves PTSD severity in Veterans with comorbid stroke. The purpose of the clinical trial is to evaluate the therapeutic effects on PTSD symptoms and post-stroke recovery of placebo-controlled MPH in Veterans diagnosed with PTSD and cerebral stroke.
- Being tested
- Methylphenidate, Placebo
- Keywords
- Stress Disorders, Post-Traumatic, stroke
- Medical subject headings
- Stress Disorders, Post-Traumatic, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethylphenidateDrug
Also called Concerta, Ritalin
Methylphenidate oral pill. Dosing instructions given to
PlaceboDrug
Placebo arm
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Patient with both PTSD and recent history of stroke. Placebo control arm. The frequency will be up to twice a day, with oral dosing. Receives: Drug: Placebo |
| Methylphenidate | Experimental | Patient with both PTSD and recent history of stroke. Methylphenidate active arm. The oral dosing maximum will be up to 20mg twice daily. Receives: Drug: Methylphenidate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Modified Rankin Scale at 12 Weeks
The modified Ranking scale (mRS) is a single-item, global, Likert-type scale ranging from 0-6 (higher scores mean a worse outcome) to categorize level of functional independence with comparison to pre-stroke function, accounting for activities of daily living. Participants were scored at baseline, Week 4, Week 8, Week 12, and 30 days after tapering after methylphenidate/placebo. The mean change from baseline at Week 12 for each group is reported.
Measured: From baseline to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2021
- Study start14 Jan 2022
- Primary completion5 May 2025
- Study completion5 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blind placebo-controlled trial of methylphenidate. One arm receives placebo and the other receives methylphenidate.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Chen Lin, MD, Principal investigator, Birmingham VA Medical Center, Birmingham, AL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04885257
- Sponsor's protocol ID
- MHBP-011-20F
- Other IDs
- IK2CX002104
- Status last verified
- Jun 2025
- First submitted
- 3 May 2021
- Last updated
- 22 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
McAllister TW, Zafonte R, Jain S, Flashman LA, George MS, Grant GA, He F, Lohr JB, Andaluz N, Summerall L, Paulus MP, Raman R, Stein MB. Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury. Neuropsychopharmacology. 2016 Apr;41(5):1191-8. doi: 10.1038/npp.2015.282. Epub 2015 Sep 11.
PubMed 26361060Grade C, Redford B, Chrostowski J, Toussaint L, Blackwell B. Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled study. Arch Phys Med Rehabil. 1998 Sep;79(9):1047-50. doi: 10.1016/s0003-9993(98)90169-1.
PubMed 9749682
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-controlled Trial of Methylphenidate in Veterans With a Diagnosis of Post Traumatic Stress Disorder and Recent Cerebral Stroke
- ClinicalTrials.gov ID
- NCT04885257
- Acronym / sponsor ID
- MHBP-011-20F
- Keywords
- Stress Disorders, Post-Traumatic, stroke
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 14 Jan 2022 (actual)
- Primary completion
- 5 May 2025 (actual)
- Study completion
- 5 May 2025 (actual)
- First posted
- 13 May 2021 (actual)
- Results
- Posted 22 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Veterans with post-traumatic stress disorder (PTSD) have an increased risk of developing ischemic stroke. Veterans enduring PTSD face difficulties in managing their PTSD severity after suffering from a stroke. Currently, clinical trials in PTSD exclude patients with stroke and patients with significant premorbid psychological conditions like PTSD are usually excluded from stroke clinical trials. Methylphenidate (MPH) is a central nervous system stimulant that can improve PTSD symptoms: avoidance behaviors, social withdrawal, hyperarousal, and working memory. MPH can also improve post-stroke outcomes: mood, activities of daily living, and motor functioning. In clinical trials for PTSD or stroke, MPH has been shown to be well-tolerated with minimal adverse events. The high prevalence of PTSD in Veterans with stroke provides strong justification for development of interventions that effectively and simultaneously target both conditions. The overarching goal of our proposal is to understand how MPH improves PTSD severity in Veterans with comorbid stroke.
Detailed description
Veterans with post-traumatic stress disorder (PTSD) have an increased risk of developing ischemic stroke. Veterans enduring PTSD face difficulties in managing their PTSD severity after suffering from a stroke. Currently, clinical trials in PTSD exclude patients with stroke and patients with significant premorbid psychological conditions like PTSD are usually excluded from stroke clinical trials. Methylphenidate (MPH) is a central nervous system stimulant that blocks dopamine and norepinephrine transporters, selectively increasing prefrontal cortex (PFC) activity. MPH can improve PTSD symptoms: avoidance behaviors, social withdrawal, hyperarousal, and working memory. The suspected mechanism is MPH activates PFC, enhancing fear extinction and improving PTSD symptoms. MPH can also improve post-stroke outcomes: mood, activities of daily living, and motor functioning. In clinical trials for PTSD or stroke, MPH has been shown to be well-tolerated with minimal adverse events. The high prevalence of PTSD in Veterans with stroke provides strong justification for development of interventions that effectively and simultaneously target both conditions. The overarching goal of our proposal is to understand how MPH improves PTSD severity in Veterans with comorbid stroke. The purpose of the clinical trial is to evaluate the therapeutic effects on PTSD symptoms and post-stroke recovery of placebo-controlled MPH in Veterans diagnosed with PTSD and cerebral stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind placebo-controlled trial of methylphenidate. One arm receives placebo and the other receives methylphenidate.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPatient with both PTSD and recent history of stroke. Placebo control arm. The frequency will be up to twice a day, with oral dosing. |
| Methylphenidate | Experimental | Drug: MethylphenidatePatient with both PTSD and recent history of stroke. Methylphenidate active arm. The oral dosing maximum will be up to 20mg twice daily. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female Veteran of US military; signed informed consent
- Criterion A Index Trauma(s) resulting in PTSD occurred during adulthood prior to stroke
- CAPS-5 past week total score =23 at baseline visit
- Willing to refrain from antipsychotics, mood stabilizers, stimulants, and any formulation of MPH
- First-ever symptomatic ischemic stroke radiologically verified, occurring within past 1-12 months
Key exclusion criteria (18 listed)
- Moderate to severe cognitive impairment (Montreal Cognitive Assessment score <16/30)
- Poor pre-stroke baseline function of a modified Rankin score >2
- Presence of any standard MRI contraindications
- Current diagnosis of DSM-5-defined bipolar disorder I, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features (MINI)
- Diagnosis of moderate or severe substance use disorder (except for caffeine and nicotine) during the preceding 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethylphenidateAlso: Concerta, RitalinMethylphenidate oral pill. Dosing instructions given to | Drug | Methylphenidate |
| PlaceboPlacebo arm | Drug | Placebo |
Primary outcome
Change in Modified Rankin Scale at 12 Weeks
Time frame: From baseline to Week 12
The modified Ranking scale (mRS) is a single-item, global, Likert-type scale ranging from 0-6 (higher scores mean a worse outcome) to categorize level of functional independence with comparison to pre-stroke function, accounting for activities of daily living. Participants were scored at baseline, Week 4, Week 8, Week 12, and 30 days after tapering after methylphenidate/placebo. The mean change from baseline at Week 12 for each group is reported.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26361060McAllister TW, Zafonte R, Jain S, Flashman LA, George MS, Grant GA, He F, Lohr JB, Andaluz N, Summerall L, Paulus MP, Raman R, Stein MB. Randomized Placebo-Controlled Trial of Methylphenidate or Galantamine for Persistent Emotional and Cognitive Symptoms Associated with PTSD and/or Traumatic Brain Injury. Neuropsychopharmacology. 2016 Apr;41(5):1191-8. doi: 10.1038/npp.2015.282. Epub 2015 Sep 11.
- Background: PubMed 9749682Grade C, Redford B, Chrostowski J, Toussaint L, Blackwell B. Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled study. Arch Phys Med Rehabil. 1998 Sep;79(9):1047-50. doi: 10.1016/s0003-9993(98)90169-1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chen Lin, MD principal investigator
Birmingham VA Medical Center, Birmingham, AL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Methylphenidate in people with PTSD and Stroke, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Modified Rankin Scale at 12 Weeks (time frame: From baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04885257, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.