Methylphenidate for Ptsd and Stroke Veterans

NCT04885257 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MHBP-011-20FIK2CX002104
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

PTSD; Stroke

Keywords

Stress Disorders, Post-Traumatic; stroke

Outcome Measures

Primary Outcomes (1)

• 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.

  From baseline to Week 12

Study Arms (2)

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.

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.

Drug: Methylphenidate

Interventions

Methylphenidate DRUG

Methylphenidate oral pill. Dosing instructions given to

Also known as: Concerta, Ritalin

Methylphenidate

Placebo DRUG

Placebo arm

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Birmingham VA Medical Center, Birmingham, AL

Birmingham, Alabama, 35233-1927, United States

Location

Related Publications (2)

• 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.

  PMID: 26361060 BACKGROUND

• Grade 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.

  PMID: 9749682 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Stroke

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Research Compliance Officer
• Organization: Birmingham VA Medical Center

latanya.higginbottom@va.gov

205-933-8101

Study Officials

• Chen Lin, MD

  Birmingham VA Medical Center, Birmingham, AL

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study personnel and participants will be blinded to the treatment (placebo vs methylphenidate).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: double-blind placebo-controlled trial of methylphenidate. One arm receives placebo and the other receives methylphenidate.

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: May 13, 2021
• Study Start: January 14, 2022
• Primary Completion: May 5, 2025
• Study Completion: May 5, 2025
• Last Updated: June 22, 2025
• Results First Posted: June 22, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)