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Methylphenidate for Ptsd and Stroke Veterans

Primary Purpose

PTSD, Stroke

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Methylphenidate

Placebo

About this trial

This is an interventional treatment trial for PTSD focused on measuring Stress Disorders, Post-Traumatic, stroke

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female Veteran of US military; signed informed consent
Criterion A Index Trauma(s) resulting in PTSD occurred during adulthood prior to stroke
PTSD defined by MINI International Neuropsychiatric Inventory (MINI) for DSM-5
CAPS-5 past week total score =27 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

Exclusion Criteria:

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.
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

Sites / Locations

Birmingham VA Medical Center, Birmingham, ALRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Methylphenidate

Arm Description

Patient with both PTSD and recent history of stroke. Placebo control arm. The frequency will be up to twice a day, with oral dosing.

Patient with both PTSD and recent history of stroke. Methylphenidate active arm. The oral dosing maximum will be up to 20mg twice daily.

Outcomes

Primary Outcome Measures

Clinician-Administered Post-traumatic stress disorder scale

Structured measure used to confirm the threshold for PTSD symptoms and assess symptom severity. Total symptom severity score is calculated by summing severity scores for 20 PTSD symptoms. Each symptom can score between 0-4, with a range from 0 to 80. Higher scores indicate more severe symptoms.

Secondary Outcome Measures

Modified Rankin Scale

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.

Full Information

NCT ID

NCT04885257

First Posted

May 3, 2021

Last Updated

December 21, 2022

Sponsor

VA Office of Research and Development

1. Study Identification

Unique Protocol Identification Number

NCT04885257

Brief Title

Methylphenidate for Ptsd and Stroke Veterans

Official Title

A Randomized Placebo-controlled Trial of Methylphenidate in Veterans With a Diagnosis of Post Traumatic Stress Disorder and Recent Cerebral Stroke.

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

January 14, 2022 (Actual)

Primary Completion Date

September 30, 2026 (Anticipated)

Study Completion Date

September 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

PTSD, Stroke

Keywords

Stress Disorders, Post-Traumatic, stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Study personnel and participants will be blinded to the treatment (placebo vs methylphenidate).

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Patient with both PTSD and recent history of stroke. Placebo control arm. The frequency will be up to twice a day, with oral dosing.

Arm Title

Methylphenidate

Arm Type

Experimental

Arm Description

Patient with both PTSD and recent history of stroke. Methylphenidate active arm. The oral dosing maximum will be up to 20mg twice daily.

Intervention Type

Drug

Intervention Name(s)

Methylphenidate

Other Intervention Name(s)

Concerta, Ritalin

Intervention Description

Methylphenidate oral pill. Dosing instructions given to

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo arm

Primary Outcome Measure Information:

Title

Clinician-Administered Post-traumatic stress disorder scale

Description

Time Frame

through study completion, an average of 6 months

Secondary Outcome Measure Information:

Title

Modified Rankin Scale

Description

Time Frame

through study completion, an average of 6 months

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female Veteran of US military; signed informed consent Criterion A Index Trauma(s) resulting in PTSD occurred during adulthood prior to stroke PTSD defined by MINI International Neuropsychiatric Inventory (MINI) for DSM-5 CAPS-5 past week total score =27 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 Exclusion Criteria: 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. 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chen Lin, MD

Phone

(205) 933-8101

Chen.Lin@va.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chen Lin, MD

Organizational Affiliation

Birmingham VA Medical Center, Birmingham, AL

Official's Role

Principal Investigator

Facility Information:

Facility Name

Birmingham VA Medical Center, Birmingham, AL

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35233

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chen Lin, MD

Phone

205-933-8101

Chen.Lin@va.gov

First Name & Middle Initial & Last Name & Degree

Chen Lin, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26361060

Citation

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.

Results Reference

result

PubMed Identifier

9749682

Citation

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.

Results Reference

result

Learn more about this trial

Methylphenidate for Ptsd and Stroke Veterans

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