PTSD - Post Traumatic Stress DisorderPhase 2WET+MPHNCT07904000
Written Exposure Therapy Plus Adjunctive Methylphenidate Treatment for Veterans With PTSD
A Phase 2 study testing Written Exposure Therapy (WET) and methylphenidate (MPH) in people with PTSD - Post Traumatic Stress Disorder, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Many Veterans with post-traumatic stress disorder (PTSD) do not fully benefit from the best current treatments, some of which focus on helping the brain regulate trauma memories. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- PTSD - Post Traumatic Stress Disorder
- What is being tested?
- Written Exposure Therapy (WET) and methylphenidate (MPH)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 138 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2027to 30 Sep 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Veteran
- Current post-traumatic stress disorder (PTSD) symptoms
- Medically healthy
- Body weight of ≥ 120 pounds (55 kilograms)
- Participants must be able to participate and willing to give written informed consent and to comply with the study restrictions
Who cannot join
- Major medical issues
- Medical conditions that could alter the absorption, metabolism or elimination of study drug
- Family history of sudden death or ventricular arrhythmia
- History of glaucoma
- History, including family history, of motor tic or diagnosis of Tourette's syndrome
- Pregnancy or lactation
Show all 24Show fewer
- Lifetime history of a chronic psychotic disorder or bipolar disorder type I
- Lifetime history of stimulant use disorder
- Current moderate or severe substance use disorder for any other substances
- High suicidal risk
- Marked anxiety, tension, or agitation, based on clinical observation, that is not due to an outside identifiable, transient, or modifiable cause
- Unable to abstain from alcohol the evening before or day of study drug administration
- History of a traumatic brain injury (TBI) resulting in loss of consciousness for more than 30 minutes
- Drugs of abuse as determined by a positive urine test, excepting THC
- Current use of any psychotropic medication that has not been at a stable dose
- Current or recent use of a monoamine oxidase inhibitor or any other medication deemed by the study physician to exhibit an unsafe interaction with methylphenidate (MPH)
- Past intolerance to methylphenidate (MPH) or any other psychostimulant
- Current uncontrolled hypertension
- Current heavy smoker and/or heavy caffeine consumption and unable to limit on study days
- Abnormal Electrocardiogram, per study physician
- Participation in a clinical trial with an investigational drug or a device within 30 days prior to dosing.
- Concurrent participation in an evidence-based behavioral therapy treatment for PTSD
- Volunteers who are unable to understand the informed consent form(s) and complete the study procedures including clinical testing
- Any other reason, per study investigators, that would put the participant at undue risk or interfere with the conduct of the study per protocol
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Victoria B Risbrough contact
United States1 site
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161-0002
Carl J Stepnowsky, Jr., PhD, (858) 642-1240, Carl.Stepnowsky@va.gov
Andrea Townsend, PhD
About this study
Official title: Enhancing Written Exposure Therapy in Veterans With Posttraumatic Stress: Clinical, Physiological and Behavioral Markers of Adjunctive Methylphenidate Treatment
Many Veterans with post-traumatic stress disorder (PTSD) do not fully benefit from the best current treatments, some of which focus on helping the brain regulate trauma memories. While therapies like Prolonged Exposure and Written Exposure Therapy work for many, about half of Veterans still struggle with symptoms even after treatment. Research suggests that methylphenidate (commonly known as Ritalin), a safe and widely used medication, may improve PTSD symptoms and related mechanisms. This project will test whether adding methylphenidate to Written Exposure Therapy will result in a greater reduction in PTSD symptoms compared to Written Exposure Therapy alone. The investigators will also study body and behavior markers to better understand how and why some Veterans respond to treatment. If successful, this approach could give providers a new, practical tool to improve recovery from PTSD. Ultimately, this work could lead to more personalized, effective care for Veterans, helping them return to fuller and healthier lives.
Read the detailed description
There is a critical need for novel, and efficacious treatment strategies for post-traumatic stress disorder (PTSD) in Veterans. Gold standard treatments at the VA include evidence-based therapies that leverage fear extinction mechanisms such as Prolonged Exposure and Written Exposure Therapy (WET). Although these treatments are effective, ~50% of Veterans do not show remission after treatment, indicating efforts to further enhance treatment efficacy are critical. Preclinical, translational, and clinical studies support the potential success of using methylphenidate (MPH; Ritalin) to improve PTSD symptoms and augment fear extinction. However, methylphenidate (MPH) has not been tested as an adjunctive treatment for exposure-based therapy (or any therapy) in those with PTSD. This project aims to (1) conduct a Phase 2a randomized controlled trial (RCT) of MPH to assess initial safety, tolerability, and potential to enhance efficacy of Written Exposure Therapy, and (2) to identify physiological and behavioral markers of treatment response. If successful, this work will provide clinically actionable information on the feasibility and efficacy of a scalable, mechanism-informed enhancement to behavioral therapies for PTSD in Veterans, supporting more efficient VA care delivery, precision medicine approaches, and improved clinical outcomes.
This study evaluates the efficacy of WET plus MPH (WET+MPH) versus WET plus placebo (WET+PBO) to treat Veterans with PTSD. Specifically, this design tests the ability of serial, acute, pre-session doses of 40mg of MPH, relative to PBO, to augment PTSD symptom recovery in the context of Written Exposure Therapy, using a double-blind, placebo-controlled, randomized controlled trial design in n=138 Veterans. The primary objective is to assess PTSD symptom reduction, hypothesizing superior outcomes with WET+MPH. Additional aims examine safety and tolerability of WET+MPH and psychophysiological markers of fear extinction learning. The investigators expect that measures of safety and tolerability will be comparable across groups, and that WET+MPH will enhance extinction learning compared to WET+PBO.
This study will advance our mechanistic understanding of therapeutic change by incorporating validated clinical, behavioral, and physiological assessments to enable precise characterization of how MPH alters learning processes central to PTSD recovery.
- Conditions
- PTSD - Post Traumatic Stress Disorder
- Being tested
- Written Exposure Therapy (WET), methylphenidate (MPH), placebo (PBO)
- Keywords
- Post Traumatic Stress Disorder, methylphenidate, Written Exposure Therapy, fear extinction, Veteran
- Medical subject headings
- Combat Disorders, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Written Exposure Therapy (WET)Behavioural
WET will administered per manualized protocol, either in-person or via telehealth technology
methylphenidate (MPH)Drug
Also called Ritalin
active medication
placebo (PBO)Drug
non-active medication
| Study group | Role | What they receive |
|---|---|---|
| WET+MPH | Experimental | Written Exposure Therapy plus methylphenidate (MPH 40mg) Receives: Behavioral: Written Exposure Therapy (WET); Drug: methylphenidate (MPH) |
| WET+PBO | Active comparator | Written Exposure Therapy plus placebo (PBO) Receives: Behavioral: Written Exposure Therapy (WET); Drug: placebo (PBO) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Post-traumatic stress disorder (PTSD) symptom severity will be measured via the diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), where the CAPS-5 score range = 0 - 80. Higher scores = more severe PTSD symptoms.
Measured: Change from pre-treatment to 4-weeks post-treatment
Secondary outcomes (3)
Adverse Event Checklist (AE Checklist)
The Adverse Event Checklist (AE Checklist) is a list of standard complaints that includes frequent side effects of methylphenidate. The AE Checklist will be used to guide evaluation of adverse events and to help determine AE occurrence, AE-related medication dose adjustments, AE-related medication discontinuation, or AE-related study withdrawal. Greater number of items endorsed = greater occurrence of adverse events.
Measured: The Modified-FIBSER is collected at every WET session (sessions 1-5), over a timeframe of up to 10 weeks
Modified Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) Scale
Self-rated severity of within session side effects as measured by a Modified Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) Scale . The FIBSER scale is a self-report measure providing 3 global ratings of frequency, intensity, and burden to assess side effects of pharmacotherapy. The scale was modified to measure perceived within-session medication side-effects and the degree to which they interfere with Written Exposure Therapy session goals. The M-FIBSER will be used to guide evaluation of side effects and to help determine study medication tolerability. The M-FIBSER score has three items ranging 0 - 6. Higher scores = more severe frequent/severe/or burdensome side effects.
Measured: The Modified-FIBSER is collected at every WET session (sessions 1-5), over a timeframe of up to 10 weeks
Fear Extinction learning
Fear potentiated startle is a behavioral indicator of conditioned fear responses, collected during extinction, measured using eyeblink electromyogram (EMG) response. Extinction learning (change in response to conditioned fear cue) as measured by EMG during extinction training session is the secondary outcome measure. EMG responses are measured as arbitrary digital units 0-4095 AU (0.5 mV input unit=2500 mV output unit).
Measured: Change from pre-treatment to 4-weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2026
- Study start1 Jul 2027 (estimated)
- Primary completion30 Sep 2030 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSD - Post Traumatic Stress DisorderStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two group randomized controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Andrea Townsend, PhD, Principal investigator, VA San Diego Healthcare System, San Diego, CAVictoria B Risbrough, Principal investigator, VA San Diego Healthcare System, San Diego, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07904000
- Sponsor's protocol ID
- MHBP-002-26S
- Other IDs
- I01RD001571-05A2
- Acronym
- WET+MPH
- Status last verified
- Oct 2026
- First submitted
- 30 Sep 2026
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon completion of the study and no later than 6 months after breaking the blind the data will be uploaded to the VA CESAMH Biorepository. The VA CESAMH Biorepository will house the data for future analyses. Requests for data will be approved through the Biorepository Board and with appropriate Data Use Agreement across the VA and requesting institution. US-based academic and Veteran Affairs institutions may apply for data access.
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing Written Exposure Therapy in Veterans With Posttraumatic Stress: Clinical, Physiological and Behavioral Markers of Adjunctive Methylphenidate Treatment
- ClinicalTrials.gov ID
- NCT07904000
- Acronym / sponsor ID
- WET+MPH / MHBP-002-26S
- Conditions
- PTSD - Post Traumatic Stress Disorder
- Keywords
- Post Traumatic Stress Disorder, methylphenidate, Written Exposure Therapy, fear extinction, Veteran
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Jul 2027 (estimated)
- Primary completion
- 30 Sep 2030 (estimated)
- Study completion
- 30 Sep 2030 (estimated)
- First posted
- 29 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many Veterans with post-traumatic stress disorder (PTSD) do not fully benefit from the best current treatments, some of which focus on helping the brain regulate trauma memories. While therapies like Prolonged Exposure and Written Exposure Therapy work for many, about half of Veterans still struggle with symptoms even after treatment. Research suggests that methylphenidate (commonly known as Ritalin), a safe and widely used medication, may improve PTSD symptoms and related mechanisms. This project will test whether adding methylphenidate to Written Exposure Therapy will result in a greater reduction in PTSD symptoms compared to Written Exposure Therapy alone. The investigators will also study body and behavior markers to better understand how and why some Veterans respond to treatment. If successful, this approach could give providers a new, practical tool to improve recovery from PTSD. Ultimately, this work could lead to more personalized, effective care for Veterans, helping them return to fuller and healthier lives.
Detailed description
There is a critical need for novel, and efficacious treatment strategies for post-traumatic stress disorder (PTSD) in Veterans. Gold standard treatments at the VA include evidence-based therapies that leverage fear extinction mechanisms such as Prolonged Exposure and Written Exposure Therapy (WET). Although these treatments are effective, ~50% of Veterans do not show remission after treatment, indicating efforts to further enhance treatment efficacy are critical. Preclinical, translational, and clinical studies support the potential success of using methylphenidate (MPH; Ritalin) to improve PTSD symptoms and augment fear extinction. However, methylphenidate (MPH) has not been tested as an adjunctive treatment for exposure-based therapy (or any therapy) in those with PTSD. This project aims to (1) conduct a Phase 2a randomized controlled trial (RCT) of MPH to assess initial safety, tolerability, and potential to enhance efficacy of Written Exposure Therapy, and (2) to identify physiological and behavioral markers of treatment response. If successful, this work will provide clinically actionable information on the feasibility and efficacy of a scalable, mechanism-informed enhancement to behavioral therapies for PTSD in Veterans, supporting more efficient VA care delivery, precision medicine approaches, and improved clinical outcomes.
This study evaluates the efficacy of WET plus MPH (WET+MPH) versus WET plus placebo (WET+PBO) to treat Veterans with PTSD. Specifically, this design tests the ability of serial, acute, pre-session doses of 40mg of MPH, relative to PBO, to augment PTSD symptom recovery in the context of Written Exposure Therapy, using a double-blind, placebo-controlled, randomized controlled trial design in n=138 Veterans. The primary objective is to assess PTSD symptom reduction, hypothesizing superior outcomes with WET+MPH. Additional aims examine safety and tolerability of WET+MPH and psychophysiological markers of fear extinction learning. The investigators expect that measures of safety and tolerability will be comparable across groups, and that WET+MPH will enhance extinction learning compared to WET+PBO.
This study will advance our mechanistic understanding of therapeutic change by incorporating validated clinical, behavioral, and physiological assessments to enable precise characterization of how MPH alters learning processes central to PTSD recovery.
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
- Two group randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| WET+MPH | Experimental | Behavioral: Written Exposure Therapy (WET), Drug: methylphenidate (MPH)Written Exposure Therapy plus methylphenidate (MPH 40mg) |
| WET+PBO | Active comparator | Behavioral: Written Exposure Therapy (WET), Drug: placebo (PBO)Written Exposure Therapy plus placebo (PBO) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Veteran
- Current post-traumatic stress disorder (PTSD) symptoms
- Medically healthy
- Body weight of ≥ 120 pounds (55 kilograms)
- Participants must be able to participate and willing to give written informed consent and to comply with the study restrictions
Key exclusion criteria (24 listed)
- Major medical issues
- Medical conditions that could alter the absorption, metabolism or elimination of study drug
- Family history of sudden death or ventricular arrhythmia
- History of glaucoma
- History, including family history, of motor tic or diagnosis of Tourette's syndrome
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 |
|---|---|---|
| Written Exposure Therapy (WET)WET will administered per manualized protocol, either in-person or via telehealth technology | Behavioural | WET+MPH, WET+PBO |
| methylphenidate (MPH)Also: Ritalinactive medication | Drug | WET+MPH |
| placebo (PBO)non-active medication | Drug | WET+PBO |
Primary outcome
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
Time frame: Change from pre-treatment to 4-weeks post-treatment
Post-traumatic stress disorder (PTSD) symptom severity will be measured via the diagnostic interview, the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), where the CAPS-5 score range = 0 - 80. Higher scores = more severe PTSD symptoms.
3 secondary outcomes
Adverse Event Checklist (AE Checklist)
Time frame: The Modified-FIBSER is collected at every WET session (sessions 1-5), over a timeframe of up to 10 weeks
Modified Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) Scale
Time frame: The Modified-FIBSER is collected at every WET session (sessions 1-5), over a timeframe of up to 10 weeks
Fear Extinction learning
Time frame: Change from pre-treatment to 4-weeks post-treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: Yes. Upon completion of the study and no later than 6 months after breaking the blind the data will be uploaded to the VA CESAMH Biorepository. The VA CESAMH Biorepository will house the data for future analyses. Requests for data will be approved through the Biorepository Board and with appropriate Data Use Agreement across the VA and requesting institution. US-based academic and Veteran Affairs institutions may apply for data access.
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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.
Victoria B Risbrough contact
Andrea Townsend, PhD principal investigator
VA San Diego Healthcare System, San Diego, CA
Victoria B Risbrough principal investigator
VA San Diego Healthcare System, San Diego, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Written Exposure Therapy (WET) and methylphenidate (MPH) in people with PTSD - Post Traumatic Stress Disorder, 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 5 inclusion and 24 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: opening soon, as of the sponsor's last update on 29 Oct 2026. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrea Townsend, PhD ((858) 552-8585, andrea.townsend@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) (time frame: Change from pre-treatment to 4-weeks post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Oct 2026.