Posttraumatic Stress DisorderPhase 2CREATENCT01416948
Cognitive REmediation After Trauma Exposure Trial = CREATE Trial
A Phase 2 study testing Methylphenidate Hydrochloride 20 mg and Galantamine 12 mg in people with Posttraumatic Stress Disorder and Traumatic Brain Injury, run by INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium at 7 sites in United States.
Trial summary
This study will evaluate the efficacy of methylphenidate and galantamine in the treatment of persistent cognitive symptoms associated with posttraumatic stress disorder (PTSD) and/or traumatic brain injury (TBI). Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Posttraumatic Stress Disorder, Traumatic Brain Injury
- What is being tested?
- Methylphenidate Hydrochloride 20 mg and Galantamine 12 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 7 sitesUnited States
- Study dates
- Aug 2011to Mar 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Aged 18-55 years
- Has a DSM-IV diagnosis of chronic (≥ 3 months duration) PTSD and/or a history of TBI (≥ 3 months duration) as established by the INTRuST standard TBI Screening questionnaire.
- TBI must have occurred ≥ 90 days prior to the screening visit
- With either diagnosis (i.e., PTSD or TBI), the subject must have clinically significant cognitive complaints, as indicated by a T score ≥ 60 on the postmorbid Cognitive scale of the RNBI
- Interested in receiving treatment for cognitive symptoms
- Capable of giving informed consent
Who cannot join
- Known sensitivity, or previous adverse reaction(s), to GAL or other acetylcholinesterase inhibitors such as donepezil or rivastigmine OR Known sensitivity or previous adverse reactions to MPH or other stimulant medications (e.g., dextroamphetamine, long-acting methylphenidate preparations)
- Pregnant, likely to become pregnant, or lactating (female subjects only)
- Does not speak English
- WRAT scaled score < 70
- History of glaucoma
- History of cardiac conditions (e.g., bradycardia, AV block) or history of taking medications that are associated with conduction abnormalities
Show all 21Show fewer
- History of seizure disorder (including post-traumatic epilepsy), neurosurgery, or neurodisability [Note that history of "impact seizure" is permitted]
- Lifetime history of psychotic disorder, Bipolar I, stimulant abuse or dependence, or tic disorder
- Alcohol dependence, alcohol abuse*, substance abuse, or substance dependence in the past 6 months [*Alcohol abuse will be defined as MINI diagnosis of "Alcohol Abuse" AND an AUDIT-C score of ≥ 5; Dawson, Grant, \& Stinson, 2005].
- Current active suicidal ideation, or history of actual attempt within the past 10 years
- Current severe depressive symptoms, as indicated by a score of 20 or higher on the PHQ-9
- Current (or past 2-week) use of monoamine oxidase inhibitors [Washout period of at least 2 weeks is required]
- Current (or past 2-week) use of medications that potentiate cholinergic function (i.e., other cholinesterase inhibitors or procholinergic agents), or use of over-the-counter procholinergics [Washout period of at least 2 weeks is required]
- Current (or past 2-week) use of amphetamine-type stimulants or modafinil
- Current use of any other psychotropic medication that fails to meet the stabilization criterion of a minimum of 4 weeks on the same medication(s) and dose(s)
- Prior use of any other psychotropic medication that fails to meet the washout criterion of 2 weeks
- Concurrent cognitive therapy, that will not be discontinued at least 7 days prior to the baseline visit
- Baseline ECG and/or bloodwork reveals serious illness that precludes participation or use of study medications
- Any procedure requiring general anesthesia
- History of peptic ulcer disease or GI bleed or endoscopic procedure for GERD within the last year. Subjects taking physician prescribed treatment for GERD will be allowed to participate at the discretion of the PI after discussion with the primary treating physician.
- Current (or past 2-week) use of alpha 2 adrenergic agonists such as guanfacine
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Spaulding Rehabilitation Hospital
Boston, Massachusetts, 02114
Ralph H. Johnson VA Medical Center
Charleston, South Carolina, 29401
University of Cincinnati
Cincinnati, Ohio, 45219
Duke University
Durham, North Carolina, 27710
Manchester VA Medical Center
Manchester, New Hampshire, 03104
VA San Diego Healthcare System
San Diego, California, 92161
White River Junction VA Medical Center
White River Junction, Vermont, 05009
About this study
Official title: Randomized Controlled Trial of Galantamine, Methylphenidate, and Placebo for the Treatment of Cognitive Symptoms in Patients With Traumatic Brain Injury (TBI) and/or Posttraumatic Stress Disorder (PTSD)
This study will evaluate the efficacy of methylphenidate and galantamine in the treatment of persistent cognitive symptoms associated with posttraumatic stress disorder (PTSD) and/or traumatic brain injury (TBI).
Read the detailed description
Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are prevalent in service members returning from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND). Virtually all individuals who suffer TBI (TBI) have acute cognitive effects, and a significant number have persistent symptoms. A large number of individuals with PTSD also report problems with cognition, however, little is known about the treatment of cognitive complaints in either condition and less is known about cognitive complaints in individuals with co-occurring TBI and PTSD.
There is some preclinical evidence that both the cholinergic and catecholaminergic neurotransmitter systems play important roles in cognitive function in healthy individuals as well as those with mTBI and/or PTSD. We propose to evaluate the efficacy of two pharmacotherapies, one that predominantly augments cholinergic function (galantamine [GAL]) and one that augments predominantly catecholaminergic function (methylphenidate [MPH]), for reducing cognitive symptoms in individuals with TBI and/or PTSD.
Using a double-blind, randomized, placebo controlled design, 159 individuals with TBI and/or PTSD with persistent cognitive complaints will be randomized to receive galantamine 12 mg BID, methylphenidate 20 mg BID, or placebo for 12 weeks. The primary objective is to assess the efficacy of galantamine and methylphenidate in reducing cognitive complaints in patients with PTSD and/or TBI. Secondary objectives are to assess the extent to which non-cognitive distress responds to galantamine or methylphenidate, and assess the effect that galantamine and methylphenidate have on cognitive performance.
- Being tested
- Methylphenidate Hydrochloride 20 mg, Placebo Capsule, Galantamine 12 mg
- Keywords
- Cognitive Complaints, TBI, PTSD
- Medical subject headings
- Stress Disorders, Post-Traumatic, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methylphenidate Hydrochloride 20 mgDrug
Also called Ritalin
For patients assigned to the MPH arm of the study, the drug will be initiated at 5 mg bid at week 0, and increased to 10 mg bid at week 4, and finally increased to 20 mg bid at week 8 and then held constant until the major outcome assessment at week 12. The drug will be gradually tapered during weeks 12-14. If adverse events ensue, the subject's dose can be held at the current dose (rather than proceeding with scheduled dose increases) or reduced to the previous dose. Subjects who cannot tolerate the minimum dose (5 mg bid) will be withdrawn from the study.
Placebo CapsuleDrug
For patients randomly assigned to the placebo arm of the study, placebo will be administered BID at Week 0 through Week 12. Matching placebo will be administered to match the taper period.
Galantamine 12 mgDrug
Also called Razadyne
For patients randomly assigned to the GAL arm of the study, the drug will be initiated at 4 mg bid at week 0, increased to 8 mg bid at week 4, and finally increased to 12 mg bid at week 8 and then held constant until the major outcome assessment at week 12. The drug will be gradually tapered during weeks 12-14. If adverse events ensue, the subject's dose can be held at the current dose (rather than proceeding with scheduled dose increases) or reduced to the previous dose. Subjects who cannot tolerate the minimum dose (4 mg bid) will be withdrawn from the study.
| Study group | Role | What they receive |
|---|---|---|
| Sugar Pill | Placebo comparator | Not described Receives: Drug: Placebo Capsule |
| Galantamine | Active comparator | Not described Receives: Drug: Galantamine 12 mg |
| Methylphenidate | Experimental | Not described Receives: Drug: Methylphenidate Hydrochloride 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ruff Neurobehavioral Inventory - Postmorbid Cognitive Scale
The Ruff Neurobehavioral Inventory (RNBI; Ruff \& Hibbard, 2003) is a self-report instrument for assessment of a wide range of symptoms (cognitive, emotional, and physical), as well as quality of life and daily functioning. It was designed to assess these areas in individuals who have recently been affected by an injury, illness, or other stressor. The Postmorbid Cognitive scale will be used as the primary outcome measure in this study. The Postmorbid Cognitive scale consists of 24 items assessing Attention/Concentration, Executive Functions, Learning/Memory, and Speech/Language.
Measured: Baseline through Week 12
Secondary outcomes (5)
Rivermead Postconcussion Symptom Questionnaire (RPCSQ)
The RPCSQ (N King, 1995), which can be self-administered or given by an interviewer, asks patients to rate the severity of 16 different symptoms commonly found after a mild traumatic brain injury. Patients are asked to rate the severity of each symptom over the past week and compare to the severity before their injury. This instrument will be used to determine the extent to which the broad spectrum of TBI symptoms respond to GAL and MPH.
Measured: Baseline through week 12
Patient Health Questionnaire-9 (PHQ - 9)
The PHQ - 9 (Pfizer, 1999) is the self-administered 9 item depression scale of the Patient Health Questionnaire. This instrument will be used to determine the extent to which GAL and MPH improve depressive symptoms in participants with PTSD and/or TBI.
Measured: Baseline through week 12
PTSD Checklist - Specific Event Version (PCL-S)
The PTSD Checklist - Specific Event Version (Weathers, 1993) is a 17 item self-report measure of DSM IV symptoms of PTSD in response to a specific event, used for screening and diagnosis of PTSD and monitoring symptom change during treament. This measure will be used to determine the extent to which the broad spectrum of PTSD symptoms responds to GAL and MPH.
Measured: Baseline through week 12
PreMorbid-Postmorbid Difference Score on Cognitive Scale of Ruff Neurobehavioral Inventory
This measurement will be used to determine the extent to which GAL and MPH reduce the perceived difference between subjects' premorbid and postmorbid cognitive functioning.
Measured: Baseline through 12 weeks
Neuropsychological Tests of Memory, Attention and Other Executive Functions
These measurements will be used to determine the extent to which GAL and MPH affect objective cognitive functioning in participants with PTSD and/or TBI as measured on the following neuropsychological tests: Rey Verbal Auditory Learning Test; Trail Making Test; WAIS-III Processing Speed Index and Digit Span; Digit Vigilance test; WMS-III Letter-Number Sequencing; Brief Visuospatial Memory Test-Revised; Paced Auditory Serial Addition Test; Continuous Performance Test; and D-KEFS Verbal Fluency.
Measured: Baseline through 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2011 (estimated)
- Study startAug 2011
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: The funding agency, DoD, determined that the study could not meet its enrollment numbers by the end of the grant.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress DisorderStudies of the same condition, open and under way.
- 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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium
- Sponsor type
- University, hospital or other
- Collaborators
- U.S. Army Medical Research and Development Command
- Responsible party
- Sponsor
- Investigators
- Thomas W McAllister, M.D., Principal investigator, Dartmouth-Hitchcock Medical CenterRoss Zafonte, M.D., Principal investigator, Spaulding Rehabilitation Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01416948
- Sponsor's protocol ID
- INTRuST-CREATE
- Acronym
- CREATE
- Status last verified
- Apr 2013
- First submitted
- 12 Aug 2011
- Last updated
- 26 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of Galantamine, Methylphenidate, and Placebo for the Treatment of Cognitive Symptoms in Patients With Traumatic Brain Injury (TBI) and/or Posttraumatic Stress Disorder (PTSD)
- ClinicalTrials.gov ID
- NCT01416948
- Acronym / sponsor ID
- CREATE / INTRuST-CREATE
- Keywords
- Cognitive Complaints, TBI, PTSD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The funding agency, DoD, determined that the study could not meet its enrollment numbers by the end of the grant.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical ConsortiumUniversity, hospital or other
- Collaborators
- U.S. Army Medical Research and Development Command
- Study start
- Aug 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 15 Aug 2011 (estimated)
- 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.
This study will evaluate the efficacy of methylphenidate and galantamine in the treatment of persistent cognitive symptoms associated with posttraumatic stress disorder (PTSD) and/or traumatic brain injury (TBI).
Detailed description
Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are prevalent in service members returning from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND). Virtually all individuals who suffer TBI (TBI) have acute cognitive effects, and a significant number have persistent symptoms. A large number of individuals with PTSD also report problems with cognition, however, little is known about the treatment of cognitive complaints in either condition and less is known about cognitive complaints in individuals with co-occurring TBI and PTSD.
There is some preclinical evidence that both the cholinergic and catecholaminergic neurotransmitter systems play important roles in cognitive function in healthy individuals as well as those with mTBI and/or PTSD. We propose to evaluate the efficacy of two pharmacotherapies, one that predominantly augments cholinergic function (galantamine [GAL]) and one that augments predominantly catecholaminergic function (methylphenidate [MPH]), for reducing cognitive symptoms in individuals with TBI and/or PTSD.
Using a double-blind, randomized, placebo controlled design, 159 individuals with TBI and/or PTSD with persistent cognitive complaints will be randomized to receive galantamine 12 mg BID, methylphenidate 20 mg BID, or placebo for 12 weeks. The primary objective is to assess the efficacy of galantamine and methylphenidate in reducing cognitive complaints in patients with PTSD and/or TBI. Secondary objectives are to assess the extent to which non-cognitive distress responds to galantamine or methylphenidate, and assess the effect that galantamine and methylphenidate have on cognitive performance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sugar Pill | Placebo comparator | Drug: Placebo Capsule |
| Galantamine | Active comparator | Drug: Galantamine 12 mg |
| Methylphenidate | Experimental | Drug: Methylphenidate Hydrochloride 20 mg |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Aged 18-55 years
- Has a DSM-IV diagnosis of chronic (≥ 3 months duration) PTSD and/or a history of TBI (≥ 3 months duration) as established by the INTRuST standard TBI Screening questionnaire.
- TBI must have occurred ≥ 90 days prior to the screening visit
- With either diagnosis (i.e., PTSD or TBI), the subject must have clinically significant cognitive complaints, as indicated by a T score ≥ 60 on the postmorbid Cognitive scale of the RNBI
- Interested in receiving treatment for cognitive symptoms
Key exclusion criteria (21 listed)
- Known sensitivity, or previous adverse reaction(s), to GAL or other acetylcholinesterase inhibitors such as donepezil or rivastigmine OR Known sensitivity or previous adverse reactions to MPH or other stimulant medications (e.g., dextroamphetamine, long-acting methylphenidate preparations)
- Pregnant, likely to become pregnant, or lactating (female subjects only)
- Does not speak English
- WRAT scaled score < 70
- History of glaucoma
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 |
|---|---|---|
| Methylphenidate Hydrochloride 20 mgAlso: RitalinFor patients assigned to the MPH arm of the study, the drug will be initiated at 5 mg bid at week 0, and increased to 10 mg bid at week 4, and finally increased to 20 mg bid at week 8 and then held constant until the major outcome assessment at week 12. The drug will be gradually tapered during weeks 12-14. If adverse events ensue, the subject's dose can be held at the current dose (rather than proceeding with scheduled dose increases) or reduced to the previous dose. Subjects who cannot tolerate the minimum dose (5 mg bid) will be withdrawn from the study. | Drug | Methylphenidate |
| Placebo CapsuleFor patients randomly assigned to the placebo arm of the study, placebo will be administered BID at Week 0 through Week 12. Matching placebo will be administered to match the taper period. | Drug | Sugar Pill |
| Galantamine 12 mgAlso: RazadyneFor patients randomly assigned to the GAL arm of the study, the drug will be initiated at 4 mg bid at week 0, increased to 8 mg bid at week 4, and finally increased to 12 mg bid at week 8 and then held constant until the major outcome assessment at week 12. The drug will be gradually tapered during weeks 12-14. If adverse events ensue, the subject's dose can be held at the current dose (rather than proceeding with scheduled dose increases) or reduced to the previous dose. Subjects who cannot tolerate the minimum dose (4 mg bid) will be withdrawn from the study. | Drug | Galantamine |
Primary outcome
Ruff Neurobehavioral Inventory - Postmorbid Cognitive Scale
Time frame: Baseline through Week 12
The Ruff Neurobehavioral Inventory (RNBI; Ruff \& Hibbard, 2003) is a self-report instrument for assessment of a wide range of symptoms (cognitive, emotional, and physical), as well as quality of life and daily functioning. It was designed to assess these areas in individuals who have recently been affected by an injury, illness, or other stressor. The Postmorbid Cognitive scale will be used as the primary outcome measure in this study. The Postmorbid Cognitive scale consists of 24 items assessing Attention/Concentration, Executive Functions, Learning/Memory, and Speech/Language.
5 secondary outcomes
Rivermead Postconcussion Symptom Questionnaire (RPCSQ)
Time frame: Baseline through week 12
Patient Health Questionnaire-9 (PHQ - 9)
Time frame: Baseline through week 12
PTSD Checklist - Specific Event Version (PCL-S)
Time frame: Baseline through week 12
PreMorbid-Postmorbid Difference Score on Cognitive Scale of Ruff Neurobehavioral Inventory
Time frame: Baseline through 12 weeks
Neuropsychological Tests of Memory, Attention and Other Executive Functions
Time frame: Baseline through 12 weeks
Results and safety
The study was stopped early (reason given: The funding agency, DoD, determined that the study could not meet its enrollment numbers by the end of the grant.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2013.
Related trials for Posttraumatic Stress Disorder
Not yet recruitingPhase 2
Assessing of Behavioral Risk and Response to Electromagnetic and Psychedelic Therapies
PTSD, PTSD - Post Traumatic Stress Disorder
Not yet recruiting
Multimodal Intervention for Individuals With Posttraumatic Stress Disorder (PTSD) and Hazardous Alcohol Use
Post Traumatic Stress Disorder PTSD, Hazardous Alcohol Use
Not yet recruitingPhase 2
Written Exposure Therapy Plus Adjunctive Methylphenidate Treatment for Veterans With PTSD
PTSD - Post Traumatic Stress Disorder
Recruiting
Recovering Sleep After Trauma
Post-traumatic Stress Disorder
Recruiting
Evaluating Evidenced Based Options for PTSD Treatment
PTSD - Post Traumatic Stress Disorder
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.
Thomas W McAllister, M.D. principal investigator
Dartmouth-Hitchcock Medical Center
Ross Zafonte, M.D. principal investigator
Spaulding Rehabilitation Hospital
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Methylphenidate Hydrochloride 20 mg and Galantamine 12 mg in people with Posttraumatic Stress Disorder and Traumatic Brain Injury, run by INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium at 7 sites 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 21 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: stopped early, as of the sponsor's last update on 26 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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 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?
The study was stopped early (reason given: The funding agency, DoD, determined that the study could not meet its enrollment numbers by the end of the grant.). Results are not available in the source record.
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?
Ruff Neurobehavioral Inventory - Postmorbid Cognitive Scale (time frame: Baseline through Week 12). 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 26 Apr 2013.