Cognitive REmediation After Trauma Exposure Trial = CREATE Trial (CREATE)
|ClinicalTrials.gov Identifier: NCT01416948|
Recruitment Status : Terminated (The funding agency, DoD, determined that the study could not meet its enrollment numbers by the end of the grant.)
First Posted : August 15, 2011
Last Update Posted : April 26, 2013
|Condition or disease||Intervention/treatment||Phase|
|Posttraumatic Stress Disorder Traumatic Brain Injury||Drug: Methylphenidate Hydrochloride 20 mg Drug: Placebo Capsule Drug: Galantamine 12 mg||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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)|
|Study Start Date :||August 2011|
|Primary Completion Date :||March 2013|
|Study Completion Date :||March 2013|
|Placebo Comparator: Sugar Pill||
Drug: Placebo Capsule
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.
|Active Comparator: Galantamine||
Drug: Galantamine 12 mg
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.
Other Name: Razadyne
Drug: Methylphenidate Hydrochloride 20 mg
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.
Other Name: Ritalin
- 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.
- Rivermead Postconcussion Symptom Questionnaire (RPCSQ) [ Time Frame: Baseline through week 12 ]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.
- Patient Health Questionnaire-9 (PHQ - 9) [ Time Frame: Baseline through week 12 ]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.
- PTSD Checklist - Specific Event Version (PCL-S) [ Time Frame: Baseline through week 12 ]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.
- PreMorbid-Postmorbid Difference Score on Cognitive Scale of Ruff Neurobehavioral Inventory [ Time Frame: Baseline through 12 weeks ]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.
- Neuropsychological Tests of Memory, Attention and Other Executive Functions [ Time Frame: Baseline through 12 weeks ]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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01416948
|United States, California|
|VA San Diego Healthcare System|
|San Diego, California, United States, 92161|
|United States, Massachusetts|
|Spaulding Rehabilitation Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, New Hampshire|
|Manchester VA Medical Center|
|Manchester, New Hampshire, United States, 03104|
|United States, North Carolina|
|Durham, North Carolina, United States, 27710|
|United States, Ohio|
|University of Cincinnati|
|Cincinnati, Ohio, United States, 45219|
|United States, South Carolina|
|Ralph H. Johnson VA Medical Center|
|Charleston, South Carolina, United States, 29401|
|United States, Vermont|
|White River Junction VA Medical Center|
|White River Junction, Vermont, United States, 05009|
|Principal Investigator:||Thomas W McAllister, M.D.||Dartmouth-Hitchcock Medical Center|
|Principal Investigator:||Ross Zafonte, M.D.||Spaulding Rehabilitation Hospital|