Rivastigmine Patch in Veterans With Cognitive Impairment Following TBI (RIVET)
|Traumatic Brain Injury Cognitive Impairment||Drug: Rivastigmine Transdermal Patch||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Rivastigmine Patch in Veterans With Cognitive Impairment Following TBI|
- Number of Participants With Demonstrated Improvement From Baseline on the Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall [ Time Frame: week 12 ]The primary efficacy measure was the Hopkins Verbal Learning Test - Revised (HVLT-R) Total Recall Index. HVLT-R was administered at screen, baseline, weeks 4, and 12. The HVLT is a measure that assesses verbal learning and memory. Alternate versions of the HVLT-R were administered at each of the different time points. The test consists of 12 words which are read to participants for three consecutive trials, each trial followed by free recall. The Total Recall score is the total number of words recalled over the three trials. The primary endpoint evaluation was to compare the proportion of patients who demonstrated improvement from baseline on the HVLT-R Total Recall of at least 5-word and at week 12 between the treatment and placebo group.
- Twelve-week Change in University of California San Diego Performance-based Skills Assessment - Brief (UPSA-B) [ Time Frame: 12 weeks ]UPSA-B is a validated performance-based measure to evaluate the impact of rivastigmine-mediated memory improvements on the ability to perform tasks required for day-to-day functioning in two subdomains of financial management and communication. The scale goes from (0-100) and high score indicates better functions. Comparison of difference in mean changes of UPSA-B from baseline to 12-week follow-up between two groups.
- Twelve-week Change in The PTSD Symptom Checklist-Military Version (PCL-M) [ Time Frame: 12 week ]
PCL-M is a validated 17-item self-report measure of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) symptoms of PTSD.The PCL-M asks about problems in response to "stressful military experiences." Items are rated on a 5-point scale ranging from 1 ("not at all") to 5 ("extremely"). Higher score indicates more stressful.
Comparison of difference in mean changes of PCL-M from baseline to 12-week follow-up between two groups.
- Twelve-week Change in Beck Depression Inventory-II (BDI-II) [ Time Frame: 12 week ]
Beck Depression Inventory-II (BDI-II) is a validated 21-question multiple-choice self-report inventory, one of the most widely used instruments for measuring the severity of depressive symptoms. Each answer is scored on a scale value of 0 to 3. Higher score indicates more severe depression.
To compare the differences in mean changes of BDI-II between two groups using two groups from baseline to week 12.
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||September 2017|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Rivastigmine transdermal patch
Drug: Rivastigmine Transdermal Patch
Other Name: Cholinesterase Inhibitor
Placebo Comparator: Placebo
Drug: Rivastigmine Transdermal Patch
Other Name: Cholinesterase Inhibitor
Traumatic brain injury (TBI) represents one of the most significant health risks related to military duty; rapidly becoming the "signature injury" of the Iraq and Afghanistan conflicts. TBI patients often experience multiple cognitive problems, with disturbances in memory, attention, and executive functions among the most common. Disturbances in memory as well as attention are particularly problematic, as disruption of these relatively basic cognitive functions may exacerbate or cause additional disturbances in executive function, communication and other more complex cognitive domains. These cognitive deficits, especially when memory is affected, significantly impact day-to-day functioning and are the source of lingering disability and distress to the affected individuals. However, despite advances made in TBI care, treatment of cognitive deficits in TBI lag behind, forcing clinicians to provide treatment without the guidance of evidence-based scientific data. This proposal aims to begin the process of providing clinicians with evidence-based guidelines for pharmacological management of Veterans with TBI suffering from persistent cognitive deficits following their injuries. This aim will be accomplished by conducting a clinical trial in Veterans suffering from moderate to severe posttraumatic memory impairment following TBI. Specifically, this proposal will evaluate the efficacy and safety of rivastigmine transdermal patch, an intermediate-acting cholinesterase inhibitor, in this population.
The investigators hypothesize that rivastigmine transdermal patch will be more effective than, and equally safe as, placebo in the treatment of moderate to severe posttraumatic memory impairment in Veterans with TBI when tested in a randomized, multi-site, parallel design, placebo-controlled trial, at a 12-week endpoint. The exploratory hypothesis states that compared to placebo, rivastigmine patch will be more effective and equally safe in the treatment of patients who will continue in a randomized, placebo-controlled phase for a total of 26 weeks. To test these hypotheses we will evaluate the effect and the safety of rivastigmine 9.5 mg/24 hours (10cm2) transdermal patch in 138 Veterans who meet or exceed the criteria for closed, non-penetrating, mild TBI and who present at baseline with moderate to severe memory impairment. Memory impairment will be defined as a Total Recall index (Trials 1-3) of the Hopkins Verbal Learning Test-Revised (HVLT-R) that is at least 25% lower than the intelligence-adjusted expected score, as assessed by the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Information and Vocabulary subtests. The study consists of a screening period, one-week single-blind, placebo run-in phase, and a 12-week double-blind acute treatment phase (Phase I). Subjects will be randomized 1:1 to rivastigmine transdermal patch 9.5mg/24 hours (10cm2) or matching placebo. During Phase I, there will be an initial 4-week titration period followed by an 8-week continuation phase. Following the 12-week acute treatment phase, randomized patients will continue in the double-blind phase (Phase II) for additional 14 weeks or until study treatment period ends. Recruitment stage ended 2.25.16. Efficacy will be determined by comparing the proportion of patients in each treatment group who are classified as responders at week 12. Secondary measure of functional capacity assessing the impact of memory improvement on real-world functioning, other measures of cognitive domains affected in TBI, namely attention, working and episodic memory and executive functions, as well as measures of mood and quality of life will be examined. Study findings will contribute to the body of evidence needed to establish standards of care for Veterans with posttraumatic memory impairment and other cognitive deficits.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01670526
|United States, California|
|VA San Diego Healthcare System, San Diego, CA|
|San Diego, California, United States, 92161|
|United States, Florida|
|Miami VA Healthcare System, Miami, FL|
|Miami, Florida, United States, 33125|
|James A. Haley Veterans' Hospital, Tampa, FL|
|Tampa, Florida, United States, 33612|
|United States, Illinois|
|Edward Hines Jr. VA Hospital, Hines, IL|
|Hines, Illinois, United States, 60141-5000|
|United States, Nebraska|
|Lincoln Community-Based Outpatient Clinic, Lincoln, NE|
|Lincoln, Nebraska, United States, 68510|
|United States, South Carolina|
|Ralph H. Johnson VA Medical Center, Charleston, SC|
|Charleston, South Carolina, United States, 29401-5799|
|United States, Texas|
|Michael E. DeBakey VA Medical Center, Houston, TX|
|Houston, Texas, United States, 77030|
|United States, Utah|
|VA Salt Lake City Health Care System, Salt Lake City, UT|
|Salt Lake City, Utah, United States, 84148|
|Principal Investigator:||Olga Brawman-Mintzer, MD||Ralph H. Johnson VA Medical Center, Charleston, SC|