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Multicenter Evaluation of Memory Remediation After TBI With Donepezil (MEMRI-TBI-D)

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ClinicalTrials.gov Identifier: NCT02255799
Recruitment Status : Active, not recruiting
First Posted : October 3, 2014
Last Update Posted : December 28, 2018
Sponsor:
Collaborators:
Spaulding Rehabilitation Hospital
Albert Einstein Healthcare Network
Indiana University
Craig Hospital
TIRR Memorial Hermann
Information provided by (Responsible Party):
David B. Arciniegas, MD, Baylor College of Medicine

Brief Summary:

This is a four-site, randomized, parallel design, double-blind, placebo-controlled, 10-week trial of donepezil 10 mg daily for verbal memory problems among adults with TBI in the subacute or chronic recovery period. The study will recruit 160 persons with TBI and functionally important memory problems during a four-year period of open recruitment.

The study aims are:

  1. To evaluate the effects of treatment with donepezil on verbal memory as assessed by the Hopkins Verbal Learning Test-Revised Total Trial 1-3;
  2. To evaluate the effects of treatment with donepezil on memory-related activities as measured by the Everyday Memory Questionnaire;
  3. To evaluate the effects of donepezil on attention, processing speed, neuropsychiatric symptoms, community participation, quality of life, and caregiver experiences.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Memory Deficits Drug: Donepezil Drug: Placebo Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Four-site, Randomized, Parallel Design, Double-blind, Placebo-controlled, 10-week Trial of Donepezil 10 mg Daily for Verbal Memory Problems Among Adults With TBI in the Subacute or Chronic Recovery Period
Actual Study Start Date : October 1, 2013
Actual Primary Completion Date : September 30, 2018
Estimated Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory

Arm Intervention/treatment
Active Comparator: Donepezil
Donepezil 5 mg capsules daily for 14 days. Donepezil 10 mg capsules daily for 56 days.
Drug: Donepezil
Donepezil 5 mg capsule daily for 14 days. Donepezil 10 mg capsule daily for 56 days.
Other Names:
  • Donepezil hydrochloride
  • Aricept

Placebo Comparator: Placebo
Placebo capsules once daily for 70 days.
Drug: Placebo
Placebo capsule once daily for 70 days.




Primary Outcome Measures :
  1. Hopkins Verbal Learning Test-Revised (HVLT-R) Total Trials 1-3 [ Time Frame: study week 10 ]
    The effects of study treatment (donepezil or placebo) on persistent verbal memory impairments among persons with traumatic brain injury will be assessed by performance on HVLT-R Total Trials 1-3 at study week 10.


Secondary Outcome Measures :
  1. Cognitive Measures [ Time Frame: study week 10 ]
    The effects of study treatment (donepezil or placebo) on attention, processing speed, and executive function among persons with persistent verbal memory impairments following TBI will be assessed using the Trail Making Test - Parts A and B; the Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span, Symbol Search, Coding, Letter-Number Sequencing, and Processing Speed Index; and Controlled Oral Word Association Test at study week 10.

  2. Neuropsychiatric Measures [ Time Frame: study week 10 ]
    The effects of study treatment (donepezil or placebo) on neuropsychiatric symptoms among persons with persistent verbal memory impairments following TBI will be assessed by Brief Symptom Inventory 18 (BSI 18) - Global Severity Index and the Neuropsychiatric Inventory-Clinician version (NPI-C) Total and Domain scores at study week 10.

  3. Functional Measures [ Time Frame: study week 10 ]
    The effects of study treatment (donepezil or placebo) on functional status among persons with persistent verbal memory impairments will be assessed using participant and caregiver responses to the Everyday Memory Questionnaire, Participation Assessment with Recombined Tools-Objective, and Satisfaction with Life Scale scores at study week 10.

  4. Caregiver Measures [ Time Frame: study week 10 ]
    The effects of study treatment (donepezil or placebo) on distress among caregivers of persons with persistent verbal memory impairments will be assessed by the Caregiver Appraisal Scale - Perceived Burden Subscale as well as the NPI-C Caregiver Distress Scale scores at study week 10.

  5. Physical Measures [ Time Frame: study week 0, 6, and 10 ]
    The frequencies of adverse events associated with study treatment (donepezil or placebo) at study week 0, 6, and 10 will be assessed using the Side Effect Checklist.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Man or woman of any race, color, ethnicity, or national origin
  • 18-60 years old
  • Primary language English
  • Clinical diagnosis of traumatic brain injury using National Institute of Neurological Disorders and Stroke TBI Common Data Elements definition and merit assignment of International Classification of Disease (ICD9) codes 850.0-850.9, 851.0, 851.2, 852.0, 852.2, 852.4, 853.0, or 854.0
  • TBI is non-penetrating
  • TBI is of complicated mild or greater severity
  • TBI occurred at least 6 months prior to study participation
  • Persistent posttraumatic memory impairment, as defined by HVLT-R Total Trials 1-3 (Form 3) impairment ≥ 25% for Wechsler Test of Adult Reading-based intelligence quotient-adjusted performance expectations
  • Memory impairments are functionally significant, as defined by subject and/or caregiver endorsement of at least 3 memory problems, occurring at least weekly, on the Everyday Memory Questionnaire
  • Stable doses of allowed centrally-acting medications for at least 3 months prior to study participation, and participant and caregiver commitment not to alter doses of allowed medications during study
  • Capable of providing independent informed consent for study participation or provision of consent for study participation by a legally-authorized representative is supported by subject assent to study participation
  • A knowledgeable informant is available and willing to attend study visits or to provide required information by telephone interview on the day of study visits

Exclusion Criteria:

  • Pre-injury neurological and/or neurocognitive disorder
  • Primary diagnosis of hypoxic-ischemic brain injury or clinically definite post-TBI hypoxic-ischemic event (i.e., respiratory arrest and/or cardiac arrest) or non-TBI-related stroke
  • Pre- or post-injury psychotic and/or bipolar disorders
  • Post-injury substance use disorder (i.e., abuse or dependence diagnoses)
  • Clinically significant abnormalities on screening laboratory studies
  • Beck Depression Inventory-II (BDI-II) score ≥ 20 or BDI-II item 9 > 0
  • Brief Symptom Inventory 18 (BSI 18) Depression Subscale T score or Anxiety Subscale T score ≥ 63
  • Penetrating brain injury or cerebral lobectomy
  • Hearing, vision, and/or communication impairments that invalidate neuropsychological or other study assessments
  • Test of Memory Malingering Trial 2 score < 45
  • Use of an excluded medication in the month prior to study participation, known allergy to donepezil, or documented intolerance to donepezil
  • Posttraumatic epilepsy
  • Symptomatic bradycardia, cardiac conduction abnormality (i.e., first- or Type I second-degree atrioventricular blockade), atrial fibrillation, or unstable cardiovascular disease, including myocardial infarction within three months prior to study participation
  • Active, severe, or unstable pulmonary condition, including severe asthma
  • Signs or symptoms of gastrointestinal bleeding or active peptic ulcer disease within three months prior to study participation
  • Serum human chorionic gonadotropin (HCG)-confirmed pregnancy
  • For female participants, unable/unwilling to use barrier contraception during study participation, intrauterine device, or other implantable contraceptive method, unable/unwilling to forego breastfeeding infants or children during study participation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02255799


Locations
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United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Spaulding Rehabilitation Hospital
Charlestown, Massachusetts, United States, 02129
United States, Pennsylvania
Moss Rehabilitation Research Institute
Elkins Park, Pennsylvania, United States, 19027
United States, Texas
TIRR Memorial Hermann
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Spaulding Rehabilitation Hospital
Albert Einstein Healthcare Network
Indiana University
Craig Hospital
TIRR Memorial Hermann
Investigators
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Study Director: David Arciniegas, MD TIRR Memorial Hermann/Baylor College of Medicine
Principal Investigator: Angelle Sander, PhD TIRR Memorial Hermann/Baylor College of Medicine
Principal Investigator: Joseph Giacino, PhD Spaulding Rehabilitation Hospital
Principal Investigator: Tessa Hart, PhD Moss Rehabilitation Research Institute
Principal Investigator: Flora Hammond, MD Indiana University
Principal Investigator: Mark S Sherer, PhD TIRR Memorial Hermann

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Responsible Party: David B. Arciniegas, MD, Senior Scientist, Brain Injury Research Center, TIRR Memorial Hermann; Clinical Professor of Psychiatry, Baylor College of Medicine, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02255799     History of Changes
Other Study ID Numbers: H-33646 MEMRI-TBI-D Study
H133A130047 ( Other Grant/Funding Number: National Institute on Disability Rehabilitation and Research )
First Posted: October 3, 2014    Key Record Dates
Last Update Posted: December 28, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by David B. Arciniegas, MD, Baylor College of Medicine:
traumatic brain injury
TBI
brain injury
memory
verbal memory deficits
memory problems
cognition
cognitive impairment
neuropsychiatric symptoms
donepezil
acetylcholinesterase inhibitor

Additional relevant MeSH terms:
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Brain Injuries, Traumatic
Brain Injuries
Memory Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents