Multicenter Evaluation of Memory Remediation After TBI With Donepezil

• Status: Active, not recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Albert Einstein Healthcare Network; Craig Hospital; Indiana University; Spaulding Rehabilitation Hospital; TIRR Memorial Hermann
• Treatments: Donepezil

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