Multicenter Evaluation of Memory Remediation After TBI With Donepezil

NCT02255799 | Completed Phase 3 DMC

• 2 other identifiers: H-33646 MEMRI-TBI-D StudyH133A130047
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 4

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. 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. 2.To evaluate the effects of treatment with donepezil on memory-related activities as measured by the Everyday Memory Questionnaire;
3. 3.To evaluate the effects of donepezil on attention, processing speed, neuropsychiatric symptoms, community participation, quality of life, and caregiver experiences.

Conditions

Traumatic Brain Injury; Memory Deficits

Keywords

traumatic brain injury; TBI; brain injury; memory; verbal memory deficits; memory problems; cognition; cognitive impairment; neuropsychiatric symptoms; donepezil; acetylcholinesterase inhibitor

Outcome Measures

Primary Outcomes (1)

• Hopkins Verbal Learning Test-Revised (HVLT-R) Total Trials 1-3

  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.

  study week 10

Secondary Outcomes (5)

• Cognitive Measures

  study week 10

• Neuropsychiatric Measures

  study week 10

• Functional Measures

  study week 10

• Caregiver Measures

  study week 10

• Physical Measures

  study week 0, 6, and 10

Study Arms (2)

Donepezil

ACTIVE COMPARATOR

Donepezil 5 mg capsules daily for 14 days. Donepezil 10 mg capsules daily for 56 days.

Drug: Donepezil

Placebo

PLACEBO COMPARATOR

Placebo capsules once daily for 70 days.

Drug: Placebo

Interventions

Donepezil DRUG

Donepezil 5 mg capsule daily for 14 days. Donepezil 10 mg capsule daily for 56 days.

Also known as: Donepezil hydrochloride, Aricept

Donepezil

Placebo DRUG

Placebo capsule once daily for 70 days.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Man or woman of any race, color, ethnicity, or national origin
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Spaulding Rehabilitation Hospital: collaborator
• Albert Einstein Healthcare Network: collaborator
• Indiana University: collaborator
• Craig Hospital: collaborator
• TIRR Memorial Hermann: collaborator

Study Sites (4)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Spaulding Rehabilitation Hospital

Charlestown, Massachusetts, 02129, United States

Location

Moss Rehabilitation Research Institute

Elkins Park, Pennsylvania, 19027, United States

Location

TIRR Memorial Hermann

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Memory Disorders; Brain Injuries; Cognitive Dysfunction

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• David Arciniegas, MD

  TIRR Memorial Hermann/Baylor College of Medicine

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants received donepezil 5 mg daily or matching placebo for 2 weeks followed by donepezil 10 mg daily or matching placebo for 8 weeks; after the 10-week treatment period, treatment was discontinued, and patients were observed for an additional 4 weeks. Participants and all study personnel (except the individual responsible for generation of the randomization code) were unaware of treatment allocation throughout the study. Site investigators attested to the integrity of allocation concealment at the conclusion of the study's treatment phase. For additional details on these and related study drug, randomization, blinding, and allocation concealment methods, see section 12 in part A of the online supplement at https://psychiatryonline.org/doi/10.1176/appi.neuropsych.20230055.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist, Brain Injury Research Center, TIRR Memorial Hermann; Clinical Professor of Psychiatry, Baylor College of Medicine

Model Details: Prospective, multisite, randomized, parallel-group design, double-blind, placebo-controlled, 10-week clinical trial.

Study Record Dates

• First Submitted: September 25, 2014
• First Posted: October 3, 2014
• Study Start: September 1, 2013
• Primary Completion: December 4, 2024
• Study Completion: December 4, 2024
• Last Updated: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)