Cognitive REmediation After Trauma Exposure Trial = CREATE Trial

NCT01416948 | Terminated Phase 2 DMC

• 1 other identifier: INTRuST-CREATE
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 7

Brief Summary

This study will evaluate the efficacy of methylphenidate and galantamine in the treatment of persistent cognitive symptoms associated with posttraumatic stress disorder (PTSD) and/or traumatic brain injury (TBI).

Conditions

Posttraumatic Stress Disorder; Traumatic Brain Injury

Keywords

Cognitive Complaints, TBI, PTSD

Outcome Measures

Primary Outcomes (1)

• Ruff Neurobehavioral Inventory - Postmorbid Cognitive Scale

  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.

  Baseline through Week 12

Secondary Outcomes (5)

• Rivermead Postconcussion Symptom Questionnaire (RPCSQ)

  Baseline through week 12

• Patient Health Questionnaire-9 (PHQ - 9)

  Baseline through week 12

• PTSD Checklist - Specific Event Version (PCL-S)

  Baseline through week 12

• PreMorbid-Postmorbid Difference Score on Cognitive Scale of Ruff Neurobehavioral Inventory

  Baseline through 12 weeks

• Neuropsychological Tests of Memory, Attention and Other Executive Functions

  Baseline through 12 weeks

Study Arms (3)

Sugar Pill

PLACEBO COMPARATOR

Drug: Placebo Capsule

Galantamine

ACTIVE COMPARATOR

Drug: Galantamine 12 mg

Methylphenidate

EXPERIMENTAL

Drug: Methylphenidate Hydrochloride 20 mg

Interventions

Methylphenidate Hydrochloride 20 mg DRUG

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.

Also known as: Ritalin

Methylphenidate

Placebo Capsule DRUG

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.

Sugar Pill

Galantamine 12 mg DRUG

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.

Also known as: Razadyne

Galantamine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-55 years
• Has a DSM-IV diagnosis of chronic (≥ 3 months duration) PTSD and/or a history of TBI (≥ 3 months duration) as established by the INTRuST standard TBI Screening questionnaire.
• TBI must have occurred ≥ 90 days prior to the screening visit
• With either diagnosis (i.e., PTSD or TBI), the subject must have clinically significant cognitive complaints, as indicated by a T score ≥ 60 on the postmorbid Cognitive scale of the RNBI
• Interested in receiving treatment for cognitive symptoms
• Capable of giving informed consent

You may not qualify if:

• Known sensitivity, or previous adverse reaction(s), to GAL or other acetylcholinesterase inhibitors such as donepezil or rivastigmine OR Known sensitivity or previous adverse reactions to MPH or other stimulant medications (e.g., dextroamphetamine, long-acting methylphenidate preparations)
• Pregnant, likely to become pregnant, or lactating (female subjects only)
• Does not speak English
• WRAT scaled score \< 70
• History of glaucoma
• History of cardiac conditions (e.g., bradycardia, AV block) or history of taking medications that are associated with conduction abnormalities
• History of seizure disorder (including post-traumatic epilepsy), neurosurgery, or neurodisability \[Note that history of "impact seizure" is permitted\]
• Lifetime history of psychotic disorder, Bipolar I, stimulant abuse or dependence, or tic disorder
• Alcohol dependence, alcohol abuse\*, substance abuse, or substance dependence in the past 6 months \[\*Alcohol abuse will be defined as MINI diagnosis of "Alcohol Abuse" AND an AUDIT-C score of ≥ 5; Dawson, Grant, \& Stinson, 2005\].
• Current active suicidal ideation, or history of actual attempt within the past 10 years
• Current severe depressive symptoms, as indicated by a score of 20 or higher on the PHQ-9
• Current (or past 2-week) use of monoamine oxidase inhibitors \[Washout period of at least 2 weeks is required\]
• Current (or past 2-week) use of medications that potentiate cholinergic function (i.e., other cholinesterase inhibitors or procholinergic agents), or use of over-the-counter procholinergics \[Washout period of at least 2 weeks is required\]
• Current (or past 2-week) use of amphetamine-type stimulants or modafinil
• Current use of any other psychotropic medication that fails to meet the stabilization criterion of a minimum of 4 weeks on the same medication(s) and dose(s)

Sponsors & Collaborators

• INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium: lead
• U.S. Army Medical Research and Development Command: collaborator

Study Sites (7)

VA San Diego Healthcare System

San Diego, California, 92161, United States

Location

Spaulding Rehabilitation Hospital

Boston, Massachusetts, 02114, United States

Location

Manchester VA Medical Center

Manchester, New Hampshire, 03104, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Ralph H. Johnson VA Medical Center

Charleston, South Carolina, 29401, United States

Location

White River Junction VA Medical Center

White River Junction, Vermont, 05009, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Brain Injuries, Traumatic

Interventions

Methylphenidate; Galantamine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amaryllidaceae Alkaloids; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Thomas W McAllister, M.D.

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• Ross Zafonte, M.D.

  Spaulding Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2011
• First Posted: August 15, 2011
• Study Start: August 1, 2011
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: April 26, 2013

Record last verified: 2013-04

Locations

US (7)