Methylphenidate (Ritalin) and Memory/Attention in Traumatic Brain Injury (TBI)

NCT00453921 | Completed Results DMC

• 2 other identifiers: 173635R01HD047242
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 3

Brief Summary

Traumatic brain injury (TBI) is a significant public health problem, with 1.5-2.0 million Americans injured each year. Cognitive deficits, particularly in the domains of memory and attention are frequently the source of lingering disability after TBI and a source of enormous distress to the injured individuals and their family/caregivers. To date, interventions to ameliorate chronic cognitive deficits have been directed at either pharmacological interventions or cognitive rehabilitation. We propose to (1) To compare the efficacy of three interventions: memory and attention training (MAAT), methylphenidate, and memory/attention training in combination with methylphenidate and (2) use functional MRI (fMRI) to characterize changes in activation of the neural circuitry of memory and attention due to MAAT alone, methylphenidate alone, and MAAT in combination with methylphenidate. This is a two by two design with medication (methylphenidate/placebo) and cognitive therapy (Memory and Attention Training (MAAT) or an Attention control intervention) as possible interventions. Using a randomized, placebo-controlled, double-blind design, 200 individuals with persistent cognitive deficits 6-12 months after MTBI will be randomized to receive a six week trial of either (1) MAAT and placebo, (2) MAAT and methylphenidate (0.3 mg/kg BID), (3) attention control intervention and methylphenidate (0.3 mg/kg BID), or (4) attention control intervention and placebo. Symptom distress, attention and memory performance, and activation patterns of the neural circuitry of attention and memory while undergoing fMRI will be characterized at baseline, and after the four treatment conditions. This study will provide important information on three interventions for the most disabling sequelae of an enormous public health problem. Further, it will help to clarify underlying neural mechanisms and suggest additional treatment possibilities.

Conditions

Brain Injury

Keywords

TBI; Memory; Methylphenidate; Ritalin; Memory and Attention Training

Outcome Measures

Primary Outcomes (6)

• Neuropsychological Assessment, CVLT-II

  Memory measure: California Verbal Learning Test, 2nd edition (CVLT), Total, trials 1-5 (range: 0-80). Higher scores are better outcome.

  post-intervention (at least 7 weeks)

• Neuropsychological Assessment - CPT, Distractibility Condition (Reaction Time)

  Continuous Performance Test, Distractibility Condition (Reaction Time in msecs) (range: 0-800). Higher score is worse performance.

  post-intervention (at least 7 weeks)

• Functional MRI Task Performance and Brain Activation (Change From Baseline to Post-treatment)

  Change in performance (percent correct,adjusted for guessing) from pre-(baseline) to post-treatment (approximately 7 weeks) for in-scanner n-back working memory task (Range: 0-100). Higher scores means better performance.

  pre- to post-6 week treatment intervention (at least 7 weeks)

• Change in Anterior Cingulate Gyrus Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention

  Change from pre- to post-treatment in brain activation in the anterior cingulate region of interest in arbitrary units provided by the SPM (statistical parametric mapping) program (range: unknown). Higher scores indicate greater increase in activation from pre- to post-treatment.

  pre- to post-intervention (at least 7 weeks)

• Change in Left Middle/Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention

  Change from pre- to post-treatment in brain activation in the left middle/inferior frontal region of interest in arbitrary units provided by the SPM (statistical parametric mapping) program (range: unknown). Higher scores indicate greater increase in activation from pre- to post-treatment.

  pre- to post-treatment (at least 7 weeks)

• Change in Right Inferior Frontal Activation During Working Memory Processing (3-back > 0-back Condition) From Baseline to Post-intervention

  Change from pre- to post-treatment in brain activation in the right inferior frontal region of interest in arbitrary units provided by the SPM (statistical parametric mapping) program (range: unknown). Higher scores indicate greater increase in activation from pre- to post-treatment.

  pre- to post-treatment (at least 7 weeks)

Secondary Outcomes (1)

• Self Report Questionnaire - MASQ

  post-intervention (at least 7 weeks)

Study Arms (4)

1

PLACEBO COMPARATOR

Placebo Capsule and Placebo Memory and Attention Training (Placebo as both conditions)

Other: Placebo as both treatments

2

ACTIVE COMPARATOR

Methylphenidate capsules and Memory and Attention Training (Active Med/Active therapy)

Drug: Methylphenidate; Behavioral: Memory and Attention Training

3

ACTIVE COMPARATOR

Methylphenidate capsules and Placebo Memory and Attention Training (Active Med/Placebo therapy)

Drug: Methylphenidate

4

ACTIVE COMPARATOR

Placebo capsules and Memory and Attention Training (Placebo Med/Active therapy)

Behavioral: Memory and Attention Training

Interventions

Methylphenidate DRUG

Dosage dependent on weight

2; 3

Memory and Attention Training BEHAVIORAL

Weekly Memory and Attention Training with at home practice.

2; 4

Placebo as both treatments OTHER

Placebo capsules and Placebo Memory and Attention Training

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Individuals aged 18-65 who sustained a mild to severe TBI 4 months prior to study entry.
• Cognitive Deficits: Subjects will have either subjective and objective evidence of persistent cognitive deficits. Subjects must report persistent memory or attention deficits as a result of their injury, which are of sufficient severity to interfere with social and/or occupational functioning. Subjects must either score more than 2 standard deviations below the age adjusted norm or estimates of baseline premorbid function on one or more tests of attention and/or memory administered as part of the baseline screening cognitive battery (see below), or score greater than 1.0 standard deviations below either age adjusted norms or estimates of premorbid function on 2 or more of the screening tests.

You may not qualify if:

• The following factors will exclude otherwise eligible subjects from participation:
• a history of other neurologic disorders (such as epilepsy, cerebrovascular disease, mental retardation, neurodegenerative disorders)
• significant systemic medical illness such as clinically significant liver disease, renal disease, atherosclerotic coronary vascular disease, or hypertension requiring medication management
• women currently pregnant or lactating. Female participants will be asked to take a pregnancy test to confirm they are not currently pregnant.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (3)

University of Colorado at Denver

Denver, Colorado, 80291-0238, United States

Location

Indiana University

Indianapolis, Indiana, 46266-6057, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03753, United States

Location

Related Publications (17)

• McAllister TW, Flashman LA, McDonald BC, Saykin AJ. Mechanisms of working memory dysfunction after mild and moderate TBI: evidence from functional MRI and neurogenetics. J Neurotrauma. 2006 Oct;23(10):1450-67. doi: 10.1089/neu.2006.23.1450.

  PMID: 17020482 BACKGROUND

• Neurobehavioral Guidelines Working Group; Warden DL, Gordon B, McAllister TW, Silver JM, Barth JT, Bruns J, Drake A, Gentry T, Jagoda A, Katz DI, Kraus J, Labbate LA, Ryan LM, Sparling MB, Walters B, Whyte J, Zapata A, Zitnay G. Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury. J Neurotrauma. 2006 Oct;23(10):1468-501. doi: 10.1089/neu.2006.23.1468.

  PMID: 17020483 BACKGROUND

• McAllister TW, Rhodes CH, Flashman LA, McDonald BC, Belloni D, Saykin AJ. Effect of the dopamine D2 receptor T allele on response latency after mild traumatic brain injury. Am J Psychiatry. 2005 Sep;162(9):1749-51. doi: 10.1176/appi.ajp.162.9.1749.

  PMID: 16135640 BACKGROUND

• McAllister TW, Flashman LA, Sparling MB, Saykin AJ. Working memory deficits after traumatic brain injury: catecholaminergic mechanisms and prospects for treatment -- a review. Brain Inj. 2004 Apr;18(4):331-50. doi: 10.1080/02699050310001617370.

  PMID: 14742148 BACKGROUND

• McAllister TW, Ferrell RB. Evaluation and treatment of psychosis after traumatic brain injury. NeuroRehabilitation. 2002;17(4):357-68.

  PMID: 12547983 BACKGROUND

• Flashman LA, McAllister TW. Lack of awareness and its impact in traumatic brain injury. NeuroRehabilitation. 2002;17(4):285-96.

  PMID: 12547977 BACKGROUND

• McAllister TW, Arciniegas D. Evaluation and treatment of postconcussive symptoms. NeuroRehabilitation. 2002;17(4):265-83.

  PMID: 12547976 BACKGROUND

• McAllister TW. Evaluation and treatment of neurobehavioral complications of traumatic brain injury--have we made any progress? NeuroRehabilitation. 2002;17(4):263-4. No abstract available.

  PMID: 12547975 BACKGROUND

• McAllister TW, Sparling MB, Flashman LA, Saykin AJ. Neuroimaging findings in mild traumatic brain injury. J Clin Exp Neuropsychol. 2001 Dec;23(6):775-91. doi: 10.1076/jcen.23.6.775.1026.

  PMID: 11910544 BACKGROUND

• McAllister TW, Sparling MB, Flashman LA, Guerin SJ, Mamourian AC, Saykin AJ. Differential working memory load effects after mild traumatic brain injury. Neuroimage. 2001 Nov;14(5):1004-12. doi: 10.1006/nimg.2001.0899.

  PMID: 11697932 BACKGROUND

• McAllister TW, Saykin AJ, Flashman LA, Sparling MB, Johnson SC, Guerin SJ, Mamourian AC, Weaver JB, Yanofsky N. Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study. Neurology. 1999 Oct 12;53(6):1300-8. doi: 10.1212/wnl.53.6.1300.

  PMID: 10522888 BACKGROUND

• McAllister TW. Traumatic Brain Injury and Psychosis: What Is the Connection? Semin Clin Neuropsychiatry. 1998 Jul;3(3):211-223.

  PMID: 10085209 BACKGROUND

• Flashman LA, Amador X, McAllister TW. Lack of Awareness of Deficits in Traumatic Brain Injury. Semin Clin Neuropsychiatry. 1998 Jul;3(3):201-210.

  PMID: 10085208 BACKGROUND

• McAllister TW, Green RL. Traumatic Brain Injury: A Model of Acquired Psychiatric Illness? Semin Clin Neuropsychiatry. 1998 Jul;3(3):158-159. No abstract available.

  PMID: 10085203 BACKGROUND

• McAllister TW. Evaluation of brain injury related behavioral disturbances in community mental health centers. Community Ment Health J. 1997 Aug;33(4):341-58; discussion 359-64. doi: 10.1023/a:1025055426260.

  PMID: 9250431 BACKGROUND

• Silver JM, McAllister TW. Forensic issues in the neuropsychiatric evaluation of the patient with mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 1997 Winter;9(1):102-13. doi: 10.1176/jnp.9.1.102. No abstract available.

  PMID: 9017537 BACKGROUND

• McAllister TW. Neuropsychiatric sequelae of head injuries. Psychiatr Clin North Am. 1992 Jun;15(2):395-413.

  PMID: 1603732 BACKGROUND

Related Links

• Brain Injury Association of New Hampshire
• Brain Injury Association of Vermont

MeSH Terms

Conditions

Brain Injuries

Interventions

Methylphenidate

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Laura Flashman
• Organization: Dartmouth Hitchcock Medical Center

Laura.A.Flashman@hitchcock.org

6036505824

Study Officials

• Thomas W McAllister, MD

  Dartmouth-Hitchcock Medical Center, Dartmouth Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: March 27, 2007
• First Posted: March 29, 2007
• Study Start: February 1, 2007
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 13, 2018
• Results First Posted: June 7, 2018

Record last verified: 2018-06

Locations

US (3)