Cognitive REmediation After Trauma Exposure Trial = CREATE Trial

INTRuST, Post-Traumatic Stress Disorder - Traumatic Brain Injury Clinical Consortium

Status and phase: Terminated; Phase 2

Conditions: Posttraumatic Stress Disorder; Traumatic Brain Injury

Treatments: Drug: Placebo Capsule; Drug: Methylphenidate Hydrochloride 20 mg; Drug: Galantamine 12 mg

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT01416948

INTRuST-CREATE

Details and patient eligibility

About

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).

Full description

Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are prevalent in service members returning from Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND). Virtually all individuals who suffer TBI (TBI) have acute cognitive effects, and a significant number have persistent symptoms. A large number of individuals with PTSD also report problems with cognition, however, little is known about the treatment of cognitive complaints in either condition and less is known about cognitive complaints in individuals with co-occurring TBI and PTSD.

There is some preclinical evidence that both the cholinergic and catecholaminergic neurotransmitter systems play important roles in cognitive function in healthy individuals as well as those with mTBI and/or PTSD. We propose to evaluate the efficacy of two pharmacotherapies, one that predominantly augments cholinergic function (galantamine [GAL]) and one that augments predominantly catecholaminergic function (methylphenidate [MPH]), for reducing cognitive symptoms in individuals with TBI and/or PTSD.

Using a double-blind, randomized, placebo controlled design, 159 individuals with TBI and/or PTSD with persistent cognitive complaints will be randomized to receive galantamine 12 mg BID, methylphenidate 20 mg BID, or placebo for 12 weeks. The primary objective is to assess the efficacy of galantamine and methylphenidate in reducing cognitive complaints in patients with PTSD and/or TBI. Secondary objectives are to assess the extent to which non-cognitive distress responds to galantamine or methylphenidate, and assess the effect that galantamine and methylphenidate have on cognitive performance.

Enrollment: 32 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 18-55 years
2. 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.
3. TBI must have occurred ≥ 90 days prior to the screening visit
4. 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
5. Interested in receiving treatment for cognitive symptoms
6. Capable of giving informed consent

Exclusion criteria

1. 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)
2. Pregnant, likely to become pregnant, or lactating (female subjects only)
3. Does not speak English
4. WRAT scaled score < 70
5. History of glaucoma
6. History of cardiac conditions (e.g., bradycardia, AV block) or history of taking medications that are associated with conduction abnormalities
7. History of seizure disorder (including post-traumatic epilepsy), neurosurgery, or neurodisability [Note that history of "impact seizure" is permitted]
8. Lifetime history of psychotic disorder, Bipolar I, stimulant abuse or dependence, or tic disorder
9. 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].
10. Current active suicidal ideation, or history of actual attempt within the past 10 years
11. Current severe depressive symptoms, as indicated by a score of 20 or higher on the PHQ-9
12. Current (or past 2-week) use of monoamine oxidase inhibitors [Washout period of at least 2 weeks is required]
13. 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]
14. Current (or past 2-week) use of amphetamine-type stimulants or modafinil
15. 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)
16. Prior use of any other psychotropic medication that fails to meet the washout criterion of 2 weeks
17. Concurrent cognitive therapy, that will not be discontinued at least 7 days prior to the baseline visit
18. Baseline ECG and/or bloodwork reveals serious illness that precludes participation or use of study medications
19. Any procedure requiring general anesthesia
20. History of peptic ulcer disease or GI bleed or endoscopic procedure for GERD within the last year. Subjects taking physician prescribed treatment for GERD will be allowed to participate at the discretion of the PI after discussion with the primary treating physician.
21. Current (or past 2-week) use of alpha 2 adrenergic agonists such as guanfacine

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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32 participants in 3 patient groups, including a placebo group

Sugar Pill

Placebo Comparator group

Treatment:

Drug: Placebo Capsule

Galantamine

Active Comparator group

Treatment:

Drug: Galantamine 12 mg

Methylphenidate

Experimental group

Treatment:

Drug: Methylphenidate Hydrochloride 20 mg