Randomized Controlled Trial of Galantamine, Methylphenidate, and Placebo for the Treatment of Cognitive Symptoms in Patients With Traumatic Brain Injury (TBI) and/or Posttraumatic Stress Disorder (PTSD)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 32
- 试验地点
- 7
- 主要终点
- Ruff Neurobehavioral Inventory - Postmorbid Cognitive Scale
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
- •Prior use of any other psychotropic medication that fails to meet the washout criterion of 2 weeks
- •Concurrent cognitive therapy, that will not be discontinued at least 7 days prior to the baseline visit
- •Baseline ECG and/or bloodwork reveals serious illness that precludes participation or use of study medications
- •Any procedure requiring general anesthesia
- •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.
- •Current (or past 2-week) use of alpha 2 adrenergic agonists such as guanfacine
研究组 & 干预措施
Sugar Pill
干预措施: Placebo Capsule (Drug)
Galantamine
干预措施: Galantamine 12 mg (Drug)
Methylphenidate
干预措施: Methylphenidate Hydrochloride 20 mg (Drug)
结局指标
主要结局
Ruff Neurobehavioral Inventory - Postmorbid Cognitive Scale
时间窗: Baseline through Week 12
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.
次要结局
- 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)