Effects of Adrenocorticotropic Hormone (ACTHAR Gel) on Recovery From Cognitive Relapses in Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Change From Baseline on the Symbol Digit Modalities Test (SDMT)
研究概览
简要总结
The purpose of this study is to evaluate the effect of a medication called Acthar on recovery from multiple sclerosis-related relapses that impact cognition.
详细描述
This is a prospective, open-label study of Acthar administered as treatment for an acute cognitive relapse. Primary and secondary endpoints will be collected prior to Acthar administration and at 3-month follow-up. Comparison will be made to a stable MS control group.
The objectives of the study are:
- To replicate prior findings with steroid therapy for MS patients for cognitive relapses, using instead Acthar Gel as the treating agent. The investigators will determine if the decrease on cognitive endpoints at the time of relapse exceeds that of stable MS controls.
- To compare the effects above to a previously acquired dataset of relapsing patients treated with steroids. This is a quasi-experimental design in so far as the steroid treated group data were previously acquired in a separate study.
The primary hypothesis of the study is that, due to the enhanced melanocortin response in Acthar the recovery from cognitive changes occurring during cognitively focused relapse will be significant compared to stable MS patients matched on age, time since testing, and cognitive performance on the SDMT.
Target enrollment for the Acthar treatment group will be 30 MS patients under care at the Jacobs Neurological Institute with existing neuropsychological baseline in the past four years in whom a cognitive relapse or new supratentorial GAD enhancing lesion(s) on MRI have been identified. Cognitive relapse will be identified based on clinical presentation of acute worsening of cognitive symptoms in the domains of processing speed, concentration, episodic memory, working memory, and/or fatigue. Patients whose clinical MRI indicate new active GAD enhancing lesions will be screened for the presence of self-perceived cognitive decline, without new physical symptoms. Thirty (30) clinically stable MS patients matched on age, time since testing, and cognitive performance on the SDMT will be recruited from the pool of patients with existing cognitive baselines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males/Females between 18 and 65 years of age who are capable of understanding and complying with the protocol (ie. have completed at least a 9th grade education and are fluent English).
- •Have a diagnosis of Relapsing Remitting MS (RRMS) or early Secondary Progressive MS (SPMS) as per revised McDonald's Criteria.
- •Have an Expanded Disability Severity Scale (EDSS) of ≤ 7.
- •Have had valid neuropsychological testing (NP) within the past 4 years
- •Experiencing an acute cognitive relapse identified by a clinical care provider as a.) a cognitive symptom of recent origin developing over 48 hours, or b.) supratentorial GAD enhancing lesions on MRI with confirmed cognitive decline.
- •Confirmation of cognitive decline will be obtained by administering the Symbol Digit Modalities Test (SDMT) as a screening procedure for the study and comparing it to scores obtained within 4 years (see inclusion criteria #4). Participants qualify if a raw point change on the SDMT greater than or equal to -3 points is detected.
- •Are capable of performing the requirements of neuropsychological (NP) testing, including near visual acuity 20/70 or better with correction.
- •Have given written informed consent prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his/her future medical care.
排除标准
- •Are found to have evidence on MRI of new lesions in the brainstem, spinal cord, or optic nerve.
- •Have clear new physical signs or symptoms that are referable to the cord, brainstem or optic nerve.
- •Have cognitive deficits/impairment caused by concomitant medication usage, or are attributable to another medical condition or significant neurological/psychological disease.
- •Have evidence of current major depression as determined by a positive Beck Depression Inventory-Fast Screen (BDI-FS) and clinician interview.
- •Patients with changes to medications known to influence cognition (narcotics, stimulants, etc.) or disease modifying therapy within one month of study initiation (or within a time frame deemed high risk by treating physician) will be excluded.
- •Are taking any medication, or have any medical condition contraindicated with Acthar.
- •Presence of current infections as determined by clinician interview.
- •Are currently nursing, intentionally seeking pregnancy, or deemed at-risk for unplanned pregnancy.
研究组 & 干预措施
Cognitively Relapsing Patients
For individuals experiencing cognitive relapses/exacerbations, 5ml/80 IU of Adrenocorticotropic Hormone will be administered through either subcutaneous or intramuscular self-injection (selected by the patient) for 5-days.
干预措施: Adrenocorticotropic Hormone (Drug)
结局指标
主要结局
Change From Baseline on the Symbol Digit Modalities Test (SDMT)
时间窗: Day 0 and Day 90
A measure of visual processing speed and working memory. Minimum score of 0, Maximum score of 120. Higher scores indicate better performance. The difference in total correct responses on the SDMT from Day 0 to Day 90 were analyzed to address change in this outcome.
Timed 25-foot Walk
时间窗: Day 0 and Day 90
An MS-specific measure of functional status walking speed. How many seconds does it take to walk 25 feet. Ceiling value of 300 seconds.
Change From Baseline on the Paced Auditory Serial Addition Test (PASAT)
时间窗: Day 0 and Day 90
A measure of auditory processing speed and working memory. Minimum value of 0, maximum value of 60. Higher score indicates better performance. The difference in total correct on the PASAT from Day 0 to Day 90 were analyzed to address change in this outcome.
Change From Baseline on the Brief Visuospatial Memory Test-Revised (BVMT-R)
时间窗: Day 0 and Day 90
A measure of visual/spatial memory. Minimum of 0, maximum of 36. Higher score indicates better performance. The difference in total learning score on the BVMT-R from Day 0 to Day 90 were analyzed to address change in this outcome.
Change From Baseline on the California Verbal Learning Test, Second Edition (CVLT-II)
时间窗: Day 0 and Day 90
A measure of auditory/verbal episodic memory. Minimum of 0, maximum of 80. Higher score indicates better performance. The difference in total learning score on the CVLT-II from Day 0 to Day 90 were analyzed to address change in this outcome.
次要结局
- Change From Baseline on the Expanded Disability Status Scale (EDSS).(Day 0 and Day 90)
- Change From Baseline on the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)(Day 0 and Day 90)
- Change From Baseline on the Beck Depression Inventory-Fast Screen (BDI-FS)(Day 0 and Day 90)
- Change From Baseline on the Fatigue Severity Scale (FSS)(Day 0 and Day 90)
研究者
Ralph H.B. Benedict
Professor of Neurology and Psychiatry
State University of New York at Buffalo