Effects of Acthar on Recovery From Cognitive Relapses in MS
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|ClinicalTrials.gov Identifier: NCT02290444|
Recruitment Status : Completed
First Posted : November 14, 2014
Results First Posted : April 6, 2020
Last Update Posted : April 6, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis||Drug: Adrenocorticotropic Hormone||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||64 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Supportive Care|
|Official Title:||Effects of Adrenocorticotropic Hormone (ACTHAR Gel) on Recovery From Cognitive Relapses in Multiple Sclerosis|
|Study Start Date :||August 2013|
|Actual Primary Completion Date :||November 1, 2018|
|Actual Study Completion Date :||November 1, 2018|
Experimental: 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.
Drug: Adrenocorticotropic Hormone
Acthar Gel will be administered in accordance with the recommendations set forth in the package insert. The dosage may be individualized according to the medical condition of each patient. Frequency and dose of the drug may be determined by considering the severity of the disease and the initial response of the patient.
Other Name: Acthar gel
No Intervention: Stable Multiple Sclerosis Patients
Individuals whose Multiple Sclerosis is currently in a stable state (not currently or recently exacerbating) are age-matched with relapsing MS patients. There is no intervention for individuals with MS whose are currently in a stable state.
- Change From Baseline on the Symbol Digit Modalities Test (SDMT) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
- Change From Baseline on the Expanded Disability Status Scale (EDSS). [ Time Frame: Day 0 and Day 90 ]A clinician assigned measure of disability specific to MS. Minimum of 0 (no disability), maximum of 10 (death due to MS). Higher scores indicate greater disability. The difference in total score on the EDSS from Day 0 to Day 90 were analyzed to address change in this outcome.
- Change From Baseline on the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) [ Time Frame: Day 0 and Day 90 ]A self and informant rating measure of perceived cognitive problems. Minimum of 0, maximum of 60. Higher scores indicates greater self-reported neuropsychological impairment. The difference in total score on the MSNQ from Day 0 to Day 90 were analyzed to address change in this outcome.
- Change From Baseline on the Beck Depression Inventory-Fast Screen (BDI-FS) [ Time Frame: Day 0 and Day 90 ]A self-report, multiple choice inventory of depression. Minimum of 0, maximum of 21. Higher score indicates higher levels of depression. The difference in total score on the BDI-FS from Day 0 to Day 90 were analyzed to address change in this outcome.
- Change From Baseline on the Fatigue Severity Scale (FSS) [ Time Frame: Day 0 and Day 90 ]A self-report measure of fatigue. 1 (no fatigue) to 9 (severe fatigue). The difference in total score on FSS from Day 0 to Day 90 were analyzed to address change in this outcome.
- Incidence of Adverse Events [ Time Frame: Up to 3 months ]The number of patients reporting adverse events over the course of the study
- Change From Baseline in Concurrent Medications [ Time Frame: Up to 3 months ]Initiation or discontinuation of any medications occurring over the course of the study; monitored by clinician and study personnel.
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|Ages Eligible for Study:||18 Years to 65 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 ≤ 7.0.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02290444
|United States, New York|
|University at Buffalo-State University of New York, Department of Neurology, Buffalo General Hospital|
|Buffalo, New York, United States, 14203|
|Principal Investigator:||Ralph HB Benedict, PhD||University of Buffalo-State University of New York|
Documents provided by Ralph H.B. Benedict, State University of New York at Buffalo:
|Responsible Party:||Ralph H.B. Benedict, Professor of Neurology and Psychiatry, State University of New York at Buffalo|
|Other Study ID Numbers:||
|First Posted:||November 14, 2014 Key Record Dates|
|Results First Posted:||April 6, 2020|
|Last Update Posted:||April 6, 2020|
|Last Verified:||April 2020|
Acute Relapsing Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Immune System Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action