Clinical trial NCT02290444: Effects of Acthar on Recovery From Cognitive Relapses in MS
Official title: Effects of Adrenocorticotropic Hormone (ACTHAR Gel) on Recovery From Cognitive Relapses in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Acute Relapsing Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Lead sponsor: State University of New York at Buffalo
Sponsor class: OTHER
First posted: 2014-11-14
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

Detailed description: 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:

1. 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.
2. 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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Have a diagnosis of Relapsing Remitting MS (RRMS) or early Secondary Progressive MS (SPMS) as per revised McDonald's Criteria.
3. Have an Expanded Disability Severity Scale (EDSS) of ≤ 7.0.
4. Have had valid neuropsychological testing (NP) within the past 4 years
5. 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.
6. Are capable of performing the requirements of neuropsychological (NP) testing, including near visual acuity 20/70 or better with correction.
7. 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.

Exclusion Criteria:

1. Are found to have evidence on MRI of new lesions in the brainstem, spinal cord, or optic nerve.
2. Have clear new physical signs or symptoms that are referable to the cord, brainstem or optic nerve.
3. Have cognitive deficits/impairment caused by concomitant medication usage, or are attributable to another medical condition or significant neurological/psychological disease.
4. Have evidence of current major depression as determined by a positive Beck Depression Inventory-Fast Screen (BDI-FS) and clinician interview.
5. 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.
6. Are taking any medication, or have any medical condition contraindicated with Acthar.
7. Presence of current infections as determined by clinician interview.
8. Are currently nursing, intentionally seeking pregnancy, or deemed at-risk for unplanned pregnancy.

Primary outcomes:
measure: Change From Baseline on the Symbol Digit Modalities Test (SDMT)
timeFrame: Day 0 and Day 90
measure: Timed 25-foot Walk
timeFrame: Day 0 and Day 90
measure: Change From Baseline on the Paced Auditory Serial Addition Test (PASAT)
timeFrame: Day 0 and Day 90
measure: Change From Baseline on the Brief Visuospatial Memory Test-Revised (BVMT-R)
timeFrame: Day 0 and Day 90
measure: Change From Baseline on the California Verbal Learning Test, Second Edition (CVLT-II)
timeFrame: Day 0 and Day 90
Secondary outcomes:
measure: Change From Baseline on the Expanded Disability Status Scale (EDSS).
timeFrame: Day 0 and Day 90
measure: Change From Baseline on the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)
timeFrame: Day 0 and Day 90
measure: Change From Baseline on the Beck Depression Inventory-Fast Screen (BDI-FS)
timeFrame: Day 0 and Day 90
measure: Change From Baseline on the Fatigue Severity Scale (FSS)
timeFrame: Day 0 and Day 90
Other outcomes:
measure: Incidence of Adverse Events
timeFrame: Up to 3 months
measure: Change From Baseline in Concurrent Medications
timeFrame: Up to 3 months
Locations:
city: Buffalo
country: United States
facility: University at Buffalo-State University of New York, Department of Neurology, Buffalo General Hospital
state: New York
Study officials:
affiliation: University of Buffalo-State University of New York
name: Ralph HB Benedict, PhD
role: PRINCIPAL_INVESTIGATOR
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