Effects of Acthar on Recovery From Cognitive Relapses in MS

April 1, 2020 updated by: Ralph H.B. Benedict, State University of New York at Buffalo

Effects of Adrenocorticotropic Hormone (ACTHAR Gel) on Recovery From Cognitive Relapses in Multiple Sclerosis

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14203
        • University at Buffalo-State University of New York, Department of Neurology, Buffalo General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day 0 and Day 90
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.
Day 0 and Day 90
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.
Day 0 and Day 90
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.
Day 0 and Day 90
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.
Day 0 and Day 90

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day 0 and Day 90
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.
Day 0 and Day 90
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.
Day 0 and Day 90
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.
Day 0 and Day 90

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events
Time Frame: Up to 3 months
The number of patients reporting adverse events over the course of the study
Up to 3 months
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.
Up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

State University of New York at Buffalo

Investigators

  • Principal Investigator: Ralph HB Benedict, PhD, University of Buffalo-State University of New York

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2013

Primary Completion (Actual)

November 1, 2018

Study Completion (Actual)

November 1, 2018

Study Registration Dates

First Submitted

October 23, 2014

First Submitted That Met QC Criteria

November 10, 2014

First Posted (Estimate)

November 14, 2014

Study Record Updates

Last Update Posted (Actual)

April 6, 2020

Last Update Submitted That Met QC Criteria

April 1, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 465028

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Sclerosis

Clinical Trials on Adrenocorticotropic Hormone

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guatemala

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe