Multiple Sclerosis
Conditions
Keywords
Acute Relapsing Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive
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.
Interventions
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.
Sponsors
State University of New York at Buffalo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Brief Visuospatial Memory Test-Revised (BVMT-R) | 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 Symbol Digit Modalities Test (SDMT) | 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 | 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) | 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 California Verbal Learning Test, Second Edition (CVLT-II) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline on the Fatigue Severity Scale (FSS) | 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. |
| Change From Baseline on the Expanded Disability Status Scale (EDSS). | 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) | 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) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | Up to 3 months | The number of patients reporting adverse events over the course of the study |
| Change From Baseline in Concurrent Medications | Up to 3 months | Initiation or discontinuation of any medications occurring over the course of the study; monitored by clinician and study personnel. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 25 |
| 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. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Cognitively Relapsing Patients | Stable Multiple Sclerosis Patients | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 25 Participants | 50 Participants |
| Age, Continuous | 42.4 years STANDARD_DEVIATION 10.7 | 43.8 years STANDARD_DEVIATION 10.5 | 43.1 years STANDARD_DEVIATION 10.6 |
| Brief Visuospatial Memory Test Revised (BVMTR) | 23.1 Total Learning Score STANDARD_DEVIATION 7.1 | 23.9 Total Learning Score STANDARD_DEVIATION 7 | 23.5 Total Learning Score STANDARD_DEVIATION 7.1 |
| California Verbal Learning Test, 2nd Edition | 51.4 Total Learning Score STANDARD_DEVIATION 12.6 | 49.1 Total Learning Score STANDARD_DEVIATION 11.1 | 50.3 Total Learning Score STANDARD_DEVIATION 11.9 |
| Expanded Disability Status Scale (EDSS) | 2.5 Total Score | 2.5 Total Score | 2.5 Total Score |
| Fatigue Severity Scale (FSS) | 4.9 Total Score STANDARD_DEVIATION 1.6 | 4.2 Total Score STANDARD_DEVIATION 1.5 | 4.6 Total Score STANDARD_DEVIATION 1.6 |
| Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) | 30.1 Total Score STANDARD_DEVIATION 12.6 | 18.0 Total Score STANDARD_DEVIATION 8.9 | 24.1 Total Score STANDARD_DEVIATION 10.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Female | 20 Participants | 22 Participants | 42 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
| Symbol Digit Modalities Test | 55.2 Total Correct STANDARD_DEVIATION 13.5 | 55.9 Total Correct STANDARD_DEVIATION 12.4 | 55.6 Total Correct STANDARD_DEVIATION 13 |
| Timed 25-foot Walk | 5.4 Seconds STANDARD_DEVIATION 1.9 | 5.0 Seconds STANDARD_DEVIATION 1.2 | 5.2 Seconds STANDARD_DEVIATION 1.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Change From Baseline on the Brief Visuospatial Memory Test-Revised (BVMT-R)
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.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the Brief Visuospatial Memory Test-Revised (BVMT-R) | 22.0 Total Learning Score | Standard Deviation 8.9 |
| Stable Multiple Sclerosis Patients | Change From Baseline on the Brief Visuospatial Memory Test-Revised (BVMT-R) | 22.5 Total Learning Score | Standard Deviation 7.9 |
Primary
Change From Baseline on the California Verbal Learning Test, Second Edition (CVLT-II)
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.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the California Verbal Learning Test, Second Edition (CVLT-II) | 46.6 Total Learning Score | Standard Deviation 14.1 |
| Stable Multiple Sclerosis Patients | Change From Baseline on the California Verbal Learning Test, Second Edition (CVLT-II) | 51.2 Total Learning Score | Standard Deviation 11.8 |
Primary
Change From Baseline on the Paced Auditory Serial Addition Test (PASAT)
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.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the Paced Auditory Serial Addition Test (PASAT) | 40.1 Total Correct | Standard Deviation 12.2 |
| Stable Multiple Sclerosis Patients | Change From Baseline on the Paced Auditory Serial Addition Test (PASAT) | 47.0 Total Correct | Standard Deviation 14.3 |
Primary
Change From Baseline on the Symbol Digit Modalities Test (SDMT)
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.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the Symbol Digit Modalities Test (SDMT) | 44.6 Total Correct | Standard Deviation 13.9 |
| Stable Multiple Sclerosis Patients | Change From Baseline on the Symbol Digit Modalities Test (SDMT) | 58.5 Total Correct | Standard Deviation 13.9 |
Primary
Timed 25-foot Walk
An MS-specific measure of functional status walking speed. How many seconds does it take to walk 25 feet. Ceiling value of 300 seconds.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Timed 25-foot Walk | 6.7 Seconds | Standard Deviation 3.2 |
| Stable Multiple Sclerosis Patients | Timed 25-foot Walk | 5.3 Seconds | Standard Deviation 1.2 |
Secondary
Change From Baseline on the Beck Depression Inventory-Fast Screen (BDI-FS)
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.
Time frame: Day 0 and Day 90
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the Beck Depression Inventory-Fast Screen (BDI-FS) | 5.0 Total Score | Standard Deviation 4 |
| Stable Multiple Sclerosis Patients | Change From Baseline on the Beck Depression Inventory-Fast Screen (BDI-FS) | 1.6 Total Score | Standard Deviation 2.8 |
Secondary
Change From Baseline on the Expanded Disability Status Scale (EDSS).
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.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the Expanded Disability Status Scale (EDSS). | 3.0 Total Score |
| Stable Multiple Sclerosis Patients | Change From Baseline on the Expanded Disability Status Scale (EDSS). | 2.0 Total Score |
Secondary
Change From Baseline on the Fatigue Severity Scale (FSS)
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.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the Fatigue Severity Scale (FSS) | 5.4 Total Score | Standard Deviation 1.4 |
| Stable Multiple Sclerosis Patients | Change From Baseline on the Fatigue Severity Scale (FSS) | 3.8 Total Score | Standard Deviation 1.7 |
Secondary
Change From Baseline on the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ)
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.
Time frame: Day 0 and Day 90
Population: The sample used for final analysis was smaller than the total enrolled (see Participant Flow) because participants were excluded from the final analysis due to (1) withdrawal prior to follow-up, (2) occasional missing data from one or more timepoints, and (3) to optimize matching of the groups based on demographic characteristics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitively Relapsing Patients | Change From Baseline on the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) | 34.5 Total Score | Standard Deviation 9.4 |
| Stable Multiple Sclerosis Patients | Change From Baseline on the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) | 20.0 Total Score | Standard Deviation 12.3 |
Other Pre-specified
Change From Baseline in Concurrent Medications
Initiation or discontinuation of any medications occurring over the course of the study; monitored by clinician and study personnel.
Time frame: Up to 3 months
Other Pre-specified
Incidence of Adverse Events
The number of patients reporting adverse events over the course of the study
Time frame: Up to 3 months