Relapsing Remitting Multiple Sclerosis
Conditions
Brief summary
Tolerability of Acthar for the Treatment of Multiple Sclerosis Relapses (TAMS)
Detailed description
We propose to conduct a prospective, single-center, open-label, single-arm study comparing tolerability of Acthar versus oral prednisone in the treatment of MS relapses. Potential subjects will be identified during routine clinical evaluations. If patient is determined to be having a study-defined MS relapse, they will be invited to participate in this study. After consent is obtained, the patient will complete the first page of the ARMS survey. If prior steroid use was deemed tolerable then only the first page of the ARMS will be collected and analyzed and these patients will complete their participation in the trial. Their data from the ARMS will provide an estimate as to the number of patients who self-report tolerability and efficacy issues with steroids. However, if patients self-report prior steroid intolerability, then they will advance into the Acthar treatment arm of the trial.
Interventions
DRUGActhar
Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults.
Sponsors
OhioHealth
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Subjects who have volunteered and consented to participate in the study. 2. Subjects who have no contraindication to taking high dose, oral prednisone or Acthar. 3. Male or Female subjects age 18 or greater years of age. 4. Subjects with Relapsing Remitting Multiple Sclerosis (RRMS) based on 2010 McDonald Criteria. 5. Subjects without an active infection (Note: If a patient is found to have an uncomplicated UTI and agrees to start on appropriate antibiotic treatment, they can continue in the study). 6. Subjects who are experiencing a protocol defined MS relapse within two weeks of relapse onset. 7. Subjects who are able and willing to sign a consent form.
Exclusion criteria
1. Subjects who are less than 18 years of age. 2. Subjects with any contraindication to taking Acthar. 3. Subjects with an active infection other than an uncomplicated urinary tract infection (UTI) (subjects determined to have a UTI who agree to be treated with appropriate antibiotics will not be excluded). 4. Subjects with an immune deficiency. 5. Subjects with a history of any of the following conditions: gastrointestinal ulcers, diabetes mellitus, gestational diabetes, malignant hypertension or steroid induced psychosis. 6. Subjects who are pregnant or breastfeeding. 7. Subjects who are unable or unwilling to sign consent form. 8. Patient is unable or unwilling to participate in phone and clinic follow up. 9. Other factors that in the opinion of the Principal Investigator would exclude the subject from participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SAGE (Self-administered Gerocognitive Exam) Scores | baseline and follow-up | The Self-Administered Gerocognitive Exam (SAGE) is designed to detect early signs of cognitive, memory or thinking impairments. It evaluates your thinking abilities and helps physicians to know how well your brain is working. It consists of 12 questions which are scored at different scales. The final SAGE score is calculated as a sum of these 12 questions and it ranges from 0 to 22. Higher score indicates better outcome. |
| ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living) | baseline visit & follow-up after treatment | Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, history of patients from the survey after treatment for the new relapse will be collected. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. ADL scores were calculated from Part 1 (new relapse), question 3 and Part 2 (after treatment of relapse), question 5 both specifically refer to ADL; Scale: ADL (Activities of Daily Living) Minimum value: 0 Maximum value: 9 Higher scores indicated better functioning/ improvement. |
| ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health) | baseline visit & follow-up after treatment | Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. Part 1 (new relapse) & Part 2 (after treatment of new relapse), question 6 were used to calculate RSH; Scale: RSH (Return to previous health) Minimum value: -1 Maximum value: 10 Higher scores indicating a more complete return to previous state of health. |
| ARMS (Assessing Relapses in Multiple Sclerosis) TCS Scores (Total Composite Scores) | Follow-up visit | Patients completed the ARMS survey after treatment for the new relapse.The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. The TCS score was calculated only for the time point after treatment of relapse. It was a sum of questions 4 (symptom improvement), 5 (ADL), and 6 (return to previous state of health (RSH)) were evaluated. Scores range from 0 to 30 units, with higher scores representing greater improvement/better functioning. |
| ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores) | baseline visit & follow-up after treatment | Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. PCS was computed based on the sum of the ADL and RSH questions. The PCS was computed separately for Part 1 (new relapse) and Part 2 (after relapse treatment) and summarized descriptively; Higher scores indicating better functioning/greater improvement. The PCS scores were on a scale of 0 to 20 units. |
| MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score | baseline visit & follow-up after treatment | The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS. The physical impact of MS was compared between pre and post phase using paired t-tests. Each question is answered with points ranging from 1 to 5. Higher score indicates worse outcome. The total MSIS physical score ranges from 20 to 100 points with lower points indicating better impact. |
| MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score. | baseline visit & follow-up after treatment | The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS and 9 questions assess the psychological impact of MS. The psychological impact of MS was compared between pre and post phase using paired t-tests. The psychological impact of MS was compared between pre and post phase using paired t-tests. The score was on a scale of 9 to 45 points for MSIS psychological score. Higher score indicate worse outcome. |
| EDSS (Expanded Disability Status Scale) Scores. | baseline and at follow-up | This scaling score is obtained by performing a neurologic exam with specific attention to eight different neurologic functional systems: visual, pyramidal, cerebellar, bowel and bladder, cerebral, brainstem, sensory and other (10). The score is rated from zero (normal neurologic examination) to ten (death due to MS). This is the standard neurologic disability scale used in clinical trials for the evaluation of disability in patients with MS. These scores were compared between pre and post phase using paired t-tests. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GASE Scale Questionnaire (Generic Assessment of Side Effects) | 1 week | Patients who reported a history of poor corticosteroid tolerability will be placed on Acthar and GASE scale will be given to assess tolerability to Acthar. We listed the number of times a symptom was reported and was attributable to the ACTHAR treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Acthar 80 units subcutaneously for five consecutive days.
Acthar: Is indicated for the treatment of acute exacerbations of multiple sclerosis in adults. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Single Arm |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 38.4 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living)
Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, history of patients from the survey after treatment for the new relapse will be collected. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. ADL scores were calculated from Part 1 (new relapse), question 3 and Part 2 (after treatment of relapse), question 5 both specifically refer to ADL; Scale: ADL (Activities of Daily Living) Minimum value: 0 Maximum value: 9 Higher scores indicated better functioning/ improvement.
Time frame: baseline visit & follow-up after treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Arm | ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living) | ADL (new relapse) | 3.1 score on a scale | Standard Deviation 2.2 |
| Single Arm | ARMS (Assessing Relapses in Multiple Sclerosis) ADL Scores (Activities of Daily Living) | ADL (after treatment of relapse) | 4.9 score on a scale | Standard Deviation 2.8 |
Comparison: We compared the two ADL scores measured in the same arm at different timepoints (new \& after treatment).~Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0~We used the Paired t-test to compare the pre - post ADL scores.p-value: 0.00395% CI: [-2.9, -0.66]Paired t-test, 2 sided
Primary
ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores)
Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. PCS was computed based on the sum of the ADL and RSH questions. The PCS was computed separately for Part 1 (new relapse) and Part 2 (after relapse treatment) and summarized descriptively; Higher scores indicating better functioning/greater improvement. The PCS scores were on a scale of 0 to 20 units.
Time frame: baseline visit & follow-up after treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Arm | ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores) | PCS (New relapse) | 7.7 score on a scale | Standard Deviation 3.3 |
| Single Arm | ARMS (Assessing Relapses in Multiple Sclerosis) PCS Scores (Partial Composite Scores) | PCS (after treatment of relapse) | 9.2 score on a scale | Standard Deviation 5.6 |
Comparison: We compared the two PCS scores measured in the same arm at different timepoints (new \& after treatment).~Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0 We used the Paired t-test to compare the pre - post PCS scores.p-value: 0.0395% CI: [-3.67, -0.18]Paired t-test, two sided
Primary
ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health)
Patient history of prior corticosteroid tolerability for the treatment of MS relapses. This will be determined based on patient completion of the ARMS survey at the baseline visit. Also, patients completed the survey after treatment for the new relapse. The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. Part 1 (new relapse) & Part 2 (after treatment of new relapse), question 6 were used to calculate RSH; Scale: RSH (Return to previous health) Minimum value: -1 Maximum value: 10 Higher scores indicating a more complete return to previous state of health.
Time frame: baseline visit & follow-up after treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Single Arm | ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health) | RSH (new relapse) | 4.6 score on a scale | Standard Deviation 2.9 |
| Single Arm | ARMS (Assessing Relapses in Multiple Sclerosis) RSH Scores (Return to Previous Health) | RSH (after treatment of new relapse) | 4.4 score on a scale | Standard Deviation 3.2 |
Comparison: We compared the two RSH scores measured in the same arm at different time points (new \& after treatment).~Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0 We used the Paired t-test to compare the pre - post RSH scores.p-value: 0.9995% CI: [-1.22, 1.22]Paired t-test, 2 sided
Primary
ARMS (Assessing Relapses in Multiple Sclerosis) TCS Scores (Total Composite Scores)
Patients completed the ARMS survey after treatment for the new relapse.The ARMS questionnaire (assessing relapses in multiple sclerosis) was developed by a panel of expert MS nurses. Part one consists of 7 questions designed to assess relapse symptoms, impact on activities of daily living, and response to past treatment for MS relapses. Part two consists of 7 questions to evaluate treatment response in terms of relief from symptoms, functioning and tolerability. The TCS score was calculated only for the time point after treatment of relapse. It was a sum of questions 4 (symptom improvement), 5 (ADL), and 6 (return to previous state of health (RSH)) were evaluated. Scores range from 0 to 30 units, with higher scores representing greater improvement/better functioning.
Time frame: Follow-up visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Single Arm | ARMS (Assessing Relapses in Multiple Sclerosis) TCS Scores (Total Composite Scores) | 14.3 score on a scale | Standard Deviation 8.5 |
Primary
EDSS (Expanded Disability Status Scale) Scores.
This scaling score is obtained by performing a neurologic exam with specific attention to eight different neurologic functional systems: visual, pyramidal, cerebellar, bowel and bladder, cerebral, brainstem, sensory and other (10). The score is rated from zero (normal neurologic examination) to ten (death due to MS). This is the standard neurologic disability scale used in clinical trials for the evaluation of disability in patients with MS. These scores were compared between pre and post phase using paired t-tests.
Time frame: baseline and at follow-up
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Arm | EDSS (Expanded Disability Status Scale) Scores. | EDSS score (new relapse) | 3.5 score on a scale |
| Single Arm | EDSS (Expanded Disability Status Scale) Scores. | EDSS score (after treatment of new relapse) | 3.0 score on a scale |
Comparison: We compared the two EDSS scores measured in the same arm at different timepoints (new relapse \& after treatment of relapse).~Null Hypothesis = Difference in medians is = 0 Alternate Hypothesis = Difference in medians is not = 0~We used the Wilcoxon Signed rank test to compare the pre - post EDSS scores.p-value: 0.23Wilcoxon Signed Rank test
Primary
MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score
The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS. The physical impact of MS was compared between pre and post phase using paired t-tests. Each question is answered with points ranging from 1 to 5. Higher score indicates worse outcome. The total MSIS physical score ranges from 20 to 100 points with lower points indicating better impact.
Time frame: baseline visit & follow-up after treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Arm | MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score | MSIS physical (new relapse) | 58.5 score on a scale |
| Single Arm | MSIS (Multiple Sclerosis Impact Scale) -29 Physical Score | MSIS physical (after treatment of new relapse) | 56 score on a scale |
Comparison: We compared the two MSIS physical scores measured in the same arm at different timepoints (new relapse \& after treatment of relapse).~Null Hypothesis = Difference in medians is = 0 Alternate Hypothesis = Difference in medians is not = 0~We used the Wilcoxon Signed rank test to compare the pre - post MSIS physical scores.p-value: 0.19Wilcoxon Signed Rank test
Primary
MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score.
The MSIS-29 is a self-reported questionnaire in which MS patients answer a series of 29 questions designed to capture the impact of multiple sclerosis on their life over the past 2 weeks (11). Twenty of the 29 questions assess the physical impact of MS and 9 questions assess the psychological impact of MS. The psychological impact of MS was compared between pre and post phase using paired t-tests. The psychological impact of MS was compared between pre and post phase using paired t-tests. The score was on a scale of 9 to 45 points for MSIS psychological score. Higher score indicate worse outcome.
Time frame: baseline visit & follow-up after treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Single Arm | MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score. | MSIS psychological(new relapse) | 29.4 score on a scale |
| Single Arm | MSIS (Multiple Sclerosis Impact Scale) - 29 Psychological Score. | MSIS psychological(after treatment of new relapse) | 26.3 score on a scale |
Comparison: We compared the two MSIS psychological scores measured in the same arm at different timepoints (new relapse \& after treatment of relapse).~Null Hypothesis = Difference in means is = 0 Alternate Hypothesis = Difference in means is not = 0~We used the Paired t-test to compare the pre - post MSIS psychological scores.p-value: 0.0195% CI: [0.74, 5.45]Paired t-test, 2 sided
Primary
SAGE (Self-administered Gerocognitive Exam) Scores
The Self-Administered Gerocognitive Exam (SAGE) is designed to detect early signs of cognitive, memory or thinking impairments. It evaluates your thinking abilities and helps physicians to know how well your brain is working. It consists of 12 questions which are scored at different scales. The final SAGE score is calculated as a sum of these 12 questions and it ranges from 0 to 22. Higher score indicates better outcome.
Time frame: baseline and follow-up
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single Arm | SAGE (Self-administered Gerocognitive Exam) Scores | SAGE (new relapse) | 21 score on a scale |
| Single Arm | SAGE (Self-administered Gerocognitive Exam) Scores | SAGE (after treatment of new relapse) | 21 score on a scale |
Comparison: We compared the two SAGE scores measured in the same arm at different time points (new relapse \& after treatment of relapse).~Null Hypothesis = Difference in medians is = 0 Alternate Hypothesis = Difference in medians is not = 0~We used the Wilcoxon Signed rank test to compare the pre - post SAGE scores.p-value: 0.44Wilcoxon Signed Rank test
Secondary
GASE Scale Questionnaire (Generic Assessment of Side Effects)
Patients who reported a history of poor corticosteroid tolerability will be placed on Acthar and GASE scale will be given to assess tolerability to Acthar. We listed the number of times a symptom was reported and was attributable to the ACTHAR treatment
Time frame: 1 week
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Sweating | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Headache | 3 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Dry Mouth | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Dizziness | 2 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Tachycardia, palpitation or arrhythmia | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Breathing problems | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Abdominal pain | 4 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Nausea | 4 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Diarrhea | 4 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Reduced Appetite | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Increased appetite | 4 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Difficulties with urination | 2 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Skin rash or itching | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Tendency to develop bruises | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Hot flashes | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Fatigue, loss of energy | 2 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Insomnia, sleeping problems | 8 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Nightmares or abnormal dreams | 2 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Back pain | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Agitation | 6 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Irritability | 6 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Depressed Mood | 3 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Anxiety, fearfulness | 1 Participants |
| Single Arm | GASE Scale Questionnaire (Generic Assessment of Side Effects) | Further symptoms | 8 Participants |