Multiple SclerosisPhase 1/2NCT03752307
Safety and Tolerability of ISX (Isoxsuprine HCL) in MS Relapses
A Phase 1/2 study testing Isoxsuprine Hydrochloride and Corticosteroid in people with Multiple Sclerosis, run by University of New Mexico at 1 site in United States.
Trial summary
This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse. Evidence from preclinical stroke models and experimental allergic encephalomyelitis suggest that isoxsuprine hydrochloride may have neuroprotective… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Isoxsuprine Hydrochloride and Corticosteroid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2019to 6 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 1. Subjects must be adequately informed and understand the nature and risks of the study and must be able to provide a signature and date on the ICF; 2. Male or female subjects between 18 and 50 years of age, inclusive; 3. Confirmed diagnosis of Multiple Sclerosis or Clinically Isolated Syndrome (CIS) suggestive of MS, according to the 2010 Revised McDonald criteria.
- 4. On a stable regimen of medications taken specifically to treat MS for at least 30 days prior to screening, and willing to continue the same doses and regimens for the duration of study participation; 5. New neurological disability consistent with MS relapse no longer than 7 days prior to screening; 6. Screen visit and randomization must occur within 48 hours of subject initiating steroid treatment.
- 7. Maximum EDSS score during screening of 6.5; 8. Sufficient ambulatory ability (ambulatory aids acceptable if used consistently) to complete two trials of the Timed 25 Foot Walk (T25FW) at the screening visit with the two trials completed within 5 minutes of each other in accordance with the specific instructions provided by the National MS Society Functional Composite Manual.
- 9. Subject must be willing to take a high dose steroid (600mg oral prednisone two times a day (bid).
- 10. Subjects must have a mean systolic blood pressure ≤ 160 and greater than 100 mm Hg and a mean diastolic blood pressure of ≤ 100 and greater than 50 mm Hg determined by the average of 3 seated readings taken at least 5 minutes apart at the Screening Visit.
- 11. Subjects must be able to communicate effectively with study personnel. For this reason only English speaking subjects will be eligible for the study.
- 12. Subjects must be able and willing to follow all protocol requirements and study restrictions.
- 13. Subjects must be able and willing to return for all study visits.
Who cannot join
- 1. Subject is from a vulnerable population, as defined by the US CFR Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the IRB.
- 2. Subject has only sensory, bowel/bladder, and/or cognitive symptoms of MS associated with the most recent relapse.
- 3. Subject has cognitive or behavioral impairment that in the opinion of the investigator would impair the ability of the subject to comply with study procedures.
- 4. Subject has any known contraindication(s) to the use of corticosteroids or isoxsuprine hydrochloride (ISX), including, but not limited to:
- any current uncontrolled hypertension, primary adrenocortical insufficiency
- Any current psychoses, infectious disease, or Cushing's syndrome.
Show all 12Show fewer
- Any current congestive heart failure (defined as New York Heart Association (Functional Class III to IV).
- Peptic ulcer (within 24 weeks prior to the Screening Visit).
- Recent major surgery (within 24 weeks prior to the Screening Visit).
- Use of tizanidine any time in the past 30 days. 5. Subject has a clinically significant infection requiring intravenous administration of antibiotics and hospitalization prior to the Screening Visit.
- 6. Subject has poorly controlled type 1 or type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not exclusionary 7. Received systemic steroids for a problem unrelated to the MS relapse within 30 days prior to screening.
- 8. History of other neurological disease that, 'in the opinion of the Investigator, would affect motor function or cognition; 9. For patients with a history of Major Depressive Disorder, at risk for worsening depression due to steroids or the presence of active depressive symptoms sufficient, in the opinion of the investigator, to affect the subject's ability to complete study assessments, or which would not be in the subject's best Interest to participate in the study; 10. Presence of cognitive impairment sufficient, in the opinion of the investigator, to affect the subject's ability to complete study assessments, or which would not be In the subject's best interest to participate in the study 11. History of sensory impairments (e.g., hearing, vision) that, In the opinion of the investigator, would impair the subject's ability to complete study assessments; 12. History of current alcohol or substance abuse or dependence; 13. History of myocardial infarction, or NYHA Functional Classification of Heart Failure Class 3 or 4 within 2 years prior to screening, or history of coronary artery disease and/or active angina pectoris; 14. Any clinically significant ECG abnormalities;; 15. Inability to swallow oral capsules, or a history of gastrointestinal malabsorption that would preclude the use of oral medication; 16. If female, is pregnant or lactating; 17. History of hypersensitivity or allergic reaction to any of the study drugs. 18. History of heavy use of tobacco/smoking
Trial locations and contacts
1 site in 1 country.
United States1 site
University of New Mexico MS Specialty Clinic
Albuquerque, New Mexico, 87106
About this study
Official title: Double-blind, Placebo-controlled, Randomized Study of the Safety and Tolerability of Isoxsuprine HCL Combined With High Dose Steroid Treatment of Multiple Sclerosis (MS) Relapse
This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse.
Evidence from preclinical stroke models and experimental allergic encephalomyelitis suggest that isoxsuprine hydrochloride may have neuroprotective activity and reduce disability in animal models. Given its potential neuroprotective effects in CNS injury models, the investigators propose to test it as a safe, tolerable add on treatment for acute relapses in patients with relapsing forms of MS.
Read the detailed description
This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse.
All subjects will have a documented diagnosis of relapsing MS or a clinically isolated syndrome by international criteria. The relapse will be of sufficient severity that their physician recommends treatment with a high dose corticosteroid pulse. All subjects will have a physical examination and history with questions on drug sensitivities. Subjects experiencing the onset of objective neurological deficits consistent with relapse within 7 days of randomization are eligible for screening for this study. Those currently on MS disease modifying therapy will have received a stable regimen of the medications for at least 30 days prior to screening and will continue the same doses and regimens for the duration of their study participation.
Consented subjects will be assessed for relapse criteria and those who meet study eligibility criteria and agree to be treated with a standard 3 to 5 day pulse of high dose corticosteroids, will be randomized with equal probability to 1 of 2 treatment groups: placebo capsule or active Isoxsuprine (ISX).
The Screening Visit will take place within 7 days of relapse onset and within 48 hours of initiating high dose steroids. Subjects may start corticosteroids anytime during this 7 day window. During the screening period, subjects will be assessed with the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and cognitive testing prior to treatment with ISX or placebo (1:1 ratio). Safety Assessments during screening will include a physical exam, electrocardiogram, vital signs, weight and a urine pregnancy test for females of child bearing potential. At 7 (± 1) days following the completion of the 5-day ISX dosing, subjects will be re-assessed with the EDSS.
Subjects will be evaluated for treatment response using the EDSS and other standard measures.
Study drug will be administered as one (1) 10 mg capsule, 3 times daily for 5 days in conjunction with concomitant dosing with high dose corticosteroids. This can be any accepted regimen, including daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon, with food, as typically provided by UNM MS Specialty Clinic.
- Conditions
- Multiple Sclerosis
- Being tested
- Isoxsuprine Hydrochloride, Placebo, Corticosteroid
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isoxsuprine HydrochlorideDrug
Also called Duvadilan
Compounded Isoxsuprine hydrochloride capsules
PlaceboDrug
Identical microcrystalline cellulose placebo manufactured to mimic Isoxsuprine Hydrochloride 10 MG capsules
CorticosteroidDrug
Also called Methylprednisolone, Prednisone
This can be any accepted regimen, including daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon
| Study group | Role | What they receive |
|---|---|---|
| Corticosteroid & Isoxsuprine HCL | Experimental | Corticosteroid pulse of either daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon for 3 to 5 consecutive days and Isoxsuprine Hydrochloride one 10 mg Capsule 3 times daily for 5 consecutive days Receives: Drug: Isoxsuprine Hydrochloride; Drug: Corticosteroid |
| Corticosteroid & Placebo | Placebo comparator | Corticosteroid pulse of either daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon for 3 to 5 consecutive day and placebo one Capsule 3 times daily for 5 consecutive days Receives: Drug: Placebo; Drug: Corticosteroid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events in Subjects by Measuring Measuring Changes in Vital Signs
Vital Signs: Blood pressure greater than 140/90, pulse greater than 110 and temperature greater than 37.8 Celsius.
Measured: Baseline to Week 12
Secondary outcomes (1)
Incidence of Adverse Event Expanded Disability Status Scale (EDSS)
The unit of measure is 0 (no disability) to 10 (death). An increase in EDSS score from baseline measure during with steroid/study treatment during the study would be considered an adverse event.
Measured: Baseline to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2018
- Study start15 Feb 2019
- Primary completion6 Jul 2023
- Study completion6 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of New Mexico
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Corey C Ford, MD, PhD, University of New Mexico
- Investigators
- Corey C Ford, M.D., Ph.D., Principal investigator, University of New Mexico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03752307
- Sponsor's protocol ID
- 18-643
- Status last verified
- Jan 2024
- First submitted
- 15 Nov 2018
- Last updated
- 6 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared.
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-blind, Placebo-controlled, Randomized Study of the Safety and Tolerability of Isoxsuprine HCL Combined With High Dose Steroid Treatment of Multiple Sclerosis (MS) Relapse
- ClinicalTrials.gov ID
- NCT03752307
- Acronym / sponsor ID
- 18-643
- Conditions
- Multiple Sclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of New MexicoUniversity, hospital or other
- Study start
- 15 Feb 2019 (actual)
- Primary completion
- 6 Jul 2023 (actual)
- Study completion
- 6 Jul 2023 (actual)
- First posted
- 23 Nov 2018 (actual)
- Results
- Posted 6 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse.
Evidence from preclinical stroke models and experimental allergic encephalomyelitis suggest that isoxsuprine hydrochloride may have neuroprotective activity and reduce disability in animal models. Given its potential neuroprotective effects in CNS injury models, the investigators propose to test it as a safe, tolerable add on treatment for acute relapses in patients with relapsing forms of MS.
Detailed description
This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse.
All subjects will have a documented diagnosis of relapsing MS or a clinically isolated syndrome by international criteria. The relapse will be of sufficient severity that their physician recommends treatment with a high dose corticosteroid pulse. All subjects will have a physical examination and history with questions on drug sensitivities. Subjects experiencing the onset of objective neurological deficits consistent with relapse within 7 days of randomization are eligible for screening for this study. Those currently on MS disease modifying therapy will have received a stable regimen of the medications for at least 30 days prior to screening and will continue the same doses and regimens for the duration of their study participation.
Consented subjects will be assessed for relapse criteria and those who meet study eligibility criteria and agree to be treated with a standard 3 to 5 day pulse of high dose corticosteroids, will be randomized with equal probability to 1 of 2 treatment groups: placebo capsule or active Isoxsuprine (ISX).
The Screening Visit will take place within 7 days of relapse onset and within 48 hours of initiating high dose steroids. Subjects may start corticosteroids anytime during this 7 day window. During the screening period, subjects will be assessed with the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and cognitive testing prior to treatment with ISX or placebo (1:1 ratio). Safety Assessments during screening will include a physical exam, electrocardiogram, vital signs, weight and a urine pregnancy test for females of child bearing potential. At 7 (± 1) days following the completion of the 5-day ISX dosing, subjects will be re-assessed with the EDSS.
Subjects will be evaluated for treatment response using the EDSS and other standard measures.
Study drug will be administered as one (1) 10 mg capsule, 3 times daily for 5 days in conjunction with concomitant dosing with high dose corticosteroids. This can be any accepted regimen, including daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon, with food, as typically provided by UNM MS Specialty Clinic.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This is a proof of concept, randomized, double-blind, placebo-controlled, 2-arm, parallel group study of Isoxsuprine in MS subjects experiencing a typical relapse
| Arm | Type | Receives |
|---|---|---|
| Corticosteroid & Isoxsuprine HCL | Experimental | Drug: Isoxsuprine Hydrochloride, Drug: CorticosteroidCorticosteroid pulse of either daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon for 3 to 5 consecutive days and Isoxsuprine Hydrochloride one 10 mg Capsule 3 times daily for 5 consecutive days |
| Corticosteroid & Placebo | Placebo comparator | Drug: Placebo, Drug: CorticosteroidCorticosteroid pulse of either daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon for 3 to 5 consecutive day and placebo one Capsule 3 times daily for 5 consecutive days |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 1. Subjects must be adequately informed and understand the nature and risks of the study and must be able to provide a signature and date on the ICF; 2. Male or female subjects between 18 and 50 years of age, inclusive; 3. Confirmed diagnosis of Multiple Sclerosis or Clinically Isolated Syndrome (CIS) suggestive of MS, according to the 2010 Revised McDonald criteria.
- 4. On a stable regimen of medications taken specifically to treat MS for at least 30 days prior to screening, and willing to continue the same doses and regimens for the duration of study participation; 5. New neurological disability consistent with MS relapse no longer than 7 days prior to screening; 6. Screen visit and randomization must occur within 48 hours of subject initiating steroid treatment.
- 7. Maximum EDSS score during screening of 6.5; 8. Sufficient ambulatory ability (ambulatory aids acceptable if used consistently) to complete two trials of the Timed 25 Foot Walk (T25FW) at the screening visit with the two trials completed within 5 minutes of each other in accordance with the specific instructions provided by the National MS Society Functional Composite Manual.
- 9. Subject must be willing to take a high dose steroid (600mg oral prednisone two times a day (bid).
- 10. Subjects must have a mean systolic blood pressure ≤ 160 and greater than 100 mm Hg and a mean diastolic blood pressure of ≤ 100 and greater than 50 mm Hg determined by the average of 3 seated readings taken at least 5 minutes apart at the Screening Visit.
Key exclusion criteria (12 listed)
- 1. Subject is from a vulnerable population, as defined by the US CFR Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full time, etc) or a family member of the research staff conducting the study, or of the sponsor, or of the IRB.
- 2. Subject has only sensory, bowel/bladder, and/or cognitive symptoms of MS associated with the most recent relapse.
- 3. Subject has cognitive or behavioral impairment that in the opinion of the investigator would impair the ability of the subject to comply with study procedures.
- 4. Subject has any known contraindication(s) to the use of corticosteroids or isoxsuprine hydrochloride (ISX), including, but not limited to:
- 6. Subject has poorly controlled type 1 or type 2 diabetes mellitus (prior diagnosis of gestational diabetes mellitus is not exclusionary 7. Received systemic steroids for a problem unrelated to the MS relapse within 30 days prior to screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isoxsuprine HydrochlorideAlso: DuvadilanCompounded Isoxsuprine hydrochloride capsules | Drug | Corticosteroid & Isoxsuprine HCL |
| PlaceboIdentical microcrystalline cellulose placebo manufactured to mimic Isoxsuprine Hydrochloride 10 MG capsules | Drug | Corticosteroid & Placebo |
| CorticosteroidAlso: Methylprednisolone, PrednisoneThis can be any accepted regimen, including daily iv methylprednisolone 1000 mg/day or 600mg oral prednisone two times a day at approximately 8AM and noon | Drug | Corticosteroid & Isoxsuprine HCL, Corticosteroid & Placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events in Subjects by Measuring Measuring Changes in Vital Signs
Time frame: Baseline to Week 12
Vital Signs: Blood pressure greater than 140/90, pulse greater than 110 and temperature greater than 37.8 Celsius.
1 secondary outcome
Incidence of Adverse Event Expanded Disability Status Scale (EDSS)
Time frame: Baseline to Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Individual participant data will not be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Corey C Ford, M.D., Ph.D. principal investigator
University of New Mexico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Isoxsuprine Hydrochloride and Corticosteroid in people with Multiple Sclerosis, run by University of New Mexico at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events in Subjects by Measuring Measuring Changes in Vital Signs (time frame: Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2024.