Safety and Tolerability of ISX (Isoxsuprine HCL) in MS Relapses

NCT03752307 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 18-643
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 12

Secondary Outcomes (1)

• Incidence of Adverse Event Expanded Disability Status Scale (EDSS)

  Baseline to Week 12

Study Arms (2)

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

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

Drug: Placebo; Drug: Corticosteroid

Interventions

Isoxsuprine Hydrochloride DRUG

Compounded Isoxsuprine hydrochloride capsules

Also known as: Duvadilan

Corticosteroid & Isoxsuprine HCL

Placebo DRUG

Identical microcrystalline cellulose placebo manufactured to mimic Isoxsuprine Hydrochloride 10 MG capsules

Corticosteroid & Placebo

Corticosteroid DRUG

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

Also known as: Methylprednisolone, Prednisone

Corticosteroid & Isoxsuprine HCL; Corticosteroid & Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. 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.
• \. 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.
• \. 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.
• \. Subject must be willing to take a high dose steroid (600mg oral prednisone two times a day (bid).
• \. 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.
• \. Subjects must be able to communicate effectively with study personnel. For this reason only English speaking subjects will be eligible for the study.
• \. Subjects must be able and willing to follow all protocol requirements and study restrictions.
• \. Subjects must be able and willing to return for all study visits.

You may not qualify if:

• \. 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.
• \. Subject has only sensory, bowel/bladder, and/or cognitive symptoms of MS associated with the most recent relapse.
• \. 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.
• \. 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.
• 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.
• \. 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

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

University of New Mexico MS Specialty Clinic

Albuquerque, New Mexico, 87106, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Isoxsuprine; Adrenal Cortex Hormones; Methylprednisolone; Prednisone

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Phenethylamines; Ethylamines; Amines; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Results Point of Contact

• Title: Corey Ford, M.D., Ph.D.
• Organization: University of New Mexico

cford@salud.unm.edu

505-925-4124

Study Officials

• Corey C Ford, M.D., Ph.D.

  University of New Mexico

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Subjects will be randomized 1:1 according to a computer-generated allocation scheme to receive either Isoxsuprine HCL 1 capsule 3 times daily for 5 days or matching placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Associate Dean for Research, Office of Research

Model Details: 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

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: November 23, 2018
• Study Start: February 15, 2019
• Primary Completion: July 6, 2023
• Study Completion: July 6, 2023
• Last Updated: February 6, 2024
• Results First Posted: February 6, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)