Peripheral Modulation of Muscle Stiffness and Spasticity

• Status: Recruiting
• Trial end date: 2023-11-16
• Target enrollment: 0
• Participant gender: All

Summary

This is a single-center, double-blind, randomized, placebo-controlled, cross-over Phase II trial of human recombinant hyaluronidase injections in individuals with post-stroke upper limb muscle stiffness. The investigators will recruit 50 subjects, 25 males and 25 females, who will be randomized to receive either hyaluronidase plus saline (treatment arm, n=25) or normal saline (control arm, n=25) injections (first injection) in Phase 1 of the study over 5 visits that will test all 3 study aims. Then subjects will cross over to Phase 2 to receive a second injection, where the treatment arm will receive the placebo and the placebo arm will receive the treatment. It is expected that approximately 50 participants will be enrolled to produce 42 evaluable participants. This design will ensure that all subjects receive the drug treatment, which will facilitate recruitment. The injecting physician (PI), the assessors, and the patients will be blind to group assignment. Randomization will be initiated by the IDS pharmacy as per the study statistician. All patients will be assessed at seven visits over 9 weeks of the study: Visit 1 - screening and baseline assessment of aims 1 and 2 (week 1-2); Visit 2 - pre-injection MRI for aim 3 (week 1-2); Visit 3 - first injection (week 2); Visit 4 - post-injection MRI (week 3-5); Visit 5 - post-injection follow up for aims 1 and 2 (week 3-5); CROSSOVER TO OPPOSITE TREATMENT ARM Visit 6 - Second injection (week 6); Visit 7

• post-injection follow-up for aims 1 and 2/ final study visit (week 7-9). There will be no MRI assessment after the second injection as the technique is adequately sensitive to demonstrate changes with a small sample size. The investigators will follow the patients for approximately 9 weeks in this study. After obtaining informed consent, subjects will be screened to ensure that the subjects meet study criteria.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University; New York University School of Medicine
• Collaborator: National Institutes of Health (NIH)

Criteria

Inclusion Criteria:

• Ischemic or hemorrhagic stroke 6-120 months prior

• Moderately-severe muscle stiffness, score of 2-3

• Lack of full passive and active range of motion in at least 2/4 areas (shoulder, elbow, forearm, wrist) in the hemiparetic upper limb;

• Willingness to have MRI, complete all clinical assessments, and comply with study protocols;

• Ability to give informed consent and HIPPA certifications; and

Exclusion Criteria:

• treatment of spasticity with Botulinum toxin or intrathecal baclofen within the past six months;

• other neurologic condition that may affect motor response (e.g., Parkinson's disease, ALS, MS);

• clinically significant cognitive dysfunction with score <24 on Folstein's Mini Mental Status Examination or depression with score >10 on the PHQ-9;

• pregnancy;

• known hypersensitivity to hyaluronidase;

• claustrophobia;

• standard contraindications for MRI

• Any condition that will preclude the patient from completing the protocol as determined by the PI