Peripheral Modulation of Muscle Stiffness and Spasticity

Phase 2

Recruiting

• Conditions: Muscle Spasticity
• Interventions: Drug: Placebo; Drug: Hyaluronidase

• Registration Number: NCT03306615
• Lead Sponsor: Johns Hopkins University

Brief Summary

This is a single-center, double-blind, randomized, placebo-controlled, sequential Phase II trial of human recombinant hyaluronidase injections in individuals with post-stroke upper limb muscle stiffness. The investigators will recruit 56 subjects, who will be randomized to receive either the intervention or normal saline injections (first injection), and then the intervention the participants did not receive first (second injection). All individuals will receive the treatment by the end of the study.

Detailed Description

1. To test the effect of hyaluronidase injections on upper limb outcomes. The investigators will test the hypothesis that compared to placebo, human recombinant hyaluronidase injections will increase passive range of motion (ROM) in the most affected joint of the upper limb (primary outcome), isometric muscle strength or force generation capacity using Maximum Voluntary Contraction (MVC) on electromyography (EMG), reduce upper limb motor impairment as measured by the Fugl-Meyer (FM) scale, and improve function as measured by the Wolf Motor Function Test (WMFT).

2. To evaluate the effect of hyaluronidase on neural and non-neural components of muscle stiffness. The investigators will test the hypothesis that compared to placebo, intramuscular (IM) hyaluronidase will modulate the passive and potentially also the active component of the stretch reflex, reduce stiffness and improve arm motor control.

3. To determine the effect of hyaluronidase on intramuscular glycosaminoglycans (GAG) content. The investigators will test the hypothesis that compared to placebo, IM hyaluronidase will reduce the T1rho relaxation times in the biceps and triceps muscles of the affected arm.

Study Timeline

• Study First Submitted: 2017-10-03
• Study First Submitted QC: 2017-10-09
• Study First Posted: 2017-10-11
• Study Start: 2021-10-11
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-07
• Last Update Posted: 2025-04-09
• Primary Completion: 2025-11-16
• Study Completion: 2025-11-16

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• Ischemic or hemorrhagic stroke 4-180 months prior
• Moderately-severe muscle stiffness
• 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, phenol injections within the past 12 months, or ongoing adjustment of anti-spastic medications;
• other neurologic condition that may affect motor response (e.g., Parkinson's disease, amyotrophic lateral sclerosis (ALS), MS);
• clinically significant cognitive dysfunction with score <19 on Folstein's Mini Mental Status Examination or depression with score >10 on the Patient Health Questionnaire-9 (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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Arm	Placebo	Normal Saline
Treatment Arm	Hyaluronidase	Hyaluronidase plus saline

Primary Outcome Measures

Name	Time	Method
Most affected upper limb joint passive range of motion (Cohort 1)	9 weeks	passive range of motion in most affected joint across the upper limb
Most affected upper limb joint passive range of motion (Cohort 2)	15 weeks	passive range of motion in most affected joint across the upper limb

Secondary Outcome Measures

Name	Time	Method
Total upper limb passive and active range of motion	15 weeks	passive and active range of motion in shoulder, elbow and forearm joints
Change in upper limb Fugl-Meyer Assessment Score	15 weeks	measures motor impairment in the affected upper limb, Score range is 0-66, and a higher score indicates a better outcome
Change in Wolf-Motor Function Test (WMFT) Score	15 weeks	Measures upper extremity function following stroke, Includes 6 items, with a 0-5 score range for each item, and a higher score indicates a better outcome

Trial Locations

Locations (1)

Johns Hopkins School of Medicine; 🇺🇸 Baltimore, Maryland, United States