Peripheral Modulation of Muscle Stiffness and Spasticity

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Muscle Spasticity
• Intervention / Treatment: Drug: Hyaluronidase; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Hyaluronidase plus saline	Drug: Hyaluronidase; HYLENEX recombinant, diluted with 0.9% Sodium Chloride Injection; Other Names: Hylenex
Placebo Comparator: Control Arm; Normal Saline	Drug: Placebo; 0.9% Sodium Chloride Injection; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Most affected upper limb joint passive range of motion (Cohort 1)	passive range of motion in most affected joint across the upper limb	9 weeks
Most affected upper limb joint passive range of motion (Cohort 2)	passive range of motion in most affected joint across the upper limb	15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total upper limb passive and active range of motion	passive and active range of motion in shoulder, elbow and forearm joints	15 weeks
Change in upper limb Fugl-Meyer Assessment Score	measures motor impairment in the affected upper limb, Score range is 0-66, and a higher score indicates a better outcome	15 weeks
Change in Wolf-Motor Function Test (WMFT) Score	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	15 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Sheikh Khalifa Stroke Institute
• Investigators: Principal Investigator: Ning Cao, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 3, 2017
• First Submitted That Met QC Criteria: October 9, 2017
• First Posted (Actual): October 11, 2017

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cerebral Palsy; Stroke; Muscle Spasticity; Muscle Stiffness; Hyperreflexia
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Brain Damage, Chronic; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Muscle Spasticity; Stroke; Cerebral Palsy; Reflex, Abnormal; Pharmaceutical Preparations; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Crystalloid Solutions; Isotonic Solutions; Solutions; Hyaluronoglucosaminidase; Saline Solution
• Other Study ID Numbers: IRB00273264

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No