Peripheral Modulation of Muscle Stiffness and Spasticity

NCT ID: NCT03306615

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-11
• Study Completion Date: 2026-06-30

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.

Conditions

Muscle Spasticity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment Arm

Hyaluronidase plus saline

Group Type: EXPERIMENTAL

Hyaluronidase

Intervention Type: DRUG

HYLENEX recombinant, diluted with 0.9% Sodium Chloride Injection

Control Arm

Normal Saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

0.9% Sodium Chloride Injection

Interventions

Hyaluronidase

HYLENEX recombinant, diluted with 0.9% Sodium Chloride Injection

Intervention Type: DRUG

Placebo

0.9% Sodium Chloride Injection

Intervention Type: DRUG

Other Intervention Names

Hylenex; Normal saline

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheikh Khalifa Stroke Institute

UNKNOWN

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ning Cao, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Azin Etemadimanesh, MD

Role: CONTACT

aetemad2@jhmi.edu

410-955-1347

Robert Nickl, PhD

Role: CONTACT

rnickl1@jhmi.edu

4109551381

Facility Contacts

Azin Etemadimanesh, MD

Role: primary

aetemad2@jhmi.edu

410-955-1347

Other Identifiers

IRB00273264

Identifier Type: -

Identifier Source: org_study_id