Peripheral Modulation of Muscle Stiffness and Spasticity

• ClinicalTrials.gov Identifier: NCT03306615
• Recruitment Status: Recruiting
• First Posted: October 11, 2017
• Last Update Posted: October 31, 2022
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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 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 join the 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, 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.

Condition or disease	Intervention/treatment	Phase
Muscle Spasticity	Drug: Hyaluronidase; Drug: Placebo	Phase 2

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 total passive ROM across the affected shoulder, elbow and forearm as measured by motion analysis (primary outcome), isometric muscle strength or force generation capacity using MVC on 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, 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 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Peripheral Modulation of Muscle Stiffness and Spasticity
• Actual Study Start Date: October 11, 2021
• Estimated Primary Completion Date: November 16, 2023
• Estimated Study Completion Date: November 16, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Total upper limb passive range of motion [ Time Frame: 9 weeks ]
   passive range of motion in shoulder, elbow and forearm joints

Secondary Outcome Measures :

1. Total upper limb active range of motion [ Time Frame: 9 weeks ]
   active range of motion in shoulder, elbow and forearm joints
2. Change in upper limb Fugl-Meyer Assessment Score [ Time Frame: 9 weeks ]
   measures motor impairment in the affected upper limb, Score range is 0-66, and a higher score indicates a better outcome
3. Change in Wolf-Motor Function Test (WMFT) Score [ Time Frame: 9 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

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Ischemic or hemorrhagic stroke 6-120 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, 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

Contacts and Locations

Contacts

Contact: Layla Murray, BA; 410-955-1347; lmurra41@jhu.edu

Contact: Matthew Bird, MA; 4109551381; mbird6@jhmi.edu

Locations

United States, Maryland

Paria Arfa Fatollahkhani, MD, M.Sc.; Recruiting

Baltimore, Maryland, United States, 21231

Contact: Paria Arfa Fatollahkhani, MD, MSc parfafa1@jhmi.edu

Contact: Matthew Bird, MA 410-955-1381 mbird6@jhmi.edu

Principal Investigator: Pablo Celnik, MD

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Pablo Celnik, MD; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03306615
• Other Study ID Numbers: IRB00273264
• First Posted: October 11, 2017
• Last Update Posted: October 31, 2022
• Last Verified: October 2022

• 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

Keywords provided by Johns Hopkins University:

Muscle Stiffness; Muscle Spasticity; Stroke; Cerebral Palsy; Hyperreflexia

Additional relevant MeSH terms:

Muscle Spasticity; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases