Clinical trial NCT03306615: Peripheral Modulation of Muscle Stiffness and Spasticity
Official title: Peripheral Modulation of Muscle Stiffness and Spasticity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Muscle Spasticity
Keywords: Muscle Stiffness
Muscle Spasticity
Stroke
Cerebral Palsy
Hyperreflexia
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Sheikh Khalifa Stroke Institute
First posted: 2017-10-11
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Most affected upper limb joint passive range of motion (Cohort 1)
timeFrame: 9 weeks
measure: Most affected upper limb joint passive range of motion (Cohort 2)
timeFrame: 15 weeks
Secondary outcomes:
measure: Total upper limb passive and active range of motion
timeFrame: 15 weeks
measure: Change in upper limb Fugl-Meyer Assessment Score
timeFrame: 15 weeks
measure: Change in Wolf-Motor Function Test (WMFT) Score
timeFrame: 15 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Ning Cao, MD
role: PRINCIPAL_INVESTIGATOR
References: