Peripheral Modulation of Muscle Stiffness and Spasticity

Sponsor

Johns Hopkins University (Other)

Overall Status

Recruiting

CT.gov ID

NCT03306615

Collaborator

(none)

Enrollment

Location

Arms

25.2

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a single-center, double-blind, randomized, placebo-controlled, cross-over 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 cross over to 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 (PI), 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

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 ROM as measured by motion analysis (primary outcome), isometric muscle strength 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).
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.
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

Anticipated 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 :

Oct 11, 2021

Anticipated Primary Completion Date :

Nov 16, 2023

Anticipated Study Completion Date :

Nov 16, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Hyaluronidase plus saline	Drug: Hyaluronidase 1200 units (8 vials) of HYLENEX recombinant, will be diluted with 8 ml of 0.9% Sodium Chloride Injection, USP - Preservative-Free, Diluent in a 1:1 ratio (total volume = 16 mL) and dispensed in two 10 ml syringes (8ml in each syringe) for intramuscular injection. Other Names: Hylenex
Placebo Comparator: Control Arm Normal Saline	Drug: Placebo The placebo will consist of 16 ml of 0.9% Sodium Chloride Injection, USP - Preservative-Free, also dispensed in two 10 ml syringes for intramuscular injection. The label will include a statement that the product is limited to investigational use, and the original drug containers will be retained.

Arm

Intervention/Treatment

Experimental: Treatment Arm

Hyaluronidase plus saline

Drug: Hyaluronidase

1200 units (8 vials) of HYLENEX recombinant, will be diluted with 8 ml of 0.9% Sodium Chloride Injection, USP - Preservative-Free, Diluent in a 1:1 ratio (total volume = 16 mL) and dispensed in two 10 ml syringes (8ml in each syringe) for intramuscular injection.

Other Names:

Hylenex

Placebo Comparator: Control Arm

Normal Saline

Drug: Placebo

The placebo will consist of 16 ml of 0.9% Sodium Chloride Injection, USP - Preservative-Free, also dispensed in two 10 ml syringes for intramuscular injection. The label will include a statement that the product is limited to investigational use, and the original drug containers will be retained.

Outcome Measures

Primary Outcome Measures

limb passive range of motion using Edinburgh Handedness Inventory [9 weeks]
measurement scale used to assess the dominance of a person's right or left hand in everyday activities, sometime referred to as laterality.
limb active range of motion using Edinburgh Handedness Inventory [9 weeks]
measurement scale used to assess the dominance of a person's right or left hand in everyday activities, sometime referred to as laterality.
Change in Modified Ashworth Scale Score [9 weeks]
measures resistance during passive soft- tissue stretching

Secondary Outcome Measures

Quality of Life Measured by Patient Health Questionnaire-9 (PHQ-9) assessment scale [9 weeks]
multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression.
Change in Folstein's Mini Mental Status [9 weeks]
tool that can be used to systematically and thoroughly assess mental status. It is an 11-question measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall, and language. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The MMSE takes only 5-10 minutes to administer and is therefore practical to use repeatedly and routinely.
Fugl-Meyer Motor assessment score [9 weeks]
stroke-specific, performance-based impairment index.
Change in Wolf-Motor Function Test (WMFT) Score [9 weeks]
Measures upper extremity motion following stroke

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ischemic or hemorrhagic stroke 6-120 months prior
Moderately-severe muscle stiffness, score of 2-3
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;
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