Peripheral Modulation of Muscle Stiffness and Spasticity
Primary Purpose
Muscle Spasticity
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hyaluronidase
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Muscle Spasticity focused on measuring Muscle Stiffness, Muscle Spasticity, Stroke, Cerebral Palsy, Hyperreflexia
Eligibility 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
Sites / Locations
- Paria Arfa Fatollahkhani, MD, M.Sc.Recruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment Arm
Control Arm
Arm Description
Hyaluronidase plus saline
Normal Saline
Outcomes
Primary Outcome Measures
Total upper limb passive range of motion
passive range of motion in shoulder, elbow and forearm joints
Secondary Outcome Measures
Total upper limb active range of motion
active range of motion in shoulder, elbow and forearm joints
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
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
Full Information
NCT ID
NCT03306615
First Posted
October 3, 2017
Last Updated
October 13, 2023
Sponsor
Johns Hopkins University
1. Study Identification
Unique Protocol Identification Number
NCT03306615
Brief Title
Peripheral Modulation of Muscle Stiffness and Spasticity
Official Title
Peripheral Modulation of Muscle Stiffness and Spasticity
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2021 (Actual)
Primary Completion Date
November 16, 2023 (Anticipated)
Study Completion Date
November 16, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Spasticity
Keywords
Muscle Stiffness, Muscle Spasticity, Stroke, Cerebral Palsy, Hyperreflexia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
Hyaluronidase plus saline
Arm Title
Control Arm
Arm Type
Placebo Comparator
Arm Description
Normal Saline
Intervention Type
Drug
Intervention Name(s)
Hyaluronidase
Other Intervention Name(s)
Hylenex
Intervention Description
HYLENEX recombinant, diluted with 0.9% Sodium Chloride Injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal saline
Intervention Description
0.9% Sodium Chloride Injection
Primary Outcome Measure Information:
Title
Total upper limb passive range of motion
Description
passive range of motion in shoulder, elbow and forearm joints
Time Frame
9 weeks
Secondary Outcome Measure Information:
Title
Total upper limb active range of motion
Description
active range of motion in shoulder, elbow and forearm joints
Time Frame
9 weeks
Title
Change in upper limb Fugl-Meyer Assessment Score
Description
measures motor impairment in the affected upper limb, Score range is 0-66, and a higher score indicates a better outcome
Time Frame
9 weeks
Title
Change in Wolf-Motor Function Test (WMFT) Score
Description
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
Time Frame
9 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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, ALS, MS);
clinically significant cognitive dysfunction with score <19 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Azin Etemadimanesh, MD
Phone
410-955-1347
Email
aetemad2@jhmi.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Nickl, PhD
Phone
4109551381
Email
rnickl1@jhmi.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ning Cao, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Paria Arfa Fatollahkhani, MD, M.Sc.
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paria Arfa Fatollahkhani, MD, MSc
Email
parfafa1@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Robert Nickl, PhD
Phone
410-955-1381
Email
rnickl1@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Ning Cao, MD
12. IPD Sharing Statement
Learn more about this trial
Peripheral Modulation of Muscle Stiffness and Spasticity
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