Myofascial Dysfunction in Post Stroke Shoulder Pain

NCT06718413 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB003548724R33AT012279-02
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Shoulder pain is extremely common after stroke and occurs in 30-70% of patients. The pain may begin as early as one week after stroke, although peak onset and severity occurs around four months, and persists into the chronic stage. Chronic post stroke shoulder pain (PSSP) interferes with motor recovery, decreases quality of life, and contributes to depression. PSSP is thought to be caused mainly by damage to the myofascial tissues around the shoulder joint. Interestingly, an MRI study in patients with PSSP showed that the degree of structural damage to the muscles did not correlate with the degree of pain. Thus, the pathophysiology of myofascial dysfunction and pain in PSSP has not been elucidated leading to missed opportunities for early diagnosis and variable success with pain management. The accumulation of hyaluronic acid (HA) in muscle and its fascia can cause myofascial dysfunction. HA is a glycosaminoglycan (GAG) consisting of long-chain polymers of disaccharide units of glucuronic acid and N-acetylglucosamine and is a chief constituent of the extracellular matrix of muscle. In physiologic quantities, HA functions as a lubricant and a viscoelastic shock absorber, enabling force transmission during contraction and stretch. Reduced joint mobility and spasticity result in focal accumulation and alteration of HA in muscle. This can lead to the development of stiff areas and taut bands, dysfunctional gliding of deep fascia and muscle layers, reduced range of motion (ROM), and pain. However, the association of muscle HA accumulation with PSSP has not been established. The investigators have quantified the concentration of HA in muscle using T1rho (T1ρ) MRI and found that T1ρ relaxation time is increased in post stroke shoulder pain and stiffness. Furthermore, dynamic US imaging using shear strain mapping can quantify dysfunctional gliding of muscle that may generate pain during ROM. Myofascial dysfunction can result in non-painful reduction in ROM (latent PSSP), which may become painful due to episodic overuse injury producing greater shear dysfunction (active PSSP). Hence, shear strain mapping may differentiate between latent versus active PSSP. Thus, quantitative Motor Recovery (MR) and US imaging may serve as useful biomarkers to elucidate the pathophysiology of myofascial dysfunction.

Conditions

Stroke

Outcome Measures

Primary Outcomes (1)

• T1ρ relaxation times (ms) in the treatment group

  Aim 1: T1ρ relaxation times in the treatment group. The primary endpoint will be change in T1ρ relaxation times on MRI in the shoulder girdle muscles of the paretic side between the baseline visit and 5-7 weeks post-first injection (i.e., post injection follow up at Visit 5/ end of Phase 1).

  Baseline, up to 7 weeks post first injection

Secondary Outcomes (6)

• Ultrasound shear strain

  7 weeks

• Pain rating as assessed by algometer

  7 weeks

• Pain free range of motion

  7 weeks

• Upper limb motion impairment as assessed by the Fugl-Meyer Scale

  7 weeks

• Upper limb function as assessed by Wolf Motor Function Test (time)

  7 weeks

Study Arms (2)

Hyaluronidase plus saline (Treatment Arm)

EXPERIMENTAL

hyaluronidase plus saline injection

Drug: hyaluronidase plus saline

Saline injection (Control Arm)

EXPERIMENTAL

normal saline injection

Drug: saline

Interventions

hyaluronidase plus saline DRUG

Injection of study drug with saline

Also known as: Treatment Arm

Hyaluronidase plus saline (Treatment Arm)

saline DRUG

injection of normal saline and no study drug

Also known as: Control Arm

Saline injection (Control Arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥18 years;
• hemiparesis from an ischemic or hemorrhagic stroke;
• time since cerebral injury 3-180 months prior;
• show a difference of more than 10 degrees of passive ER-ROM between non-paretic and paretic shoulders with or without pain
• ability to give informed consent and HIPAA authorization, and comply with study protocols;

You may not qualify if:

• treatment of spasticity with Botulinum toxin or intrathecal baclofen within the past three 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 positive depression screening on the Patient Health Questionnaire (PHQ)-9;
• pregnancy;
• known hypersensitivity to hyaluronidase;
• standard contraindications for MRI;
• have non-musculoskeletal PSSP such as only central pain or chronic regional pain syndrome (CRPS)
• any condition that will preclude the patient from completing the protocol as determined by the PI.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Stroke

Interventions

Hyaluronoglucosaminidase; Sodium Chloride

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Ning Cao, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ning Cao, MD

CONTACT

718-801-0026; ncao2@jhmi.edu

Preeti Raghavan

CONTACT

410-955-0703; praghavan@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: study because each participant will receive both Human Recombinant Hyaluronidase and the placebo at some point during the study. For example, if the participant is assigned to receive the study drug for the first set of injections, the participant will receive placebo for the second set of injections.

Study Record Dates

• First Submitted: November 22, 2024
• First Posted: December 5, 2024
• Study Start: March 28, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)