Myofascial Dysfunction in Post Stroke Shoulder Pain

Phase 2

Recruiting

• Conditions: Stroke
• Interventions: Drug: hyaluronidase plus saline; Drug: saline

• Registration Number: NCT06718413
• Lead Sponsor: Johns Hopkins University

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.

Detailed Description

Aim 1: Quantify the extent of HA accumulation in shoulder muscles using T1rho MRI before and after treatment with hyaluronidase injections versus placebo in patients with PSSP. Hypothesis: The primary objective will be to demonstrate that dysfunctional shoulder girdle muscles on the paretic side in patients with PSSP will show decreased T1ρ relaxation times in the infraspinatus muscle after treatment with hyaluronidase injections compared with placebo 5-7 weeks post-injection.

Aim 2. Determine maximum sheer strain in shoulder muscles using US shear strain mapping before and after treatment with hyaluronidase injections versus placebo in patients with PSSP. Research Hypothesis: Shear strain on the paretic side in patients with PSSP measured using ultrasound shear mobility between the pectoralis major and minor muscles will decrease after treatment with hyaluronidase injections compared with placebo 5-7 weeks post-injection.

Aim 3. Assess the impact of hyaluronidase injections compared with placebo on shoulder pain, pain free range of motion, upper limb motor impairment, function and quality of life in patients with PSSP. Hypothesis: Hyaluronidase injections compared with placebo in patients with PSSP will lead to (1) reduced pain as assessed using the pain questionnaires and lower pain-pressure thresholds with quantitative sensory testing using an algometer; (2) increased pain free range of motion in most affected shoulder joints; (3) reduced upper limb motor impairment measured using the Fugl-Meyer Scale; (4) increased function measured using the Wolf Motor Function Test; and (5) improved quality of life measured using the Stroke Specific Quality of Life scale.

Study Timeline

• Study First Submitted: 2024-11-22
• Study First Submitted QC: 2024-12-04
• Study First Posted: 2024-12-05
• Status Verified: 2025-03
• Study Start: 2025-03-28
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-03
• Primary Completion: 2027-08-31
• Study Completion: 2028-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

• 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;

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Hyaluronidase plus saline (Treatment Arm)	hyaluronidase plus saline	hyaluronidase plus saline injection
Saline injection (Control Arm)	saline	normal saline injection

Primary Outcome Measures

Name	Time	Method
T1ρ relaxation times (ms) in the treatment group	Baseline, up to 7 weeks post first injection	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).

Secondary Outcome Measures

Name	Time	Method
Quality of life as assessed by the Stroke Impact Scale	7 weeks	Scores range from 0-100, with higher score showing better quality of life and lower stroke impact.
Ultrasound shear strain	7 weeks	Percent shear strain obtained via ultrasound in the two groups. Higher shear strain is better.
Pain rating as assessed by algometer	7 weeks	Pain rating on quantitative sensory testing of shoulder muscles. Lower pain rating is better.
Pain free range of motion	7 weeks	Range of motion for the most affected shoulder movement. Higher range of motion is better.
Upper limb motion impairment as assessed by the Fugl-Meyer Scale	7 weeks	Upper limb Fugl-Meyer scale; score range 0-66 with higher numbers reflecting less arm impairment
Upper limb function as assessed by Wolf Motor Function Test (time)	7 weeks	Participants are given a battery of functional tasks that are timed and scored on movement quality. Score range is 0-120, lower scores being better.

Trial Locations

Locations (1)

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States