Myofascial Dysfunction in Post Stroke Shoulder Pain

NCT ID: NCT06718413

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-28
• Study Completion Date: 2028-08-31

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.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Hyaluronidase plus saline (Treatment Arm)

hyaluronidase plus saline injection

Group Type: EXPERIMENTAL

hyaluronidase plus saline

Intervention Type: DRUG

Injection of study drug with saline

Saline injection (Control Arm)

normal saline injection

Group Type: EXPERIMENTAL

saline

Intervention Type: DRUG

injection of normal saline and no study drug

Interventions

hyaluronidase plus saline

Injection of study drug with saline

Intervention Type: DRUG

saline

injection of normal saline and no study drug

Intervention Type: DRUG

Other Intervention Names

Treatment Arm; Control Arm

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ning Cao, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ning Cao, MD

Role: CONTACT

ncao2@jhmi.edu

718-801-0026

Preeti Raghavan

Role: CONTACT

praghavan@jhmi.edu

410-955-0703

Facility Contacts

Preeti Raghavan, MD

Role: primary

917-488-9263

Ning Cao, MD

Role: backup

718-801-0026

Other Identifiers

4R33AT012279-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00354872

Identifier Type: -

Identifier Source: org_study_id