Recruiting
Phase 2

Observational Study

Sponsor:

Johns Hopkins University

Code:

NCT06718413

Conditions

Stroke

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

hyaluronidase plus saline

saline

Study Details

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

Study ID

NCT06718413

Start date

Mar 28, 2025

Status verified date

Feb, 2026

Completion date

Aug 31, 2028

Anticipated

Primary completion date

Aug 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Enrollment

68 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Hyaluronidase plus saline (Treatment Arm)

hyaluronidase plus saline injection

experimental: Saline injection (Control Arm)

normal saline injection

Interventions

hyaluronidase plus saline

Injection of study drug with saline

saline

injection of normal saline and no study drug

Primary outcome measure

  • T1ρ relaxation times (ms) in the treatment group [ Time Frame: Baseline, up to 7 weeks post first injection ]

Central Contacts and Locations

Central contacts

Ning Cao, MD

718-801-0026ncao2@jhmi.edu

Preeti Raghavan

410-955-0703praghavan@jhmi.edu

Locations

Johns Hopkins University

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Preeti Raghavan, MD

917-488-9263

Ning Cao, MD

718-801-0026

More Information

Sponsor

Johns Hopkins University

Last update posted

Feb 27, 2026

Last verified

Feb, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-02-27.