Clinical trial NCT06718413: Myofascial Dysfunction in Post Stroke Shoulder Pain
Official title: Quantifying and Treating Myofascial Dysfunction in Post Stroke Shoulder Pain
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Stroke
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2024-12-05
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: T1ρ relaxation times (ms) in the treatment group
timeFrame: Baseline, up to 7 weeks post first injection
Secondary outcomes:
measure: Ultrasound shear strain
timeFrame: 7 weeks
measure: Pain rating as assessed by algometer
timeFrame: 7 weeks
measure: Pain free range of motion
timeFrame: 7 weeks
measure: Upper limb motion impairment as assessed by the Fugl-Meyer Scale
timeFrame: 7 weeks
measure: Upper limb function as assessed by Wolf Motor Function Test (time)
timeFrame: 7 weeks
measure: Quality of life as assessed by the Stroke Impact Scale
timeFrame: 7 weeks
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Ning Cao, MD
role: PRINCIPAL_INVESTIGATOR
References: