StrokePhase 2NCT06718413
Myofascial Dysfunction in Post Stroke Shoulder Pain
A Phase 2 study testing hyaluronidase plus saline and saline in people with Stroke, run by Johns Hopkins University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- hyaluronidase plus saline and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2025to 31 Aug 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
Preeti Raghavan, MD, 917-488-9263
Ning Cao, MD, 718-801-0026
About this study
Official title: Quantifying and Treating Myofascial Dysfunction in Post Stroke Shoulder Pain
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.
Read the 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
- Being tested
- hyaluronidase plus saline, saline
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hyaluronidase plus salineDrug
Also called Treatment Arm
Injection of study drug with saline
salineDrug
Also called Control Arm
injection of normal saline and no study drug
| Study group | Role | What they receive |
|---|---|---|
| Hyaluronidase plus saline (Treatment Arm) | Experimental | hyaluronidase plus saline injection Receives: Drug: hyaluronidase plus saline |
| Saline injection (Control Arm) | Experimental | normal saline injection Receives: Drug: saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline, up to 7 weeks post first injection
Secondary outcomes (6)
Ultrasound shear strain
Percent shear strain obtained via ultrasound in the two groups. Higher shear strain is better.
Measured: 7 weeks
Pain rating as assessed by algometer
Pain rating on quantitative sensory testing of shoulder muscles. Lower pain rating is better.
Measured: 7 weeks
Pain free range of motion
Range of motion for the most affected shoulder movement. Higher range of motion is better.
Measured: 7 weeks
Upper limb motion impairment as assessed by the Fugl-Meyer Scale
Upper limb Fugl-Meyer scale; score range 0-66 with higher numbers reflecting less arm impairment
Measured: 7 weeks
Upper limb function as assessed by Wolf Motor Function Test (time)
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.
Measured: 7 weeks
Quality of life as assessed by the Stroke Impact Scale
Scores range from 0-100, with higher score showing better quality of life and lower stroke impact.
Measured: 7 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2024
- Study start28 Mar 2025
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Sponsor
- Investigators
- Ning Cao, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06718413
- Sponsor's protocol ID
- IRB00354872
- Other IDs
- 4R33AT012279-02
- Status last verified
- Oct 2026
- First submitted
- 22 Nov 2024
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantifying and Treating Myofascial Dysfunction in Post Stroke Shoulder Pain
- ClinicalTrials.gov ID
- NCT06718413
- Acronym / sponsor ID
- IRB00354872
- Conditions
- Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 68 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 28 Mar 2025 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 31 Aug 2028 (estimated)
- First posted
- 5 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Hyaluronidase plus saline (Treatment Arm) | Experimental | Drug: hyaluronidase plus salinehyaluronidase plus saline injection |
| Saline injection (Control Arm) | Experimental | Drug: salinenormal saline injection |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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;
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hyaluronidase plus salineAlso: Treatment ArmInjection of study drug with saline | Drug | Hyaluronidase plus saline (Treatment Arm) |
| salineAlso: Control Arminjection of normal saline and no study drug | Drug | Saline injection (Control Arm) |
Primary outcome
T1ρ relaxation times (ms) in the treatment group
Time frame: 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).
6 secondary outcomes
Ultrasound shear strain
Time frame: 7 weeks
Pain rating as assessed by algometer
Time frame: 7 weeks
Pain free range of motion
Time frame: 7 weeks
Upper limb motion impairment as assessed by the Fugl-Meyer Scale
Time frame: 7 weeks
Upper limb function as assessed by Wolf Motor Function Test (time)
Time frame: 7 weeks
Quality of life as assessed by the Stroke Impact Scale
Time frame: 7 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ning Cao, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing hyaluronidase plus saline and saline in people with Stroke, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ning Cao, MD (718-801-0026, ncao2@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
T1ρ relaxation times (ms) in the treatment group (time frame: Baseline, up to 7 weeks post first injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.