Hyaluronidase for Stroke-Related Shoulder Pain

Overseen By Preeti Raghavan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Botulinum toxin, Baclofen, Phenol

Disqualifiers: Parkinson's, ALS, MS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 5-7 weeks

68 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have had certain treatments for spasticity recently or are adjusting anti-spastic medications.

What data supports the effectiveness of the treatment hyaluronidase for stroke-related shoulder pain?

Research shows that hyaluronic acid, a component related to hyaluronidase, can help reduce shoulder pain and improve movement in stroke patients. Additionally, hyaluronidase has been shown to enhance the effects of other treatments for shoulder disorders, suggesting it may be beneficial for stroke-related shoulder pain. ^{1 2 3 4 5}

Is hyaluronidase safe for treating shoulder pain?

Research on hyaluronic acid, which is similar to hyaluronidase, shows it is generally safe for treating shoulder pain, with studies focusing on its use for shoulder injuries and pain relief in stroke patients. ^{1 2 3 4 6}

How is the drug hyaluronidase different from other treatments for stroke-related shoulder pain?

Hyaluronidase is unique because it is an enzyme that breaks down hyaluronic acid, potentially enhancing the effects of other treatments by improving tissue permeability. This is different from standard treatments that may not focus on altering tissue properties to enhance drug delivery. ^{1 2 3 5 7}

Research Team

Ning Cao, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 who have had a stroke between 3 to 180 months ago, leading to hemiparesis (weakness on one side of the body). They must be able to consent and follow study rules. Eligible participants show at least a 10-degree difference in shoulder movement range between their affected and unaffected sides, with or without pain.

Inclusion Criteria

I am 18 years old or older.

I have weakness on one side of my body due to a stroke.

I had a brain injury between 3 to 180 months ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive hyaluronidase or saline injections to treat post-stroke shoulder pain

5-7 weeks

5 visits (in-person)

Follow-up

Participants are monitored for changes in T1ρ relaxation times, pain, range of motion, and quality of life

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• hyaluronidase

Trial Overview The trial is testing whether injecting hyaluronidase mixed with saline into the shoulder can help relieve pain better than saline alone. This study aims to see if breaking down hyaluronic acid buildup improves muscle function and reduces pain in post-stroke patients.

Participant Groups

Group I: Saline injection (Control Arm) Experimental Treatment 1 Intervention

normal saline injection

Group II: Hyaluronidase plus saline (Treatment Arm) Experimental Treatment 1 Intervention

hyaluronidase plus saline injection

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Findings from Research

Intra-articular injection of hyaluronic acid (HA) significantly reduces pain and improves function in patients with rotator cuff tears, based on a systematic review of 11 studies involving 1102 patients.

The review found no severe adverse reactions associated with HA injections, indicating that it is a safe treatment option compared to corticosteroid injections and other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid. Osti, L., Buda, M., Buono, AD., et al.[2022]

Hyaluronidase, an enzyme that breaks down hyaluronic acid, has shown to be well-tolerated in the human central nervous system and rabbit eyes, suggesting a potential for safe use in neurological conditions.

In three patients with hydrocephalus and related conditions, intraventricular injections of hyaluronidase effectively managed symptoms, delayed the need for shunting, and prevented fluid reaccumulation, indicating its potential therapeutic efficacy in central nervous system disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of hyaluronidase in the central nervous system. Gegalian, L.[2004]

References

1. United States pubmed.ncbi.nlm.nih.gov

The long-term effects of hyaluronic acid on hemiplegic shoulder pain and injury in stroke patients: A randomized controlled study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

The effects of hyaluronic acid on hemiplegic shoulder injury and pain in patients with subacute stroke: A randomized controlled pilot study. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Effect of Intra-articular Hyaluronic Acid Injection on Hemiplegic Shoulder Pain After Stroke. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Therapeutic effects of hyaluronate injections in patients with chronic painful shoulder: a meta-analysis of randomized controlled trials. [2011]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

The additive effects of hyaluronidase in subacromial bursa injections administered to patients with peri-articular shoulder disorder. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Use of hyaluronidase in the central nervous system. [2004]