Hyaluronidase for Muscle Spasms

Recruiting at 2 trial locations

Overseen By Robert Nickl, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Must not be taking: Botulinum toxin, Baclofen, Phenol, others

Disqualifiers: Parkinson's, ALS, MS, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 15 weeks

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests hyaluronidase injections to determine if they reduce muscle stiffness in the arm after a stroke. Participants will first receive either hyaluronidase or a saline solution and then switch to the other treatment, ensuring everyone tries the new treatment. The trial seeks individuals who experienced a stroke 4 to 180 months ago and have difficulty moving their shoulder, elbow, forearm, or wrist due to muscle stiffness. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

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 muscle stiffness recently or are adjusting anti-spastic medications.

Is there any evidence suggesting that hyaluronidase is likely to be safe for humans?

Research has shown that hyaluronidase is generally safe for people. This enzyme helps the body absorb injected fluids and medications more effectively. Studies have found that both young and older adults usually tolerate this treatment well. Common side effects might include mild swelling or pain at the injection site, but these are typically not serious. Serious side effects are rare, but they can include significant swelling in other parts of the body. Reporting any unusual symptoms to a doctor immediately is important. Overall, hyaluronidase is considered safe when used correctly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for muscle spasms, such as muscle relaxants and physical therapy, hyaluronidase is unique because it works by breaking down hyaluronic acid, which can improve tissue permeability and ease muscle stiffness and spasms. This mechanism offers a fresh approach by potentially enhancing mobility and comfort in a way that traditional muscle relaxants might not. Researchers are excited about hyaluronidase because it promises faster relief and targets the underlying tissue environment, rather than just the symptoms of spasms.

What evidence suggests that hyaluronidase might be an effective treatment for muscle spasms?

Research has shown that hyaluronidase can reduce muscle stiffness and improve joint movement. In earlier studies, patients who received hyaluronidase injections experienced better movement and less muscle tightness. This trial will evaluate hyaluronidase, administered alongside saline to participants in the treatment arm, to assess its effectiveness in treating muscle stiffness after a stroke. The enzyme breaks down certain substances in the body, enhancing the effectiveness of other treatments and maintaining tissue hydration. Early results are promising, suggesting it could serve as a new therapy for easing muscle spasms. ^{6 7 8 9 10}

Who Is on the Research Team?

Ning Cao, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for individuals who had a stroke 6-120 months ago and are experiencing moderate to severe muscle stiffness in their upper limb. They must be able to consent, undergo MRI scans, and follow the study's procedures. Excluded are those with recent spasticity treatments, other neurological conditions like Parkinson's or ALS, significant cognitive issues or depression, pregnancy, hyaluronidase allergy, claustrophobia or MRI contraindications.

Inclusion Criteria

I had a stroke between 4 months and 15 years ago.

I experience significant muscle stiffness.

Willingness to have MRI, complete all clinical assessments, and comply with study protocols

Exclusion Criteria

Clinically significant cognitive dysfunction with score <19 on Folstein's Mini Mental Status Examination or depression with score >10 on the PHQ-9

I've had treatments for muscle stiffness in the last year.

Any condition that will preclude the patient from completing the protocol as determined by the PI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hyaluronidase or saline injections to test effects on muscle stiffness and spasticity

15 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hyaluronidase

Trial Overview The trial tests human recombinant hyaluronidase injections against saline (placebo) in reducing muscle stiffness post-stroke. It's double-blind and placebo-controlled with two phases ensuring all participants receive treatment at some point over nine weeks with seven visits including MRIs before the first injection but not after the second.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

Hyaluronidase plus saline

Group II: Control Arm Placebo Group 1 Intervention

Normal Saline

Hyaluronidase is already approved in United States, European Union for the following indications:

Approved in United States as Human Recombinant Hyaluronidase for:

• Subcutaneous urography
• Extravasation of contrast agents
• Off-label use for muscle stiffness and spasticity

Approved in European Union as Hyalase for:

• Subcutaneous urography
• Extravasation of contrast agents
• Off-label use for muscle stiffness and spasticity

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Sheikh Khalifa Stroke Institute

Collaborator

Trials

3

Recruited

220+

Published Research Related to This Trial

Hirayama disease is a rare condition that causes weakness in the upper extremities due to abnormal positioning of the cervical spinal cord, as seen in a 15-year-old male with progressive right arm weakness.

Diagnosis requires careful imaging, particularly with the neck in a flexed position, since standard neutral position imaging may not reveal the disorder, leading to potential misdiagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hirayama Disease: A 15-Year-Old Male With Progressive Distal Right Upper Extremity Weakness. Gritsch, D., Mbonde, AA., Khoury, J.[2023]

In a study involving rabbit eyes, injections of Wydase (bovine testicular hyaluronidase) at doses of 50 IU and above caused significant corneal toxicity, including persistent edema and endothelial necrosis.

In contrast, the Sigma preparation of hyaluronidase showed only transient local toxicity, suggesting that the impurities in Wydase and its thimerosal-containing vehicle may contribute to its harmful effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corneal toxicity of intraocular hyaluronidase. Jumper, JM., McCauley, MB., Equi, RA., et al.[2003]

A 41-year-old woman experienced a focal erythematous plaque at the site of a hyaluronidase injection used to correct excess hyaluronic acid filler, indicating a potential allergic reaction.

While hyaluronidase is generally considered safe for correcting HA fillers, this case highlights that allergic reactions, although uncommon, should be considered when patients present with localized skin reactions after injection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergic reaction to hyaluronidase use after hyaluronic acid filler injection. Kim, MS., Youn, S., Na, CH., et al.[2015]

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]

In a study involving 32 hospice patients over 6 months, recombinant human hyaluronidase (rHuPH20) was effectively used to enhance subcutaneous hydration and drug infusion, allowing flow rates up to 500 mL/hr without significant adverse events.

The treatment facilitated hydration for symptom control in 26 patients and improved the delivery of medications in 6 patients, indicating its potential for broader use in both inpatient and outpatient settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experiences with subcutaneous recombinant human hyaluronidase. Pirrello, RD., Ting Chen, C., Thomas, SH.[2022]

Patients with Hirayama disease (HD) showed significantly lower cross-sectional areas (CSAs) of cervical spine muscles compared to healthy individuals, indicating muscle weakness that may contribute to cervical spine instability.

The study found a mismatch in the CSA ratios of superficial flexors and extensors in HD patients, suggesting an imbalance in muscle strength that could further compromise cervical spine stability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there cervical spine muscle weakness in patients with Hirayama disease? A morphological study about cross-sectional areas of muscles on MRI. Li, Z., Zhang, W., Wu, W., et al.[2021]

Intramuscular injections of hyaluronidase, an enzyme that breaks down hyaluronan, have been shown to effectively reduce muscle stiffness and improve range of motion in patients with spasticity.

These findings support the hyaluronan hypothesis, suggesting that targeting hyaluronan accumulation could be a promising therapeutic approach for managing muscle stiffness following central nervous system injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Therapies for Spastic Movement Disorders. Raghavan, P.[2020]

A novel recombinant hyaluronidase was developed that matches the catalytic activity of existing commercial bovine-derived enzymes, which can enhance drug transport by breaking down hyaluronan barriers.

The new enzyme features a simplified purification process using Ni2+ affinity chromatography, making it easier to produce and potentially safer for clinical use, as it avoids risks associated with bovine-derived products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a New Type of Recombinant Hyaluronidase Using a Hexahistidine; Possibilities and Challenges in Commercialization. Park, C., Song, YK., Kim, YH., et al.[2019]

Hirayama disease (HD) is a rare and benign motor neuron disorder that primarily affects the C7-T1 myotomes, leading to muscle atrophy and weakness in the upper extremities, as demonstrated in a case of a 23-year-old male with significant symptoms.

The diagnosis of HD can be confirmed through clinical evaluation and specific MRI features, indicating that it should be treated conservatively rather than surgically, as unnecessary surgical interventions were performed in this case before the correct diagnosis was established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hirayama disease - Early MRI diagnosis of subacute medullary ischemia: A case report. Galletta, K., Gaeta, M., Alafaci, C., et al.[2022]

Hirayama's disease (HD) is a rare, self-limited motor neuron disease characterized by asymmetric weakness and atrophy in the upper extremities, with initial symptoms often including hand weakness and tremors; the study involved eight Italian patients evaluated through clinical assessments and advanced imaging techniques.

MRI is crucial for diagnosing HD, as it can confirm clinical suspicions and rule out other conditions; the study proposes a standardized MRI protocol that includes both neutral and flexed positions to enhance diagnostic accuracy and patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hirayama's disease: an Italian single center experience and review of the literature. Vitale, V., Caranci, F., Pisciotta, C., et al.[2020]

In a study of 61 patients with severe low back pain and sciatica, the combination of hyaluronidase and triamcinolone in lumbar interlaminar epidural injection (LIEI) showed greater pain relief after 8 weeks compared to either treatment alone.

Specifically, 70.4% of patients receiving the combination treatment reported pain improvement, while only 44.4% and 31.3% improved in the triamcinolone and hyaluronidase-only groups, respectively, with significant improvement in disability scores observed only in the combination group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The additional effect of hyaluronidase in lumbar interlaminar epidural injection. Kim, SB., Lee, KW., Lee, JH., et al.[2021]

A recombinant hyaluronidase (rTsHyal-1) was successfully produced from Tityus serrulatus scorpion venom using the Pichia pastoris system, yielding 0.266 mg/mL of the enzyme, which is significant for further studies due to its previously low availability.

rTsHyal-1 demonstrated high substrate specificity for hyaluronan and optimal activity at pH 6.0 and 40 °C, indicating its potential applications in medicine and aesthetics, while also being the first of its kind expressed in this system with preserved activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterologous expression of rTsHyal-1: the first recombinant hyaluronidase of scorpion venom produced in Pichia pastoris system. Amorim, FG., Boldrini-França, J., de Castro Figueiredo Bordon, K., et al.[2022]

Hylenex recombinant, a new formulation of human hyaluronidase, has been shown to be safe and well tolerated in a study with 100 volunteers, with no allergic reactions reported after intradermal injections.

This recombinant version is expected to have lower allergic and immunological risks compared to traditional animal-derived hyaluronidases, supporting its approval by the US Food and Drug Administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment and implication of the allergic sensitivity to a single dose of recombinant human hyaluronidase injection: a double-blind, placebo-controlled clinical trial. Yocum, RC., Kennard, D., Heiner, LS.[2007]

In a study involving 21 rabbits and 40 rats, antibodies against hyaluronidase were detected after subcutaneous and intramuscular applications, indicating a potential for immunogenicity, especially with these methods of administration.

While 26% of human patients developed antibodies after receiving hyaluronidase, no anaphylactic reactions were observed in patients who continued treatment, suggesting that while anaphylaxis is a rare risk, it remains a possibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Animal experimental studies on immunogenicity, humoral response and danger of anaphylaxis in parenteral administration of hyaluronidase]. Storch, H., Dellas, T., Bellmann, H.[2009]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4972484/

Human Recombinant Hyaluronidase Injections For Upper ... In this case series, we report that intramuscular injections of the enzyme hyaluronidase increased passive and active joint movement and reduced muscle ...

2. hopkinsmedicine.org hopkinsmedicine.org/clinical-trials/results/irb00273264

Peripheral Modulation of Muscle Stiffness and Spasticity This is a single-center, double-blind, randomized, placebo-controlled, sequential Phase II trial of human recombinant hyaluronidase injections in individuals ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6333099/

Emerging Therapies for Spastic Movement Disorder - PMC These results provide preliminary evidence of the hyaluronan hypothesis and suggest an emerging therapy to reduce muscle stiffness using the enzyme ...

4. withpower.com withpower.com/trial/phase-3-muscle-spasticity-9-2021-29894

Hyaluronidase for Muscle Spasms Research shows that hyaluronidase is effective in facilitating drug absorption and hydration in medical settings, which suggests it may help in conditions ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01020513?term=AREA%5BBasicSearch%5D(Hyaluronidase%20(Human%20Recombinant))&rank=4

Subcutaneous Recombinant Human Hyaluronidase ... This is an observational study examining the workflow dynamics and training requirements that support effective use of subcutaneous ...

6. go.drugbank.com go.drugbank.com/drugs/DB06205

Hyaluronidase (human recombinant) Hyaluronidase is an enzyme used to improve the absorption and dispersion of parenterally administered fluids, drugs, and contrast agents.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK545163/

Hyaluronidase - StatPearls - NCBI Bookshelf - NIH Hyaluronidase is an enzyme useful in facilitating the management of injectable medications. This activity reviews the indications, action, adverse effects, ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/021859s005lbl.pdf

HYLENEX recombinant (hyaluronidase human injection) No overall differences in safety or effectiveness have been observed between elderly and younger adult patients. ADVERSE REACTIONS. The most frequently reported ...

9. drugs.com drugs.com/mtm/hyaluronidase-injection.html

Hyaluronidase injection Uses, Side Effects & Warnings Hyaluronidase may cause serious side effects. Call your doctor at once if you have: swelling in your hands, feet, or other body areas; or. pain, ...

10. tandfonline.com tandfonline.com/doi/full/10.1080/17425247.2021.1981286

Safety of recombinant human hyaluronidase PH20 for ... The immunogenicity profile demonstrates no adverse effects associated with treatment-emergent rHuPH20 antibody responses. Immunogenicity to monoclonal ...