A Clinical Study of Freshly Manufactured 35kDa Hyaluronan Fragment in the Treatment of Pain

Study Overview
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Brief Summary
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Local used high molecular weight Hyaluronan (HA) with high viscosity has a variety of receptors in the human body, including CD44, LYVE-1, RHAMM, HARE, Siglec-9, TLR2, CEMIP and TMEM2. Intra-articular local injection of HA has a certain degree of analgesic effect. Local injection of HA into the nerve trunk directed by ultrasound was used for the treatment of neuropathic pain. It was reported that the analgesic effect of HA is regulated by TRPV1 ion channels. This study hypothesizes that hyaluronidase cleaves HA to generate low molecular weight HA fragments HA35 with good tissue permeability, which may bind to a variety of HA receptors on the cell surface within the tissues and produce a broad-spectrum analgesic effect. In this study, 35kDa Hyaluronan fragment HA35 was prepared by mixing hyaluronidase PH20 injection and high molecular weight Hyaluronan (HA) injection at room temperature for 20 minutes. In this study, hyaluronidase injection and Hyaluronan injection were off-label used to conduct an investigator-initiated study (IIT or IIS) for the treatment of herpes zoster and shoulder, neck, back and temporal pain.

Detailed Description
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Bioactive Hyaluronan fragment HA35 of 35kDa was isolated from human colostrum. Literature studies have shown that female breast hyaluronidase and male testicular sperm acrosomal hyaluronidase PH20 come from the same gene. The investigators, recombinant human hyaluronidase PH20 and neutral hyaluronidase (PH20 or SPAM1) of bovine testicular sperm acrosome were used to cleave macromolecular Hyaluronan. Regardless of the cutting time, the Hyaluronan fragment HA35 with an average molecular weight 35kDa was produced(Registration number L20200708MP07707, Ministry of Health, Mongolia). Hyaluronidase injection is often used to improve the penetration and absorption of other injectable drugs. Hyaluronidase injection is also used to degrade excessive use of cosmetic injection or improper use of cross-linked macromolecular Hyaluronan fillers, which is an off-label drug use of hyaluronidase（https://www.realself.com/news/ hyaluronidase-dissolve-fillers）. In this study, Hyaluronan fragment HA35 of 35kDa was prepared by mixing hyaluronidase injection extracted from bovine testis (hyaluronidase for injection, H31022111) and Hyaluronan injection (sodium hyaluronate injection, H20174089) at room temperature for 20 minutes. Its analgesic effect on herpes zoster, shoulder, neck, back, and temporal pain was studied. In this study, off-label drug use of hyaluronidase injection and Hyaluronan injection （https://www.realself.com/news/ hyaluronidase-dissolve-fillers）were used in the clinical study of shoulder, neck, back and temporal pain and herpes zoster pain, namely investigator initiated trails. In this clinical trial, 26 patients with shoulder, neck, back and temporal pain were studied in the Department of pain diagnosis and treatment of the affiliated Hospital of Qingdao University. Ten patients with herpes zoster were treated in the pain Department of the affiliated Hospital of Qingdao University. According to the ratio of 100mg high molecular Hyaluronan / 2000 unit hyaluronidase, the high molecular Hyaluronan injection (sodium hyaluronate injection, H20174089) and the hyaluronidase injection extracted from bovine testis (hyaluronidase for injection) were mixed at room temperature for 20 minutes. Each time according to the amount of high molecular Hyaluronan containing 100 mg Hyaluronan and hyaluronidase mixture, pain point area and pain point area of the nerve trunk innervation of the local multi-point injection. Then, pain scale was used to evaluate and record the pain relief of patients before and after treatment.

Official Title
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A Preliminary Clinical Study of Freshly Manufactured 35kDa Hyaluronan Fragment in the Treatment of Herpes Zoster Pain and Shoulder, Neck, Back and Temporal Pain

Conditions
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Shoulder Pain, Neck Pain, Back Pain, Temporal Pain, Herpes Zoster Pain

Intervention / Treatment
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* Drug: HA35(L20200708MP07707, Ministry of Health, Mongolia) was freshly manufactured by mixing hyaluronidase PH20 injectable solution (H31022111) and high-molecular-weight HA injectable solution (H20174089)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Shoulder, neck, back and temporal pain. The course of the disease ranged from 0 to 8 months. Herpes zoster pain. The course of 0-2 months. Exclusion Criteria: Individuals with severe spinal pathology (including fractures, inflammatory diseases and tumors)

Ages Eligible for Study
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Minimum Age: 39 Years
Maximum Age: 63 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A self-controlled an open label clinical study(An investigator-initiated off-label use clinical study)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 35kDa hyaluronan fragment HA35 injection<br>100 mg Hyaluronan is locally injected at the pain point or where the nerve trunk is innervated by the pain point. | Drug: HA35(L20200708MP07707, Ministry of Health, Mongolia) was freshly manufactured by mixing hyaluronidase PH20 injectable solution (H31022111) and high-molecular-weight HA injectable solution (H20174089)<br>* This group will inject once a week. Evaluation of pain score after 30 seconds and 3 hours.<br>* Other names: HA35;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores of all shoulder, neck, back, temporal and herpes zoster pain | The pain scale is a tool that doctors use to help assess patients' pain. Each patient rated their pain on a scale of 0 to 10. 0 means no pain and 10 means the most painful. Statistical t-test was used to calculate and evaluate the pain intensity, which was expressed as mean ±standard deviation. | 3 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hyaluronidase, Hyaluronan, 35kDa Hyaluronan fragment, pain caused by herpes zoster, pain caused by shoulder neck back and temporal