Hyaluronidase + CO2 Laser for Small Mouth

Recruiting at 1 trial location

Overseen By Sarah L Lonowski, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Nebraska

Disqualifiers: Pregnant, Infections, Prior treatment, others

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

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

Compensation: Varies

Number of Visits: 4

Duration: 12-24 weeks

3 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for scleroderma-induced microstomia, a condition that restricts mouth opening. The treatment uses a carbon dioxide (CO2) laser and hyaluronidase (a medication that breaks down certain tissues) to improve mouth movement, facilitating chewing, speaking, and oral hygiene. The goal is to enhance overall quality of life. People with scleroderma who struggle with mouth movement and receive treatment at specific clinics may be suitable for this study. Participants will undergo three laser sessions and a follow-up visit to assess the treatment's effectiveness. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it is important to discuss your medications with the trial team to ensure there are no interactions with the treatments.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have shown that injecting hyaluronidase just under the skin can help with conditions like microstomia, which causes difficulty in opening the mouth wide. Participants reported easier mouth opening and minimal discomfort. Research on CO2 lasers indicates they are effective and generally well-tolerated by patients when treating microstomia in systemic sclerosis, a disease affecting connective tissue. Most patients experienced improvements and tolerated the treatment well.

While the current findings are encouraging, please note that this trial is in an early stage. Researchers are still assessing the treatment's safety and effectiveness. Overall, using a CO2 laser with hyaluronidase appears promising, but further research is necessary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of hyaluronidase and CO2 laser for treating scleroderma-induced small mouth (microstomia) because it introduces a new method of delivery and a potential new approach to treatment. Unlike standard treatments that might involve physical therapy or surgery to address limited mouth opening, this approach uses a CO2 laser to assist in delivering hyaluronidase directly into the affected tissue. This method could enhance the penetration and effectiveness of the drug, potentially offering a safer, more tolerable, and less invasive option. By targeting the condition directly through the skin, this innovative technique could improve quality of life for patients more efficiently than existing treatments.

What evidence suggests that this trial's treatments could be effective for scleroderma-induced microstomia?

In this trial, participants will receive a combination of hyaluronidase and CO2 laser treatment to address microstomia. Research has shown that hyaluronidase may help treat microstomia, a condition where opening the mouth is difficult due to systemic sclerosis. Earlier studies demonstrated that patients could open their mouths wider, with some experiencing an improvement of about 4.1 mm, and they reported very few side effects.

Additionally, CO2 lasers have been found to help individuals with microstomia move their mouths more easily. Studies indicate that this laser treatment is effective and well-tolerated by patients. By combining hyaluronidase with CO2 laser treatment in this trial, the researchers aim to enhance these benefits, improving mouth movement and overall quality of life. ^{1 2 4 5 6}

Who Is on the Research Team?

Sarah L Lonowski, MD

Principal Investigator

University of Nebraska

Are You a Good Fit for This Trial?

This trial is for adults over 19 with scleroderma-induced microstomia, who are patients at specified clinics. They must be able to participate and have no severe dementia or seizure disorders. It excludes pregnant or breastfeeding women, those under 18, anyone cautious of hyaluronidase due to bee stings/bites, with infections near the treatment area, prior treatments like LADD or adverse reactions.

Inclusion Criteria

I have been diagnosed with a smaller mouth due to scleroderma.

I am willing and able to join the study.

I am 19 years old or older.

Exclusion Criteria

If you have been stung or bitten by a bee, hyaluronidase should be used carefully.

Pregnant and breastfeeding women

I have had treatments with hyaluronidase, LADD, CO2 laser, or had bad reactions to them.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo three separate laser sessions with intradermal hyaluronidase via laser-assisted drug delivery at 4 to 8-week intervals

12-24 weeks

3 visits (in-person)

Follow-up

Participants are monitored for sustained response and effectiveness three months after the last laser session

12 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CO2 Laser
• Hyaluronidase

Trial Overview The study tests a combination of CO2 laser therapy and intradermal hyaluronidase injections using Laser-assisted drug delivery (LADD) on people with small mouths from scleroderma. The goal is to improve mouth mobility and quality of life through three laser sessions followed by an evaluation after three months.

How Is the Trial Designed?

Group I: Ablative CO2 laser, and intradermal hyaluronidase, via laser-assisted drug delivery Experimental Treatment 2 Interventions

Uncover a safe, efficacious, and tolerable alternate treatment modality for scleroderma-induced microstomia. Evaluate disease severity and participant quality of life before and after alternative treatment.

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?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Published Research Related to This Trial

In a study involving 24 rats, recombinant human hyaluronidase (rHuPH20) was found to significantly reduce traumatic edema in rat paws more effectively than dexamethasone at multiple time points (3, 6, 12, 24, and 48 hours after induction).

The results suggest that rHuPH20 could be a promising alternative to dexamethasone for reducing edema, but further clinical studies are necessary to confirm its efficacy in postoperative settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Hyaluronidase Be an Alternative Postoperative Anti-edema Agent to Dexamethasone? Preliminary Results of an Animal Study. Koç, O., Er, N.[2023]

In a study of 100 patients undergoing simultaneous face lift and carbon dioxide laser resurfacing, the combination was found to be effective for cervicofacial rejuvenation, with only one case of significant skin necrosis observed.

While laser resurfacing over nonundermined skin did not increase postoperative complications, it was noted that applying laser treatment to undermined areas of the face lift flap raised the risk of skin necrosis, suggesting caution in such cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined cervicofacial rhytidectomy and laser skin resurfacing. Brackup, AB.[2019]

Hyaluronate lyase is a key enzyme in streptococcal bacteria that helps them spread through host tissues by degrading connective tissue components, which may also provide energy for the bacteria.

The enzyme was successfully expressed in E. coli and crystallized, allowing for detailed structural analysis with diffraction data collected to a resolution of 2.50 Å, which is crucial for understanding its mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crystallization and preliminary crystallographic analysis of recombinant hyaluronate lyase from Streptococcus suis. Khan, AH., Mohamed Omar, YM., Kakar, MA., et al.[2021]

The study successfully expressed and purified four types of human hyaluronidases (rHuHyal-1, -2, -3, and -4) from Nicotiana benthamiana, with rHuHyal-1 showing 2 to 6 times greater activity than the others at acidic pH, indicating its potential as a more effective therapeutic agent.

rHuHyal-1 demonstrated biochemical properties similar to the commercially available Hyal, PH-20, and was functionally active with glycosylation modifications, suggesting that plant-based production can yield effective enzymes comparable to those derived from animal sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of human hyaluronidase in a plant-derived protein expression system: plant-based transient production of active human hyaluronidase. Jung, Y., Jung, MY., Park, JH., et al.[2023]

In a study of 665 patients with various skin types, CO2 ablative and microfractionated laser treatments showed good results and acceptable complication rates, particularly for Fitzpatrick skin types III, IV, and V, which are common in the Latin population.

Satisfaction rates were high across all treatment groups, with 86.7% satisfaction in the mixed treatment group, indicating that combining treatment modalities can enhance patient outcomes and reduce complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laser Resurfacing for Latin Skins: The Experience with 665 Cases. Triana, L., Cuadros, SC., Triana, C., et al.[2021]

A purification method for dog submandibular-gland hyaluronidase was developed, achieving specific activities of up to 1.28 and 0.78 mumoles of N-acetylglucosamine per minute per mg of protein for non-sedimentable and sedimentable hyaluronidase, respectively.

The non-sedimentable and sedimentable hyaluronidase preparations showed similar properties, indicating they are closely related and resemble lysosomal hyaluronidase found in rat liver.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canine submandibular-gland hyaluronidase. Purification and properties. Tan, YH., Bowness, JM.[2019]

In a pilot study involving 15 healthy volunteers, lactated Ringer's (LR) solution was found to cause significantly less infusion-site discomfort compared to normal saline (NS), with average pain scores of 9.4 mm for LR versus 20.0 mm for NS on a 100-mm scale.

All participants preferred LR over NS for subcutaneous infusions, and while both solutions were generally well tolerated, the incidence of mild adverse events was higher with NS, suggesting LR may be a better option for rHuPH20-facilitated fluid administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the tolerability of recombinant human hyaluronidase + normal saline and recombinant human hyaluronidase + lactated ringer's solution administered subcutaneously: A phase IV, double-blind, randomized pilot study in healthy volunteers. Dychter, SS., Ebel, D., Mead, TR., et al.[2021]

The CO2 laser used in oral surgery has shown advantages over traditional electrosurgery, particularly in improving local control rates for malignant tumors.

Low-power laser treatment effectively desensitizes hypersensitive dentin and promotes wound healing by influencing collagenase activity, indicating its potential for pain relief and tissue recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications and basic studies of laser in dentistry and oral surgery. Nanami, T., Shiba, H., Ikeuchi, S., et al.[2008]

In a clinical trial involving 87 patients, treatment with 1072 nm infrared light therapy significantly reduced the healing time of herpes simplex labialis (HSL) lesions from a median of 177 hours in the placebo group to 129 hours in the treatment group.

The study demonstrated that while the infrared light therapy effectively sped up healing, it did not show a significant difference in the time to lesion crusting compared to the placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy of low-level light therapy using 1072 nm infrared light for the treatment of herpes simplex labialis. Dougal, G., Lee, SY.[2013]

Lasers have become essential tools in oral surgery and dentistry over the past 30 years, significantly enhancing diagnostic and therapeutic approaches for conditions like oral cancers, dental diseases, and pain syndromes.

The use of lasers in various treatments, including soft laser therapy and surgical applications, is revolutionizing oral healthcare, indicating that laser medicine may emerge as a distinct scientific field within stomatology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Laser in contemporary dentistry]. Gáspár, L.[2015]

A 43-year-old male was successfully treated for an extravasation mucocele caused by trauma from a maxillary canine, using a 940-nm diode laser for vaporization.

The treatment resulted in uneventful healing with no recurrence of the mucocele after 3 months, indicating the efficacy and safety of laser therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laser vaporization of extravasation type of mucocele of the lower lip with 940-nm diode laser. Agarwal, G., Mehra, A., Agarwal, A.[2015]

In a study of 373 CO₂ laser treatments on 287 patients, adverse events (AEs) occurred in 12.6% of treatments, with the most common being allergic dermatitis (4.6%) and acneiform breakouts (3.5%).

The risk of AEs increased significantly when multiple body areas were treated simultaneously, with 37.5% of patients experiencing AEs when three areas were treated, while subsequent treatments on the same area after healing showed no increased risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of fractionated carbon dioxide laser: review of 373 treatments. Campbell, TM., Goldman, MP.[2012]

In a study involving 10 subjects with photo-damaged skin, the nonsequential fractional CO2 laser resurfacing treatment showed significant clinical improvement without serious or long-term complications, indicating a favorable safety profile.

Histological and ultrastructural analyses revealed that the treatment promoted wound repair mechanisms and new collagen deposition, supporting its efficacy in enhancing skin appearance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective study of fractional scanned nonsequential carbon dioxide laser resurfacing: a clinical and histopathologic evaluation. Berlin, AL., Hussain, M., Phelps, R., et al.[2022]

In a study of 15 subjects treated with a novel fractional CO(2) laser device, 92% showed good to excellent improvement in photodamage, and 85% experienced significant reduction in facial wrinkles after 3 to 5 treatments at 3-week intervals.

The treatment was generally safe, with subjects reporting moderate discomfort (average score of 3.0 out of 5) and minimal downtime, as they resumed normal activities within 1-2 days after the procedure, while histological analysis confirmed new collagen formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a new fractional CO2 laser in the treatment of photodamage and acne scarring. Katz, B.[2022]

Lasers have been effectively used in dentistry since 1960 for various applications, including hard tissue procedures like cavity preparation and soft tissue treatments such as wound healing and removal of excess tissue.

Recent research highlights that lasers enhance the efficiency, specificity, and comfort of dental treatments, making them a valuable tool in modern dentistry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laser in dentistry: An innovative tool in modern dental practice. Verma, SK., Maheshwari, S., Singh, RK., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11500117/

Fractional Carbon Dioxide Laser for Treatment of ... This study aims to evaluate the benefits of CO2 laser resurfacing on microstomia and peri-oral rhytids in systemic sclerosis patients.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05995626?cond=Microstomia&viewType=Table&rank=2

Hyaluronidase Via LADD Scleroderma-induced Microstomia In this study, the investigator will combine two treatment modalities, ablative carbon dioxide (CO2) laser, and intradermal hyaluronidase, via laser-assisted ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4924459/

Improvement of Microstomia in Scleroderma after Carbon ... CO2 laser appears to be effective and well tolerated in the improvement of LMO in SS. Key Words: Systemic sclerosis, Microstomia, Limited mouth opening, Carbon ...

4. ctv.veeva.com ctv.veeva.com/study/hyaluronidase-via-ladd-scleroderma-induced-microstomia

Hyaluronidase Via LADD Scleroderma-induced Microstomia In this study, the investigator will combine two treatment modalities, ablative carbon dioxide (CO2) laser, and intradermal hyaluronidase, via ...

5. mjrheum.org mjrheum.org/assets/files/inpress/MJR%202023-0221_in%20press.pdf

Fractional Carbon Dioxide Laser for Treatment of ... This study aims to evaluate the benefits of CO2 laser resurfacing on microstomia and peri-oral rhyt- ids in systemic sclerosis patients. Method ...

6. researchgate.net researchgate.net/publication/361743987_Fractional_Ablative_Carbon_Dioxide_Lasers_for_the_Treatment_of_Morphea_A_Case_Series_and_Literature_Review

(PDF) Fractional Ablative Carbon Dioxide Lasers for the ... This study aims to evaluate the benefits of CO2 laser resurfacing on microstomia and peri-oral rhytids in systemic sclerosis patients.