Hyaluronidase + CO2 Laser for Small Mouth

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Sarah L Lonowski, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Nebraska

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Two treatment methods, ablative carbon dioxide (CO2) laser and intradermal hyaluronidase, will be combined to maximize the beneficial potential of each. Laser-assisted drug delivery (LADD) has been shown to be effective for the administration of medications in diverse skin diseases but not previously reported for the treatment of scleroderma-induced microstomia. By using this laser technique, the investigator can reduce the pain of typical hyaluronidase injections and reap the therapeutic benefit of the laser treatment itself. The investigator's goal is to create greater mouth mobility for chewing and speaking as well as improved oral hygiene, self-esteem, and overall quality of life. Each participant will undergo three separate laser sessions at 4 to 8-week intervals. Participants will also complete a follow-up visit three months after the last laser session to evaluate the response.

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.

What data supports the idea that Hyaluronidase + CO2 Laser for Small Mouth is an effective treatment?

The available research shows that lasers, including CO2 lasers, have been effective in various dental and oral surgery applications. They have been used to improve healing, reduce pain, and treat conditions like hypersensitive teeth and oral mucosa diseases. Although the specific combination of Hyaluronidase and CO2 Laser for Small Mouth isn't directly mentioned, the general effectiveness of lasers in oral treatments suggests potential benefits. Compared to other treatments, lasers are noted for increasing efficiency, comfort, and specificity in dental procedures. ^{1 2 3 4 5}

What safety data is available for Hyaluronidase + CO2 Laser treatment?

The safety data for CO2 laser treatments, including fractional CO2 lasers, indicates a high risk:benefit ratio with a notable frequency of adverse events. Studies have shown that CO2 laser resurfacing can lead to complications, especially in certain skin types (Fitzpatrick III, IV, and V). However, newer fractional CO2 laser devices have demonstrated significant improvements in facial conditions with manageable side effects like erythema lasting 2-3 days. There is no specific safety data available for the combination of Hyaluronidase and CO2 laser, but the individual components have been studied separately. ^{6 7 8 9 10}

Is the drug Hyaluronidase a promising treatment for small mouth?

Yes, Hyaluronidase is a promising treatment because it helps improve the absorption of medicines and has anti-inflammatory and anti-swelling effects, which can be beneficial in treating small mouth. ^{11 12 13 14 15}

Research Team

Sarah L Lonowski, MD

Principal Investigator

University of Nebraska

Eligibility Criteria

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 an infection or inflammation near my treatment area.

Treatment Details

Interventions

• CO2 Laser (Procedure)
• Hyaluronidase (Enzyme)

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.

Participant Groups

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 patients with scleroderma-induced microstomia. Evaluate disease severity and patient quality of life before and after alternative treatment is administered

Who Is Running the Clinical Trial?

University of Nebraska

Lead Sponsor

Trials

563

Recruited

1,147,000+

Michael Dixon

University of Nebraska

Chief Executive Officer since 2010

PhD in Molecular Biology

Dr. Makker

University of Nebraska

Chief Medical Officer since 2020

MD from University of Nebraska Medical School

Findings from Research

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]

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 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 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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Clinical applications and basic studies of laser in dentistry and oral surgery. [2008]

2. India pubmed.ncbi.nlm.nih.gov

Laser vaporization of extravasation type of mucocele of the lower lip with 940-nm diode laser. [2015]

3. England 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. [2013]

4. India pubmed.ncbi.nlm.nih.gov

Laser in dentistry: An innovative tool in modern dental practice. [2022]

5. Hungary pubmed.ncbi.nlm.nih.gov

[Laser in contemporary dentistry]. [2015]

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

Adverse events of fractionated carbon dioxide laser: review of 373 treatments. [2012]

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

A prospective study of fractional scanned nonsequential carbon dioxide laser resurfacing: a clinical and histopathologic evaluation. [2022]

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

Laser Resurfacing for Latin Skins: The Experience with 665 Cases. [2021]

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

Combined cervicofacial rhytidectomy and laser skin resurfacing. [2019]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Canine submandibular-gland hyaluronidase. Purification and properties. [2019]

12. United States 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. [2021]

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

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

14. England pubmed.ncbi.nlm.nih.gov

Crystallization and preliminary crystallographic analysis of recombinant hyaluronate lyase from Streptococcus suis. [2021]

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

Production of human hyaluronidase in a plant-derived protein expression system: plant-based transient production of active human hyaluronidase. [2023]