Methylene Blue Mouthwash for Oral Mucositis Pain

Overseen By Regina M. Mackey, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Mayo Clinic

Disqualifiers: Pediatric age, Pregnant, G6PD deficiency, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 3 days

49 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether a special mouthwash called methylene blue can better relieve mouth pain in cancer patients with oral mucositis compared to the usual mouthwash. Oral mucositis is a common and painful side effect of cancer treatments. Anecdotal experience has suggested that methylene blue (MB) oral rinse may be an effective and safe treatment of oral pain due to mucositis in patients with cancer.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Methylene Blue Mouthwash for reducing oral mucositis pain?

Research shows that Methylene Blue Mouthwash can significantly reduce pain from oral mucositis in cancer patients, with studies reporting decreased pain levels and improved oral function. It has been effective in providing prolonged pain relief and reducing the need for strong painkillers in patients with severe oral mucositis pain. ^{1 2 3 4 5}

Is methylene blue mouthwash safe for humans?

Methylene blue mouthwash has been studied for treating oral pain in cancer patients and is generally considered safe, with minimal side effects reported in studies. ^{1 2 3 4 6}

How is the drug methylene blue oral rinse unique for treating oral mucositis pain?

Methylene blue oral rinse is unique because it offers a noninvasive, safe, and cost-effective way to manage severe oral mucositis pain, especially when traditional treatments like systemic painkillers fail. It works by chemically targeting the affected areas to provide prolonged pain relief, allowing patients to eat and improving their quality of life. ^{1 2 3 4 5}

Research Team

Regina M. Mackey, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for cancer patients with severe mouth sores (Grade 3-4 oral mucositis) causing pain, who are currently hospitalized. Participants must have an active cancer diagnosis and be able to give informed consent.

Inclusion Criteria

I am currently diagnosed with cancer.

I am currently admitted to a hospital.

I have pain due to mouth sores.

Exclusion Criteria

Pregnant or nursing women

I am under 18 years old.

I am not allergic to methylene blue and do not have G6PD deficiency.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either methylene blue mouthwash or standard of care mouthwash for oral mucositis pain

3 days

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Aqueous Mouth Rinse
• Methylene Blue Oral Rinse

Trial Overview The study is testing if methylene blue mouthwash can better manage pain from severe mouth sores in cancer patients compared to the standard care mouthwash typically used for this condition.

Participant Groups

Group I: Methylene Blue Mouthwash Group Experimental Treatment 1 Intervention

Patients receive Methylene Blue mouthwash as needed on study.

Group II: Standard of Care Mouthwash Group Active Control 1 Intervention

Patients receive standard of care mouthwash as needed on study.

Methylene Blue Oral Rinse is already approved in United States for the following indications:

Approved in United States as Methylene Blue Oral Rinse for:

• Oral mucositis pain in patients with cancer

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

A retrospective study of 281 cancer patients showed that methylene blue (MB) oral rinse significantly reduced pain from oral mucositis, with pain scores dropping from an average of 7.7 to 2.51 after treatment (P<.0001).

The treatment was found to be safe, with only 4.6% of patients experiencing mild adverse effects, such as a transient burning sensation or blue discoloration, indicating that MB oral rinse is a viable option for managing severe oral pain in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylene Blue for the Treatment of Intractable Pain From Oral Mucositis Related to Cancer Treatment: An Uncontrolled Cohort. Roldan, CJ., Chung, M., Feng, L., et al.[2021]

In a phase 2 clinical trial involving 60 patients undergoing cancer therapy, methylene blue (MB) oral rinse significantly reduced pain scores and improved oral function compared to conventional therapy alone.

The treatment was generally safe, with minimal adverse effects; however, some patients experienced a burning sensation, leading to one discontinuation, indicating that while effective, monitoring for discomfort is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylene blue for intractable pain from oral mucositis related to cancer treatment: a randomized phase 2 clinical trial. Roldan, CJ., Huh, B., Song, J., et al.[2022]

Methylene blue oral rinse significantly reduced oral mucositis pain in head and neck cancer patients undergoing radiation therapy, with pain levels dropping from an average of 8 to 2 on a scale of 0-10, lasting for at least 6.2 hours.

The treatment also improved oral function, allowing 36% of patients who previously needed feeding tubes to resume normal eating, with minimal adverse events reported in only 15% of cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylene Blue for the Treatment of Radiation-Induced Oral Mucositis during Head and Neck Cancer Treatment: An Uncontrolled Cohort. Roldan, CJ., Rosenthal, DI., Koyyalagunta, D., et al.[2023]

A case series of 5 patients with severe oral mucositis pain showed that a 0.05% methylene blue mouth rinse provided effective and sustained pain relief for up to 3 weeks, improving their quality of life and enabling oral feeding.

The use of methylene blue significantly reduced the need for opioids, indicating it is a safe, cost-effective alternative for managing intractable pain in cancer patients suffering from oral mucositis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylene Blue for the Treatment of Intractable Pain Associated with Oral Mucositis. Roldan, CJ., Nouri, K., Chai, T., et al.[2018]

In a case series involving 11 patients who underwent bilateral preprosthetic surgery, the use of blue®m mouthwash on one side significantly reduced pain and inflammation compared to the untreated side after seven days of application.

The study found that the mouthwash was well-accepted by patients and led to improved healing, as indicated by a lower number of inflammation pixels on the test side, suggesting its potential benefits for post-surgical recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mouthwash with Active Oxygen (blue®m) Reduces Postoperative Inflammation and Pain. Mattei, BM., Imanishi, SAW., de Oliveira Ramos, G., et al.[2021]

Rebamipide mouthwash significantly reduces the incidence of severe oral mucositis in patients undergoing chemoradiotherapy for head and neck cancers, with an odds ratio of 0.29 indicating a strong protective effect against grade 3-4 mucositis.

While rebamipide is effective in preventing severe mucositis, it is associated with a higher rate of adverse events (19.4% to 26.0%) compared to placebo (6.1% to 11.6%), suggesting the need for further evaluation of its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of rebamipide mouthwash therapy for radiotherapy and chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis. Akagi, S., Fujiwara, T., Nishida, M., et al.[2022]

References

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

Methylene Blue for the Treatment of Intractable Pain From Oral Mucositis Related to Cancer Treatment: An Uncontrolled Cohort. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Methylene blue for intractable pain from oral mucositis related to cancer treatment: a randomized phase 2 clinical trial. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Methylene Blue for the Treatment of Radiation-Induced Oral Mucositis during Head and Neck Cancer Treatment: An Uncontrolled Cohort. [2023]

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

Methylene Blue for the Treatment of Intractable Pain Associated with Oral Mucositis. [2018]

5. Egypt pubmed.ncbi.nlm.nih.gov

Mouthwash with Active Oxygen (blue®m) Reduces Postoperative Inflammation and Pain. [2021]

6. England pubmed.ncbi.nlm.nih.gov

The effectiveness of rebamipide mouthwash therapy for radiotherapy and chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis. [2022]