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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a methylene blue mouthwash can relieve oral pain from mucositis in cancer patients more effectively than the usual mouthwash. Oral mucositis, a painful condition, often results from cancer treatments. The trial includes two groups: one using the standard mouthwash and the other using methylene blue (also known as Methylene Blue Oral Rinse). It seeks participants who have cancer, are hospitalized, and suffer from mouth pain due to mucositis. Participants must be able to give consent and should not have conditions that would adversely react to methylene blue. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that methylene blue mouthwash is generally safe for individuals experiencing mouth pain from oral mucositis. Studies have found it effective for pain unrelieved by strong painkillers like opioids. Most patients tolerate it well, with few side effects. In one study, only 4.6% of patients experienced side effects. Some reported a brief burning sensation, and a few noticed temporary blue discoloration of their teeth. Overall, methylene blue mouthwash appears to be a safe option for managing pain related to oral mucositis in cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Methylene Blue mouthwash is unique because it uses methylene blue, a compound that may offer pain relief for oral mucositis by reducing inflammation and promoting healing in the mouth. Unlike standard mouthwashes, which typically focus on soothing with ingredients like salt or baking soda, methylene blue has a distinct mechanism of action that targets the underlying issues more directly. Researchers are excited about the potential for this mouthwash to offer faster and more effective relief for patients experiencing painful oral mucositis.

What evidence suggests that methylene blue mouthwash might be an effective treatment for oral mucositis pain?

Research has shown that methylene blue mouthwash, which participants in this trial may receive, can help reduce pain from oral mucositis, a common and painful condition in cancer patients. Studies have found that this mouthwash can significantly lessen pain for several hours. In some cases, it has also reduced the need for pain medications like opioids. Patients reported feeling more comfortable in their mouths after using methylene blue rinses compared to standard treatments. This trial will compare the effects of methylene blue mouthwash with a standard care mouthwash, suggesting that methylene blue could be a promising option for managing oral pain in cancer patients. ^{1 2 4 6 7}

Who Is on the Research Team?

Regina M. Mackey, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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

Able to provide informed consent

I am currently diagnosed with cancer.

I am currently admitted to a hospital.

Exclusion Criteria

I am under 18 years old.

Pregnant or nursing women

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9632023/

Methylene blue for intractable pain from oral mucositis ... We aimed to assess the safety and effectiveness of methylene blue (MB) oral rinse for OM pain in patients receiving cancer therapy.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10417523/

Methylene Blue for the Treatment of Radiation-Induced ... Methylene blue oral rinse (MBOR) significantly decreased oral mucositis pain for at least 6.2 h (median + SD 8 ± 1.68 before vs. 2 ± 2.20 after ...

3. scientificarchives.com scientificarchives.com/article/methylene-blue-oral-rinse-an-effective-alternative-for-the-treatment-of-pain-in-oral-mucositis-during-head-and-neck-cancer-treatment

Methylene Blue Oral Rinse: An Effective Alternative for the ... As an oral rinse, it has demonstrated efficacy in ameliorating pain intensity and reducing opioid requisites vis-à-vis conventional therapy alone for ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20541617

Methylene Blue Mouthwash for Oral Mucositis Pain in Cancer Oral intake will improve after six doses of methylene blue mouthwash compared to usual care.

5. jnccn.org jnccn.org/downloadpdf/journals/jnccn/19/5/article-p521.pdf

Methylene Blue for the Treatment of Intractable Pain From ... Conclusions: MB oral rinse is an effective and safe treatment for refractory pain from oral mucositis related to cancer treatment. Background. J ...

6. bmcmedicine.biomedcentral.com bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02579-8

Methylene blue for intractable pain from oral mucositis related ... MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects.

7. jnccn.org jnccn.org/abstract/journals/jnccn/19/5/article-p521.xml

Methylene Blue for the Treatment of Intractable Pain From ... Few patients experienced adverse effects of MB oral rinse (n=13; 4.6%); 10 had a transient burning sensation, 2 had transient blue discoloration of the teeth ...