MOM's PAIN (Methylene Blue for Oral Mucositis' PAIN)

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well methylene blue works in treating patients with cancer and pain associated with oral mucositis. Methylene blue may relieve pain associated with oral mucositis.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To evaluate the efficacy of methylene blue (MB) in reducing the severity of mucositis-related pain, measured by numeric rating scale (NRS), in cancer patients who underwent or are undergoing chemotherapy or radiation therapy. OUTLINE: Patients are randomized to 1 of 4 groups. GROUP 1: Patients receive lower dose methylene blue orally (PO) to swish and spit for 5 minutes every 6 hours then receive standard of care therapy. GROUP 2: Patients receive medium dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy. GROUP 3: Patients receive higher dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy. GROUP 4: Patients receive standard of care therapy. After completion of study treatment, patients are followed up at 1, 2, 7, and 30 days.

Official Title
-----------------
Randomized Controlled Trial Comparing 4 Intervention Arms, Including 3 Different Concentrations of Methylene Blue Oral Rinse Combined With Conventional Therapy and Conventional Therapy, in Patients With Intractable Pain Associated With Oral Mucositis

Conditions
-----------------
Malignant Neoplasm, Oral Pain, Stomatitis

Intervention / Treatment
-----------------
* Other: Best Practice
* Drug: Methylene Blue
* Drug: Methylene Blue
* Drug: Methylene Blue


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with a cancer diagnosis, receiving chemotherapy, radiation therapy or the combination Patients with a current diagnosis of oral mucositis Patients with pain and oral dysfunction associated with oral mucositis despite conventional therapy Voluntary written consent Patient must agree to use of contraception or abstinence from sex during the treatment period and for 30 days after patient's last dose Exclusion Criteria: Patients with known allergy to MB Patients taking medications with known significant drug interactions Pregnant or lactating patients Patients who are cognitively impaired and unable to consent for the study Patients with risk of broncho-aspiration based on documented swallowing test by a speech pathologist (if available) Patients with known history of G6PD deficiency Patients undergoing any other experimental intervention for oral mucositis Patients who have no pain or impairment in oral function, patients who are not symptomatic Patients with head and neck cancer Patients on serotonergic drugs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (lower dose methylene blue, standard of care)<br>Patients receive lower dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy. | Other: Best Practice<br>* Given standard of care therapy<br>* Other names: standard therapy;Drug: Methylene Blue<br>* Given lower dose PO<br>* Other names: Vitableu;|
| Experimental: Group 2 (medium dose methylene blue, standard of care)<br>Patients receive medium dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy. | Other: Best Practice<br>* Given standard of care therapy<br>* Other names: standard therapy;Drug: Methylene Blue<br>* Given medium dose PO<br>* Other names: Vitableu;|
| Experimental: Group 3 (higher dose methylene blue, standard of care)<br>Patients receive higher dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy. | Other: Best Practice<br>* Given standard of care therapy<br>* Other names: standard therapy;Drug: Methylene Blue<br>* Given higher dose PO<br>* Other names: Vitableu;|
| Active Comparator: Group 4 (standard of care)<br>Patients receive standard of care therapy. | Other: Best Practice<br>* Given standard of care therapy<br>* Other names: standard therapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain Scores Assessed Within the Numeric Rating Scale (NRS) Component of the Modified Harris Mucositis-related Pain Assessment Tool | Oral mucositis pain reduction (measured by using the Numeric Rating Scale (NRS); from 0, representing no pain, to 10, representing the worst possible pain) from baseline to 7 days post treatment. The pain scale is included in the Modified Harris mucositis-related pain assessment tool. | Baseline up to day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Oral Function Burden (OFB) Scores | Oral functioning (eat, swallow, talk: unable=2, difficulty=1, able=0. Oral functioning score is the total score of 3 categories, ranged 0-6). Scale is included in the Modified Harris mucositis-related pain assessment tool. Measurements are obtained at day 0, 1, 2, and 7. Modified Harris mucositis-related pain assessment tool. Lowest value=0 representing normal. Highest value =6 representing worst outcome. | Baseline up to day 7 | 
| World Health Organization Oral Mucositis Severity Grades | Used the WHO grading system (0= no mucositis, 3=severe mucositis) The clinical severity of the OM was documented only at enrollment point to the study. Most of the patients had the grade 3 mucositis (Soreness/erythema + ulceration + ability to use a liquid diet only), per World Health Organization criteria. See table below which indicates the description of the various grades. Grade Description 0 No changes Soreness/erythema Soreness/erythema + ulceration + ability to eat solid foods Soreness/erythema + ulceration + ability to use a liquid diet only Secondary endpoint included oral functioning burden (0=normal, 6= worse oral function) (OFB; measured on a scale of 0, representing normal, to 6, meaning total inability, reflecting a total score of three categories: the ability to eat, swallow, and talk, each scored as unable = 2, difficult = 1, able = 0). | Up to day 2 | 
| Morphine Equivalent Daily Doses (MEDD) | Morphine equivalent daily dose (MEDD) used for oral mucositis pain at 2 post MB administration. Before the study was implemented, it was observed that many patients had pain resolved just within a few doses. Therefore, the study aimed to cover only 100 cc of MB, which typically last about 2 days. Some patients requested more MB after the two days which had to be provided by the pharmacy and ordered by the primary team and paid by patient insurance. This was considered out of the study, but the patients were still followed. Also, there was no average, only self-reported level of pain from the patient at point of data collection. | Baseline to Day 2 | 
| Pain Duration | Measured the days the patient was in pain. The study aimed to cover only 100 cc of MB, which typically last about 2 days. Some patients requested more MB after the two days which had to be provided by the pharmacy and ordered by the primary team and paid by patient insurance. This was considered out of the study, but the patients were still followed. We followed for 30-90 days (no treatment for 30-90 days), only to observe for AEs. Also, there was no average, only self-reported level of pain from the patient at point of data collection. | Up to 30-90 days |