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

Phase 2

Completed

Conditions: Oral Pain
Stomatitis
Malignant Neoplasm

Interventions: Other: Best Practice
Drug: Methylene Blue

Registration Number: NCT03469284

Lead Sponsor: M.D. Anderson Cancer Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 69

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 (lower dose methylene blue, standard of care)	Best Practice	Patients receive lower dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
Group 2 (medium dose methylene blue, standard of care)	Best Practice	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 (higher dose methylene blue, standard of care)	Best Practice	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 (standard of care)	Best Practice	Patients receive standard of care therapy.
Group 1 (lower dose methylene blue, standard of care)	Methylene Blue	Patients receive lower dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
Group 2 (medium dose methylene blue, standard of care)	Methylene Blue	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 (higher dose methylene blue, standard of care)	Methylene Blue	Patients receive higher dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.

Primary Outcome Measures

Name	Time	Method
Change in Pain Scores Assessed Within the Numeric Rating Scale (NRS) Component of the Modified Harris Mucositis-related Pain Assessment Tool	Baseline up to day 7	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.

Secondary Outcome Measures

Name	Time	Method
Change in Oral Function Burden (OFB) Scores	Baseline up to day 7	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.
World Health Organization Oral Mucositis Severity Grades	Up to day 2	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 1. Soreness/erythema 2. Soreness/erythema + ulceration + ability to eat solid foods 3. 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).
Morphine Equivalent Daily Doses (MEDD)	Baseline to Day 2	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.
Pain Duration	Up to 30-90 days	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.