Trial Outcomes & Findings for MOM's PAIN (Methylene Blue for Oral Mucositis' PAIN) (NCT NCT03469284)

Last Updated: 2023-04-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

69 participants

Primary outcome timeframe

Baseline up to day 7

Results posted on

2023-04-25

Participant Flow

Recruitment Period: March 1, 2019, and December 01, 2020- Conducted at The University of Texas MD Anderson Cancer Center.

69 participants signed consent, 9 participants withdrew (3 dropped out of the trial because they were randomized out of the methylene blue group, 5 had progression of disease and could not continue the trial, and 1 was enrolled but withdrew before starting the medication.)

Participant milestones

Participant milestones
Measure	Conventional Therapy (Controlled Arm) Participants receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.025% Participants receive 0.025% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.05% Participants receive 0.05% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.1% Participants receive 0.1% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
Overall Study STARTED	16	15	14	15
Overall Study COMPLETED	16	15	14	15
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Conventional Therapy (Controlled Arm) n=16 Participants Participants receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.025% n=15 Participants Participants receive 0.025% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.05% n=14 Participants Participants receive 0.05% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.1% n=15 Participants Participants receive 0.1% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Total n=60 Participants Total of all reporting groups
Age, Continuous	48 years n=5 Participants	45 years n=7 Participants	43 years n=5 Participants	32 years n=4 Participants	43 years n=21 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	22 Participants n=21 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	38 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	48 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants
Region of Enrollment United States	16 participants n=5 Participants	15 participants n=7 Participants	14 participants n=5 Participants	15 participants n=4 Participants	60 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline up to day 7

Outcome measures

Outcome measures
Measure	Conventional Therapy (Controlled Arm) n=16 Participants Participants receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.025% n=15 Participants Participants receive 0.025% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.05% n=14 Participants Participants receive 0.05% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.1% n=15 Participants Participants receive 0.1% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
Change in Pain Scores Assessed Within the Numeric Rating Scale (NRS) Component of the Modified Harris Mucositis-related Pain Assessment Tool	1.69 score on a scale Standard Deviation 3.09	5.2 score on a scale Standard Deviation 2.81	4.54 score on a scale Standard Deviation 2.93	5.15 score on a scale Standard Deviation 2.64

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Conventional Therapy (Controlled Arm) n=16 Participants Participants receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.025% n=15 Participants Participants receive 0.025% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.05% n=14 Participants Participants receive 0.05% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.1% n=15 Participants Participants receive 0.1% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
Change in Oral Function Burden (OFB) Scores	0.81 score on a scale Standard Deviation 1.11	2.47 score on a scale Standard Deviation 1.55	2.79 score on a scale Standard Deviation 1.72	2.87 score on a scale Standard Deviation 1.60

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Conventional Therapy (Controlled Arm) n=16 Participants Participants receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.025% n=15 Participants Participants receive 0.025% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.05% n=14 Participants Participants receive 0.05% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.1% n=15 Participants Participants receive 0.1% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
World Health Organization Oral Mucositis Severity Grades Grade 2	1 Participants	0 Participants	1 Participants	4 Participants
World Health Organization Oral Mucositis Severity Grades Grade 3	15 Participants	15 Participants	13 Participants	11 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Conventional Therapy (Controlled Arm) n=16 Participants Participants receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.025% n=15 Participants Participants receive 0.025% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.05% n=14 Participants Participants receive 0.05% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.1% n=15 Participants Participants receive 0.1% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
Morphine Equivalent Daily Doses (MEDD)	117.5 mg Interval 16.4 to 825.0	115 mg Interval 12.5 to 535.0	107 mg Interval 15.0 to 648.0	120 mg Interval 5.0 to 3153.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Conventional Therapy (Controlled Arm) n=16 Participants Participants receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.025% n=15 Participants Participants receive 0.025% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.05% n=14 Participants Participants receive 0.05% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.	Conventional Therapy + Methylene Blue (MB) 0.1% n=15 Participants Participants receive 0.1% dose methylene blue PO to swish and spit for 5 minutes every 6 hours then receive standard of care therapy.
Pain Duration	5.5 days Interval 3.0 to 8.0	8 days Interval 2.0 to 90.0	6 days Interval 1.0 to 43.0	5 days Interval 2.0 to 30.0

Adverse Events

Conventional Therapy (Controlled Arm)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Conventional Therapy + Methylene Blue (MB) 0.025%

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Conventional Therapy + Methylene Blue (MB) 0.05%

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Conventional Therapy + Methylene Blue (MB) 0.1%

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Carlos Roldan, Associate Professor, Pain Medicine

UT MD Anderson Cancer Center

Phone: (713) 563-7402

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place