Evaluating Chinese Medicine Oral Rinse for Irradiated Oral Mucositis in Head & Neck Cancer Patients

December 16, 2022 updated by: Au Kwok Yin, Chinese University of Hong Kong

Evaluating Efficacy and Safety of Chinese Medicine Oral Rinse in Treating and Preventing Irradiated Oral Mucositis in Head-and-Neck Cancer Patients - a Pilot Trial

Approximately 60% and 90% of patients with head and neck (H&N) cancers receiving standard radiotherapy (RT) and chemoradiotherapy (chemo-RT) will develop oral mucositis respectively. Oral mucositis (OM) is one of the dose-limiting adverse events which can also lead to emotional and nutritional problems. Clinically, it is usually observed by the end of first week of RT (after 10 Gy) and reaches peak damage in 14-21 days or by the end of treatment. Healing then takes approximately 2 to 3 weeks after completion of RT. For the Chinese Medicine (CM) interventions, many studies have been reviewed on the efficacy of mouthwash or internal herbal decoction to OM. Although some positive results were observed, most of them were performed by applying different assessment tools and lack of quality of life (QOL) or self-reported symptoms assessment. In addition, the intervention time and follow-up period were usually insufficient (stopped at the end of RT), therefore they could not review the long-term efficacy of CM according to normal progression of OM and the safety of using CM. Therefore, we hope this pilot study can evaluate the efficacy and safety of CM in a strict protocol.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Approximately 60% and 90% of patients with head and neck (H&N) cancers receiving standard radiotherapy (RT) and chemoradiotherapy (chemo-RT) will develop oral mucositis respectively. Oral mucositis (OM) is one of the dose-limiting adverse events which can also lead to emotional and nutritional problems. Clinically, it is usually observed by the end of first week of RT (after 10 Gy) and reaches peak damage in 14-21 days or by the end of treatment. Healing then takes approximately 2 to 3 weeks after completion of RT.

The risk of OM is especially high in NPC patients who receive concomitant chemotherapy, receive a total dose over 5,000 Gy, treat with altered fractionation radiation schedules, have bad oral hygiene status, do not use antibiotic at early stage mucositis, have smoking history, drink alcohol, have problems in nutritional status like anorexia, malnutrition, lack of vitamins, restriction of food due to specific dietary requirements, have haematological disease or non-ideal hematological status, have advanced localization of tumors and stage, receive immunotherapy, have pre-existing dry mouth (Xerostomia), have episodes of OM during prior treatment cycles and low BMI, etc.

According to some weighed guidelines such as The Multinational Association of Supportive Care in Cancer and International Society for Oral Oncology (MASCC/ISOO) guidelines for the management of OM, recent systematic reviews and researches, there are mainly several sections for intervention: (1) Basic oral care, (2) Anti-inflammatory agents, (3) Photobiomodulation, (4) Cryotherapy, (5) Antimicrobials, coating agents, anesthetics, and analgesics, (6) Growth factors and cytokines, and (7) Natural and miscellaneous. We can summarize several suggestions for the prevention of OM in H&N cancer adults receiving RT from the above protocols: multiagent combination oral care protocols (increasing the awareness of good oral hygiene), professional dental care (a desirable option before or during cancer therapy for local and systemic infections from odontogenic sources), benzydamine mouthwash (as the anti-inflammaotary agents for moderate dose of RT (<50 Gy)) and intraoral photobiomodulation therapy using low-level laser therapy. Over the years, the number of interventions studied for OM and their quality of study design have been dramatically increasing. However, since there are still some advantages and disadvantages for some suggested agents, some clinical settings have not yet been recommended with appropriate intervention. Natural and miscellaneous agents are also reviewed in the past years while honey is suggested for prevention of OM in patients with H&N cancer who receive treatment with either RT or chemo-RT. However, if honey is applied repeatedly on a daily basis for a longer period, we have to be cautions with its deleterious effects. A strict oral hygiene protocol has to be followed to prevent dental caries.

For the Chinese Medicine (CM) interventions, many studies have been reviewed on the efficacy of mouthwash or internal herbal decoction to OM. Although some positive results were observed, most of them were performed by applying different assessment tools and lack of quality of life (QOL) or self-reported symptoms assessment. In addition, the intervention time and follow-up period were usually insufficient (stopped at the end of RT), therefore they could not review the long-term efficacy of CM according to normal progression of OM and the safety of using CM. Therefore, we hope this pilot study can evaluate the efficacy and safety of CM in a strict protocol.

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Hong Kong Institute of Integrative Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: Patients who

  • are aged ≥18, with known diagnosis of non-metastatic hypopharyngeal cancer, laryngeal cancer, lip and oral cavity cancer, nasopharyngeal cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, and salivary gland cancer.
  • are the first time to receive RT to the primary tumor in the area of the head or face, neck, or oral cavity.
  • start RT recently within 14 days.
  • are assessed by CMPs for the condition of oral mucositis according to modified World Health Organization (WHO) Mucositis Grades with Grade ≦1.
  • have Karnofsky Performance Status (KPS) ≥ 60 (patients require occasional assistance, but is able to care for most personal needs will be 60 or above).
  • are able to read or understand and sign the consent form.

Exclusion Criteria: Patients who

  • receive concurrent chemo-radiation.
  • have known medication on bacterial or fungal infections of oropharynx at recruitment.
  • have other known diseases such as serious and uncontrolled Diabetes mellitus (with symptom of delayed wound healing over the past half year) or hyperthyroidism (with symptom of serious oral dryness over the past half year), known connective vascular disorders or known Human Immunodeficiency Virus (HIV) infections etc.
  • have known history of allergy to CMORF-I ingredients or Glucose-6-Phosphate Dehydrogenase (G6PD) patients.
  • are known pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intervention Group: Chinese Medicine Oral Rinse and Standard Care
  • Prescription and oral rinsing with Chinese Medicine Oral Rinse Formula-I (CMORF-I) which mainly consists of the Nong's concentrated CM granules of Wu Wei Xiao Du Yin and other ingredients.
  • Standard care will be following the indications provided by patient's western medical doctor.
  • Patients should not take any other TCM and non-prescribed medication and nutritional supplements during the intervention period.
Drug: Chinese Medicine Oral Rinse Formula-I (CMORF-I)
  • Prescription of Chinese Medicine Oral Rinse Formula-I (CMORF-I)

  • Instruction to rinse:

    1. The above amount of concentrated CM granules will be divided and packed in 4 bags per day.
    2. Dissolve 1 bag of concentrated CM granules with 150ml 80'C boiled hot water, and wait for 20 mins to cool down.
    3. Clean the mouth thoughtfully by rinsing with 150ml of distilled water for 2 minutes.
    4. Rinse the mouth thoughtfully with one-third of the dissolved and cooled CM oral rinse, gargle, expel after 3 minutes, do not swallow and repeat twice.
    5. To ensure better contact of the CM oral rinse in all parts and folds of the oral cavity, our research assistant and CMP will guide the patients to fully agitate the mouth, use the tongue to stir repeatedly among the teeth, cheeks and palate surface, and to raise the tip of the tongue for a moment and tilt the head back.
    6. 4 times a day (half an hour after every meal, half an hour before sleep), from baseline to 2 weeks after RT.
Other Names:
  • CMORF-I
Other: Standard Care
• Standard care including normal saline or medical mouthwash, optional analgesics and antibiotics will be offered by hospital.
Placebo Comparator: Control Group: Placebo and Standard Care
  • Placebo: The placebo consists of an inert substance, made of starch filler, flavor and colorings. It is also manufactured under GMP standard. To ensure blinding, the CMORF-I formula and placebo will be indistinguishable in appearance, smell and favour.
  • Standard care will be following the indications provided by patient's western medical doctor.
  • Patients should not take any other TCM and non-prescribed medication and nutritional supplements during the intervention period.
Other: Standard Care
• Standard care including normal saline or medical mouthwash, optional analgesics and antibiotics will be offered by hospital.
Other: Placebo
Placebo granules, instruction is the same as CMORF-I.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of the proportion of the most severe modified WHO Mucositis Grades
Time Frame: From baseline to week 12 after the end of RT during post intervention period
  • Comparison of the proportion of the most severe modified WHO Mucositis Grades among intervention and control groups during RT.
  • Grades of the OM will be assessed by a Registered Chinese medicine practitioner (CMP) at baseline and day 7 (±1d) of every week during the RT, the most severe grades during the treatment will be regarded for data analysis.
  • Modified WHO Mucositis Grading Scale: Grade 0 (none) - normal; Grade 1 (mild) - soreness/erythema; Grade 2 (moderate) - erythema, ulcer/pseudo-membranes, can eat solids (erythema with ulcers less than 1 cm); Grade 3 (severe) - ulcer/pseudo-membrane, (erythema with ulcers more than 1cm) requires liquid diet only; Grade 4 (life-threatening) - ulcer with hemorrhage and necrosis, alimentation not possible; cancer treatment that results in or contribute to death is reported separately.
From baseline to week 12 after the end of RT during post intervention period

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
10cm visual analogue scale (VAS) of oral pain
Time Frame: Day 3 and day 7 (±1d) of every week during intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
It is a measurement of oral pain. Scores are recorded by making a handwritten mark on a 10-cm line that represents a continuum between "no pain" on the left and "worst pain" on the right.
Day 3 and day 7 (±1d) of every week during intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
Oral Mucositis Daily Questionnaire (OMDQ) (validated Chinese version with modification)
Time Frame: Day 3 and day 7 (±1d) of every week during intervention period, once a week during post intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
It is a measurement of self-reported quality of life. It contains 10 items, for most questions in the OMDQ, a higher score indicated a worsening in symptom severity or more interference with functional activity. For the question pertaining to overall health, a higher score indicates better overall health status.
Day 3 and day 7 (±1d) of every week during intervention period, once a week during post intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (Head and Neck) (EORTC QLQ-C30) (Hong Kong Cantonese version)
Time Frame: Day 7 (±1d) of every week during intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
It is a specific measurement of self-reported quality of life for Head and Neck cancer patients. It consists of 30 questions that indicate the extent to which you have experienced these symptoms or problems during the past week. Scoring from 1 "Not at all" to 4 "Very much".
Day 7 (±1d) of every week during intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (Head and Neck) (EORTC QLQ-H&N35) (Hong Kong Cantonese version)
Time Frame: Day 7 (±1d) of every week during intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
It is a specific measurement of self-reported quality of life for Head and Neck cancer patients. It consists of 35 questions that indicate the extent to which you have experienced these symptoms or problems during the past week. Scoring from 1 "Not at all" to 4 "Very much".
Day 7 (±1d) of every week during intervention period, end of week 4, week 8 and week 12 after the end of RT during post intervention period.
Body mass index (BMI)
Time Frame: From baseline to week 12 after the end of RT during post intervention period
It is a measurement of the amount of body fat based on height and weight that applies to adult men and women. It can assess and monitor the risk of OM to a certain extent.
From baseline to week 12 after the end of RT during post intervention period
Number of analgesic and antibiotics use daily
Time Frame: From baseline to week 12 after the end of RT during post intervention period
It can assess and monitor the conditions of OM.
From baseline to week 12 after the end of RT during post intervention period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Investigators

  • Principal Investigator: KWOK YIN AU, Doctor of Medicine, Hong Kong Institute of Integrative Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 31, 2023

Primary Completion (Anticipated)

May 31, 2024

Study Completion (Anticipated)

November 30, 2024

Study Registration Dates

First Submitted

November 6, 2022

First Submitted That Met QC Criteria

December 16, 2022

First Posted (Actual)

December 27, 2022

Study Record Updates

Last Update Posted (Actual)

December 27, 2022

Last Update Submitted That Met QC Criteria

December 16, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CM Rinse_OMRT

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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