## Protocol Section
### Identification Module
**NCT ID:** NCT04382079

**Brief Title:** Honey Products for Cancer Patients With Oral Mucositis: a Randomized Controlled Trial

**Official Title:** Effects of Honey and Propolis on Head and Neck Cancer Patients With Oral Mucositis: a Randomized Controlled Trial

#### Organization Study ID Info
**ID:** N202001041
#### Organization
**Class:** OTHER
**Full Name:** Taipei Medical University
### Status Module
#### Completion Date
**Date:** 2022-04-15

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2020-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2020-05-22

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2021-04-15

**Type:** ESTIMATED

#### Start Date
**Date:** 2020-04-08

**Type:** ACTUAL

**Status Verified Date:** 2020-04

#### Study First Post Date
**Date:** 2020-05-11
**Type:** ACTUAL
**Study First Submit Date:** 2020-05-03
**Study First Submit QC Date:** 2020-05-06
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Taipei Medical University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The investigators plan to conduct a 3-year pioneering care research project for mucositis in cancer patients. These include: (1) an analysis of the incidence and severity of mucositis, severity, treatment methods, and treatment costs; (2) an RCT comparing the effectiveness of honey, Taiwan green propolis, and usual care in mucositis of cancer patients; (3) monitoring of related symptom changes using a smart bracelet device; (4) a measurement of IL-1, IL-6, IL-10, and TNF in saliva and (4) modeling of the trend of mucositis for alertness and search of essential parameters of the complications.

**Detailed Description:** Mucositis is common among cancer patients receiving radiotherapy and chemotherapy. A total of 80-100% of the patients are suffering from the mucositis pain; their regular dieting is disturbed, nutritional status deteriorated, and even treatment discontinued. Some self-paid medications like glutamine have been used to prevent mucositis before and during radiotherapy/chemotherapy. However, the cost of glutamine is relatively high (NT15,000 month/person) and its treatment efficacy and side effects are still to be determined. Randomized controlled trials (RCTs) and experiments have shown that honey and propolis may be used for the management of mucositis. Taiwan is a country of rich agriculture with unique bee products among which the longan honey demonstrates the most significant antibacterial effects; the green propolis has also been proved to comprise antibacterial, anti-inflammatory, and antioxidant effects. However, none of these propolis products have been specifically trialed for the management of mucositis of cancer patients.

Bee products have been concerned as potential sources of natural antioxidants such as flavonoids, phenolic acids, and terpenoids. Their potential treatment effects have caught the attention of the medical community. Accumulating evidence is supporting the use of bee products in mucositis caused by chemotherapy, radiotherapy, or both. However, systematic review and meta-analysis have suggested a low quality of the included RCTs, and this affects the applicability of the evidence in the real clinical scenario.

The investigators plan to conduct a 3-year pioneering care research project for mucositis in cancer patients. These include: (1) an analysis of the incidence and severity of mucositis, severity, treatment methods, and treatment costs; (2) an RCT comparing the effectiveness of honey, Taiwan green propolis, and usual care in mucositis of cancer patients; (3) monitoring of related symptom changes using a smart bracelet device; (4) a measurement of IL-1, IL-6, IL-10, and TNF in saliva and (4) modeling of the trend of mucositis for alertness and search of essential parameters of the complications. In the first year, our project will focus on the analysis of the incidence and severity of mucositis, treatment methods, and treatment costs. In the second year, the planned RCT will be carried out and changes in heart rate, stress, and fatigue of the patients are to be collected using the smart bracelet. In the third year, the investigators will conduct a deep machine learning of the clinical and serial test data to predict the changes in symptoms. The modeling is anticipated to provide important parameter combinations that assist the alerting of possible severe complications. The overall findings of this project shall the strategical references for applying bee products in the prevention and treatment of mucositis in cancer patients.

### Conditions Module

**Conditions:**

- Oral Mucositis

**Keywords:**

- head and neck cancer

- mucositis

- honey

- Taiwanese green propolis

- intelligent care

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 150

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Honey, 10 grams per pack, calories 33.4 calories, protein 0.05 grams, fat 0.07 grams, fructose + glucose 7.0 grams, sodium 0 mg.

Usage is three times a day after three meals. After oral care is required before use, use 10 grams of longan honey, circulate in the oral cavity for at least 30 seconds, and slowly swallow. Do not eat, drink, or gargle within 30 minutes of use.

**Intervention Names:**

- Dietary Supplement: honey

**Label:** honey

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Oil-soluble green propolis, propolis 100 mg / mL, dilute green propolis 200 times with edible oil, drink 0.5 mL each time, 3 times a day (a total of 50 mg).

Usage: three times a day, after three meals. After oral care is required before use, draw about 0.5ml of green propolis into the mouth, circulate in the oral cavity for at least 30 seconds, and slowly swallow. Do not eat, drink or gargle within 30 minutes of use.

**Intervention Names:**

- Dietary Supplement: propolis

**Label:** propolis

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Routine care to encourage oral care three times a day.

**Label:** control

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- honey

**Description:** Since the patient received radiation therapy, Taiwan Longan Honey has been used for a total of eight weeks.

Understand the changes of oral mucositis and various symptoms during this period

**Name:** honey

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- propolis

**Description:** Since the patient received radiation therapy, Taiwan green propolis has been used for a total of eight weeks.

Understand the changes of oral mucositis and various symptoms during this period

**Name:** propolis

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** measurement tool: National Cancer Institute Common Terminology Criteria for Adverse Events and The World Health Organization grading system

**Measure:** oral mucositis

**Time Frame:** twelve weeks

#### Secondary Outcomes

**Description:** measurement tool:Numerical Rating Scale,for pain status, range from 0 to 10, 10 was the most pain, 0 was no pain.

**Measure:** Numerical Rating Scale

**Time Frame:** twelve weeks

**Description:** measurement tool: Xerostomia Questionnaire

**Measure:** Xerostomia

**Time Frame:** twelve weeks

**Description:** measurement tool : Functional Assessment of Cancer Therapy Scale- Head and Neck, for patient's Quality of life (QoL), range from 0 to 100, score 100 means better outcome.

**Measure:** Functional Assessment of Cancer Therapy Scale- Head and Neck

**Time Frame:** twelve weeks

**Description:** measurement tool: Brief-Fatigue Inventory, range 0 to 10, 10 was the worst fatigue.

**Measure:** fatigue--Brief-Fatigue Inventory

**Time Frame:** Brief-Fatigue Inventory for two weeks.

**Description:** measurement tool: Visual Analogue Scale for fatigue, range 0 to 10, 10 was the worst fatigue.

**Measure:** fatigue--Visual Analogue Scale

**Time Frame:** Visual Analogue Scale for fatigue for twelve weeks.

**Description:** The patient collected this saliva before the start of radiotherapy, on the 7th, 14th, 21st day and at the end of radiation therapy, a total of 5 tubes of saliva at a time

**Measure:** IL-1, IL-6, IL-10,TNF

**Time Frame:** radiotherapy on Day 0, on the 7th, 14th, 21st day and on an average of 28 st day.

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* age≧20 years old
* diagnosed as head and neck cancer patients
* Plan to Receive radiation therapy
* Consciousness, ability to complete research assessment and willing to participate in research
* Patients can be communicated in Mandarin and Taiwanese, and complete the questionnaire on their own or with the help of researchers.

Exclusion Criteria:

* History of allergic to honey, propolis, various pollen, alcohol
* People with mental disorders or cognitive dysfunction
* Diabetes mellitus
* Critical of end of life patient

**Maximum Age:** 100 Years

**Minimum Age:** 20 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** tsaiwei@tmu.edu.tw

**Name:** Tsai-Wei Huang, PhD

**Phone:** +88627361661

**Phone Ext:** 6350

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Taipei county

**Contacts:**

***Contact 1:***

- **Email:** tsaiwei@tmu.edu.tw

- **Name:** Tsai-Wei Huang, PhD

- **Phone:** +88627361661

- **Phone Ext:** 6350

- **Role:** CONTACT

***Contact 2:***

- **Name:** Shao-Ching Jen, BS

- **Role:** SUB_INVESTIGATOR

**Country:** Taiwan

**Facility:** Taipei Medical University

**Status:** RECRUITING

**Zip:** 110

#### Overall Officials

**Official 1:**

**Affiliation:** Taipei Medical University

**Name:** Tsai-Wei Huang, PhD

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**Access Criteria:** Professor Huang will review the application to share IPD.

**Description:** oral mucositis severity, fatigue, pain, quality of life

**Info Types:**

- STUDY_PROTOCOL

- CSR

**IPD Sharing:** YES

**Time Frame:** Before radiotherapy, until 12 weeks later

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005759

- Term: Gastroenteritis

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000009059

- Term: Mouth Diseases

- ID: D000009057

- Term: Stomatognathic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC07

- Name: Mouth and Tooth Diseases

- Abbrev: BC06

- Name: Digestive System Diseases

### Condition Browse Module - Browse Leaves

- ID: M9348

- Name: Head and Neck Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16070

- Name: Stomatitis

- Relevance: HIGH

- As Found: Oral Mucositis

- ID: M26955

- Name: Mucositis

- Relevance: HIGH

- As Found: Mucositis

- ID: M8875

- Name: Gastroenteritis

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12019

- Name: Mouth Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12017

- Name: Stomatognathic Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000052016

- Term: Mucositis

- ID: D000013280

- Term: Stomatitis

### Intervention Browse Module - Ancestors

- ID: D000000890

- Term: Anti-Infective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M14295

- Name: Propolis

- Relevance: HIGH

- As Found: Depleted

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: T364

- Name: Bee Products

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000011429

- Term: Propolis

### Misc Info Module

- Version Holder: 2024-05-24
