Protein Supplementation for Radiation- Induced Oral Mucositis in Head and Neck Cancer Patients Receiving Radiotherapy

N/ANot Yet RecruitingNCT07531563

Cancer Institute and Hospital, Chinese Academy of Medical Sciences504 enrolled

Overview

This clinical trial aims to evaluate whether oral supplementation with a hydrolyzed whey protein formula ("TeYiShu") can reduce the incidence of severe radiation-induced oral mucositis and improve prealbumin levels in patients undergoing radiotherapy for head and neck squamous cell carcinoma (HNSCC). The study will compare the protein supplement to an isocaloric placebo without protein, maintaining equal caloric intake across groups. Participants will receive either the protein supplement or placebo daily throughout the course of radiotherapy. The primary outcomes are the incidence of grade ≥3 oral mucositis, assessed using the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria, and changes in serum prealbumin levels. Secondary outcomes include the time to onset and resolution of mucositis, nutritional status changes, adverse events, and quality of life measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Cancer Module (EORTC QLQ-H\&N35).

This study is a randomized, controlled clinical trial designed to evaluate the effect of oral hydrolyzed whey protein supplementation on radiation-induced oral mucositis and nutritional status in patients with head and neck squamous cell carcinoma (HNSCC) receiving radiotherapy. Participants will be assigned to receive either a hydrolyzed whey protein formula ("TeYiShu") or an isocaloric placebo without protein during the course of radiotherapy, in addition to standard nutritional counseling and baseline nutrition support. The primary objectives are to determine whether protein supplementation reduces the incidence of Grade 3 or higher radiation-induced oral mucositis, assessed according to the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria, and improves serum prealbumin levels from baseline to the end of radiotherapy. Secondary objectives include evaluation of time to onset and resolution of oral mucositis, changes in body weight and other indicators of nutritional status, adverse events, and changes in quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Cancer Module (EORTC QLQ-H\&N35). The study aims to clarify whether high-protein oral nutritional supplementation can improve treatment tolerance and supportive care outcomes in patients undergoing radiotherapy for head and neck cancer.

Interventions

Hydrolyzed Whey Protein Oral SupplementDIETARY_SUPPLEMENT

A liquid oral supplement containing hydrolyzed whey protein, administered daily during the entire course of radiotherapy. Each 200mL bottle provides approximately 24g of protein. The supplement is given in addition to standard nutritional counseling and baseline dietary support. The aim is to achieve a total protein intake of 2.0 ± 0.2 g/kg/day, in accordance with cancer nutrition guidelines. This intervention is designed to evaluate whether high-dose protein supplementation reduces the incidence and severity of radiation-induced oral mucositis and improves serum prealbumin levels in head and neck cancer patients.

ControlDIETARY_SUPPLEMENT

An isocaloric placebo oral supplement that matches the protein supplement in appearance, taste, volume (200mL), and frequency of administration. The placebo contains no protein or amino acids and provides equivalent caloric content through carbohydrates. It is administered daily throughout the course of radiotherapy, alongside standard nutritional counseling and baseline dietary support (20-25 kcal/kg/day and 1-1.2 g protein/kg/day). This intervention is used to control for the effects of additional caloric intake, isolating the impact of supplemental protein on clinical outcomes.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age 18-75 years * Histologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx * No distant metastases (M0 stage) * Planned to receive curative or postoperative radiotherapy (with or without concurrent therapy) with a mean oral cavity dose ≥20 Gy * Adequate nutritional intake via oral or nasogastric route * Willingness to follow NCCN/MASCC guidelines for oral care during radiotherapy * Signed written informed consent Exclusion Criteria: * PG-SGA score ≥8 (indicating severe nutritional risk) * Use of non-guideline-recommended oral care during radiotherapy * Use of other protein supplementation products during radiotherapy * Known allergy to components of the study product * Acute or chronic renal insufficiency * Severe hepatic impairment * Congestive heart failure requiring fluid restriction * Gastrointestinal disorders affecting amino acid absorption (e.g., atrophic gastritis, bowel obstruction, inflammatory bowel disease) * Conditions increasing aspiration risk (e.g., abdominal compartment syndrome, gastric emptying disorders) * Inborn errors of amino acid metabolism * Cognitive impairment, psychiatric illness, or other factors affecting compliance or informed consent

Outcomes

Primary Outcomes

Change in Serum Prealbumin Levels

Change in serum prealbumin (PAB) levels from baseline to the end of radiotherapy. Blood samples will be collected before the initiation of radiotherapy and at the completion of treatment. The difference will be calculated to assess the nutritional effect of the protein supplement.

Time frame: Baseline to end of radiotherapy (approximately 6-8 weeks)

Incidence of Grade ≥3 Radiation-Induced Oral Mucositis

The number and proportion of participants who develop Grade 3 or higher acute oral mucositis during or within 3 months after radiotherapy, assessed according to the Radiation Therapy Oncology Group (RTOG) Acute Radiation Morbidity Scoring Criteria.

Time frame: From the start of radiotherapy to 3 months post-radiotherapy

Secondary Outcomes

Time to Resolution of Grade ≥3 Oral Mucositis

The number of days from the onset of Grade ≥3 radiation-induced oral mucositis to its resolution to Grade 1 or lower, based on RTOG criteria.

Time frame: From onset of mucositis to recovery or 3 months post-radiotherapy

Change in Body Weight During Radiotherapy

The difference in body weight from baseline to the end of radiotherapy, used as a proxy for nutritional status and treatment tolerance.

Time frame: Baseline to end of radiotherapy (approximately 6-8 weeks)

Change in Quality of Life Score: EORTC QLQ-C30

Change in patient-reported quality of life, assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), from baseline to the end of radiotherapy. Scores are linearly transformed to a 0 to 100 scale. For the global health status and functional scales, higher scores indicate better quality of life or functioning; for the symptom scales/items, higher scores indicate greater symptom burden.

Time frame: Baseline, during radiotherapy, and at end of radiotherapy

Change in Head and Neck Cancer-Specific Quality of Life Score: EORTC QLQ-H&N35

Change in patient-reported head and neck cancer-specific quality of life, assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Cancer Module (EORTC QLQ-H\&N35), from baseline to the end of radiotherapy. Scores are linearly transformed to a 0 to 100 scale, with higher scores indicating worse symptoms or problems.

Time frame: Baseline, during radiotherapy, and at end of radiotherapy

Incidence of Adverse Events

Occurrence of treatment-related adverse events, including gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain) and other acute toxicities, assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

Time frame: From start of radiotherapy through 3 months post-radiotherapy

Incidence of Serious Adverse Events

Serious adverse events are defined as events that result in death, are life-threatening, require inpatient hospitalization or prolongation of existing hospitalization, result in persistent or significant disability/incapacity, or are otherwise medically important.

Time frame: From start of radiotherapy through 3 months post-radiotherapy

Opioid Usage for Oral Pain Control

Total cumulative dose of opioid analgesics used by participants during the study period to control oral pain due to mucositis, recorded and analyzed as an indicator of symptom severity.

Time frame: From start of radiotherapy to end of treatment (approximately 6-8 weeks)