Effectiveness of Hydrogen Water Intervention on Acute Oral Inflammation, Oral Microbiota, and Pain Following Free Flap Reconstruction in Patients With Oral Cancer

This study employs a Randomized Controlled Trial (RCT) design. Patients diagnosed with oral cancer by the attending physician and who meet the inclusion criteria will be admitted to the study after receiving a full explanation of the study objectives, intervention methods, potential risks, and participant rights from the research team upon their stable transfer to the plastic surgery ward post-operation. Written consent will be obtained from the patient and/or their legally authorized representative after adequate informed consent has been provided, before they are enrolled in the study.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Pain; Oral Cancer; Oral Squamous Cell Carcinoma (OSCC); Free Flap Reconstruction; Postoperative Oral Mucositis
• Intervention / Treatment: Other: Hydrogen Water Oral Care; Other: Water Oral Care

Detailed Description

The study adopts a Randomized Controlled Trial (RCT) design. Patients diagnosed with oral cancer by the attending physician and who meet the inclusion criteria are enrolled in the study upon their stable transfer from the Intensive Care Unit (ICU) to the plastic surgery ward post-operation.

The research team will personally explain the study objectives, intervention methods, potential risks, and participant rights to the subjects (and/or their legally authorized representatives) and provide written documentation. After addressing all questions, informed consent is obtained, and the subject is enrolled in the study.

Subjects are then assigned via computer-generated randomization at a 1:1 ratio. The experimental group (18 individuals) receives hydrogen-rich water oral care. The hydrogen-rich water is delivered daily after its concentration is measured.

Oral integrity is assessed using the Oral Assessment Guide (OAG), which includes 6 items: lips, tongue, saliva, oral mucosa, gums, and teeth, scored from 1 to 3 points. The minimum score is 6, and the maximum score is 18.

Oral care frequency is based on the OAG score:

6-10 points: Oral care once per shift. 11-14 points: Oral care once every 4 hours. 15-18 points: Oral care once every 2 hours. Oral care involves using a sponge toothbrush dipped in hydrogen-rich water (concentration 1.1 mg/L) to gently brush the mucosa, maxilla/mandible (upper/lower jaws), and tongue. This is continuously performed for 7 days.

The control group (18 individuals) receives plain boiled water for oral care, with the same frequency as the experimental group. The research team will daily record the subjects' compliance and any adverse reactions.

During the intervention period, both groups receive identical postoperative care and health education in the plastic surgery ward.

The research team will collect the first sample (pre-test, T0) when the patient is transferred from the ICU to the plastic surgery ward, and the second sample on the 7th day post-operation (T1). Saliva samples will be collected at both time points to evaluate oral inflammatory markers (such as IL-1$\beta$, IL-6, IL-10, TNF-α) and the oral microbiome (analyzed by RT-PCR detection of the 16S rRNA gene sequence)

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pi-Ling Chou, PhD; Phone Number: 2610 886-7-3121101; Email: piling.chou@gmail.com
• Study Contact Backup: Name: I-SHAN CHOU, MS; Phone Number: +886-917-520-113; Email: awoponn20@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed with oral cancer and receiving microsurgical free flap reconstruction.
• Age 18 years or older.
• Conscious and able to follow study instructions.
• Able to communicate without difficulty in Mandarin, Taiwanese, or through written communication.

Exclusion Criteria:

• Abnormal salivary gland function or severe xerostomia.
• Recent use of antibacterial mouthwash or antibiotic therapy that may affect oral microbiota.
• Presence of severe bacterial or viral oral infections, or significant periodontal disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrogen Water Oral Care Group; This study adopts a randomized controlled trial (RCT) design with an equal allocation pretest-posttest approach and double-blind methodology. Eligible patients who underwent microsurgical free flap reconstruction for oral cancer were enrolled once their postoperative condition stabilized. They were randomly assigned in a 1:1 ratio to the experimental group using a computer-generated randomization table. Immediately after allocation, the first saliva collection (T0) was performed. Participants in the experimental group received daily hydrogen water oral care, using hydrogen water with a concentration of 1.1 mg/L and a dissolution stability of at least 12 hours. A second saliva collection (T1) was conducted on Day 7 of the intervention to evaluate changes in salivary inflammatory biomarkers, oral microbiota, and pain.	Other: Hydrogen Water Oral Care; The research team provided hydrogen water daily according to group assignment. The hydrogen water used in this study contained 1.1 mg/L of dissolved hydrogen with a stability of no less than 12 hours. Participants performed oral care using the hydrogen water following standardized instructions. Saliva samples were collected at T0 (immediately after randomization) and T1 (Day 7 of the intervention) to assess changes in inflammatory markers, oral microbial composition, and pain levels during the intervention period.
Placebo Comparator: Water Oral Care Group; Patients assigned to the control group through the same computer-generated 1:1 randomization process received tap water oral care. The first saliva collection (T0) was completed immediately after group allocation. Participants in the control group performed oral care daily using tap water at time points and frequencies identical to those of the experimental group. The second saliva collection (T1) occurred on Day 7 of the intervention to compare the effects of different oral care solutions on changes in salivary inflammatory biomarkers, oral microbiota, and pain.	Other: Water Oral Care; The research team provided tap water for oral care daily, following the same procedures, frequency, and schedule as the experimental group, but without the active hydrogen component. Saliva samples were collected at T0 (immediately after randomization) and T1 (Day 7 of the intervention) to establish a placebo-controlled comparison of outcomes related to inflammatory markers, microbial profiles, and pain.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-1β、IL-6、IL-10、TNF-α	Salivary IL-1β、IL-6、IL-10、TNF-α concentration will be measured to assess the anti-inflammatory effect of hydrogen water oral care in postoperative oral cancer patients. Measurements will be used to evaluate changes in inflammation between baseline and Day 7.	Baseline (T0) and Day 7 (T1)
Oral Assessment Guide (OAG) Score	Change in total OAG score from baseline to Day 7 will be used to evaluate oral mucosal integrity.	Baseline (T0) and Day 7 (T1)

Collaborators and Investigators

• Sponsor: Kaohsiung Medical University Chung-Ho Memorial Hospital
• Investigators: Principal Investigator: I-SHAN CHOU, MS, Kaohsiung Medical University Chung-Ho Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: December 7, 2025
• First Submitted That Met QC Criteria: December 25, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Oral cancer; Pain assessment; Salivary Biomarkers; Hydrogen water; Free flap reconstruction
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Mouth Diseases; Stomatognathic Diseases; Postoperative Complications; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Pain, Postoperative; Mouth Neoplasms
• Other Study ID Numbers: KMUHIRB-F(II)-20250332

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