Effect of Arginine- and Glutamine-based Oral Formulations on Salivary Biomarkers and Clinical Severity of Radiation-induced Oral Mucositis in Head and Neck Cancer: A Randomized Controlled Trial

NCT07020754 | Completed Phase 2

• 1 other identifier: FUE.REC25/8-2025
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

This triple-blinded, randomized controlled clinical trial investigates the effectiveness of L-arginine and L-glutamine oral suspensions in managing radiation-induced oral mucositis (RIOM) in patients with head and neck cancer (HNC) undergoing radiotherapy. A total of 69 patients are randomly assigned to three groups: L-arginine + maltodextrin, glutamine + maltodextrin, or maltodextrin alone (control). The interventions are administered as a swish-and-swallow solution three times daily from the second to seventh week of radiotherapy. Key outcomes assessed include oral mucositis severity (WHO scale), pain intensity (VAS), body mass index (BMI), oral health-related quality of life (OHIP-14), and salivary epidermal growth factor (EGF) levels. The study aims to determine whether L-arginine offers superior mucosal healing and symptom relief compared to glutamine or placebo.

Conditions

Oral Mucositis; Oral Mucositis Due to Radiation; Radiation Induced Oral Mucositis

Keywords

Radiation-induced oral mucositis (RIOM); Head and neck cancer (HNC); L-arginine; Epidermal growth factor (EGF); L-glutamine

Outcome Measures

Primary Outcomes (1)

• Change in salivary IL-6 levels during radiotherapy-induced oral mucositis

  Salivary interleukin-6 (IL-6) concentration will be measured using enzyme-linked immunosorbent assay (ELISA) to assess inflammatory response during radiotherapy. The primary endpoint is the between-group difference in IL-6 change from baseline to peak mucositis following arginine-, glutamine-, or maltodextrin-based oral intervention. IL-6 was selected as the primary biomarker due to its established role in radiation-induced oral mucosal inflammation and association with mucositis severity.

  From week 2 of radiotherapy (baseline) , week 5 of radiotherapy (peak mucositis phase, week 7 of RT

Secondary Outcomes (4)

• Change in Salivary Epidermal Growth Factor (EGF) Levels

  Baseline (2nd week of radiotherapy), week 5 of radiotherapy (peak mucositis phase) End of treatment (7th week)

• Change in salivary nitric oxide levels during radiotherapy-induced oral mucositis

  From week 2 of radiotherapy (baseline) to week 5 (peak mucositis) and week 7 (end of radiotherapy)

• Severity of Oral Mucositis

  2nd, 5th, and 7th weeks of radiotherapy

• Pain Intensity

  2nd, 5th, and 7th weeks of radiotherapy

Study Arms (3)

Group I - L-arginine + Maltodextrin Oral Suspension

EXPERIMENTAL

Patients receive 5 g of L-arginine + 5 g of maltodextrin dissolved in cold distilled water.

Dietary Supplement: L-arginine Oral Suspension

Group II - Glutamine + Maltodextrin Oral Suspension

ACTIVE COMPARATOR

Group II - Glutamine + Maltodextrin Oral Suspension

Dietary Supplement: L-glutamine Oral Suspension

Group III - Maltodextrin Oral Suspension (Control Group)

PLACEBO COMPARATOR

Patients receive 10 g of maltodextrin only, prepared and administered identically to the other groups.

Dietary Supplement: Maltodextrin Oral Suspension (Control)

Interventions

L-glutamine Oral Suspension DIETARY_SUPPLEMENT

Type: Dietary supplement Dosage: 5 g L-glutamine + 5 g maltodextrin Route: Oral (swish-and-swallow) Frequency: Three times daily, 30 minutes before meals Duration: From the 2nd to the 7th week of radiotherapy

Group II - Glutamine + Maltodextrin Oral Suspension

Maltodextrin Oral Suspension (Control) DIETARY_SUPPLEMENT

Type: Placebo comparator Dosage: 10 g maltodextrin Route: Oral (swish-and-swallow) Frequency: Three times daily, 30 minutes before meals Duration: From the 2nd to the 7th week of radiotherapy

Group III - Maltodextrin Oral Suspension (Control Group)

L-arginine Oral Suspension DIETARY_SUPPLEMENT

Type: Dietary supplement Dosage: 5 g L-arginine + 5 g maltodextrin Route: Oral (swish-and-swallow) Frequency: Three times daily, 30 minutes before meals Duration: From the 2nd to the 7th week of radiotherapy

Group I - L-arginine + Maltodextrin Oral Suspension

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 20 and 70 years
• Diagnosed with head and neck cancer (HNC) and undergoing radiotherapy (RT)
• Development of oral mucositis during the 2nd to 3rd week of RT
• Receiving a minimum radiation dose of 50 Gy to the oral cavity
• Undergoing intensity-modulated radiotherapy (IMRT) with three-dimensional conformal techniques after complete tumor resection
• Ability and willingness to provide informed consent
• Able to comply with study procedures and follow-up assessments

You may not qualify if:

• History of prior radiotherapy
• Diagnosed with diabetes mellitus
• Presence of salivary gland tumors
• Renal or hepatic insufficiency
• Sepsis or any active systemic infection
• Distant metastases
• Any condition that may interfere with oral sample collection or affect EGF levels (e.g., autoimmune oral disease)

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Faculty of Dentistry, Future University in Egypt

Cairo, Cairo Governorate, 10226, Egypt

Location

MeSH Terms

Conditions

Stomatitis; Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant professor

Study Record Dates

• First Submitted: June 6, 2025
• First Posted: June 13, 2025
• Study Start: April 1, 2025
• Primary Completion: January 1, 2026
• Study Completion: January 25, 2026
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

EG (1)