Effect of Arginine and Glutamine on Radiation-induced Oral Mucositis: a Trible Blinded Randomized Controlled Clinical Trial

NCT06764420 | Completed

• 1 other identifier: (21)/7-2024
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Oral Mucositis (OM) is a painful inflammation and ulceration of the oral mucosa, often resulting from cancer treatments like chemotherapy and radiation therapy, particularly in head and neck cancer patients. This condition is highly prevalent, affecting up to 40% of patients undergoing conventional chemotherapy, 80% of those receiving high-dose chemotherapy before hematopoietic stem cell transplantation, and nearly all patients undergoing radiation therapy for head and neck cancers. OM develops in four phases: inflammatory/vascular, epithelial, ulcerative/bacteriological, and wound healing. The initial phase involves damage to DNA and basal epithelial cells due to free radicals and reactive oxygen species (ROS) produced by treatments. This damage leads to a cascade of inflammatory reactions, resulting in visible lesions and bacterial colonization in the subsequent stages. Glutamine, an amino acid abundant in human blood, plays a crucial role in cellular repair, immune function, and muscle maintenance. It is a preferred energy source for lymphocytes and the gastrointestinal tract, aiding in mucosal healing and resistance to infections. Studies suggest that glutamine supplementation can reduce the toxic effects of radiation on the GI tract and improve mucosal healing by supporting immune cells and reducing inflammation. L-arginine, another amino acid, contributes to protein synthesis, nitric oxide production, and regulation of various physiological functions. It has been shown to decrease intestinal inflammation and oxidative stress, promoting mucosal immune homeostasis. L-arginine administration has demonstrated beneficial effects in reducing intestinal injury and inflammation in experimental models. The study proposes evaluating the combined effect of arginine and glutamine on radiation-induced mucositis in head and neck cancer patients. The primary objective is to assess the clinical efficacy of an oral suspension of these amino acids using the WHO Oral Toxicity Scale. Secondary objectives include evaluating pain and mucositis severity using assessment scales. The hypothesis is that arginine and glutamine supplementation may reduce mucositis severity and improve clinical outcomes, potentially leading to better nutritional status, enhanced survival, and reduced complications in cancer patients. This study aims to fill the gap in existing research by investigating the synergistic effects of these amino acids in managing radiation-induced mucositis.

Conditions

Radiation Mucositis; Head and Neck Cancer

Keywords

arginine; glutamine; HNC; Mucositis; Radiation

Outcome Measures

Primary Outcomes (1)

• World Health Organization (WHO) Oral Toxicity Scale for grading oral mucositis.

  World Health Organization (WHO) Oral Toxicity Scale for grading oral mucositis. description? The World Health Organization (WHO) Oral Toxicity Scale is a standardized tool used to grade the severity of oral mucositis, which is a common side effect of cancer treatments like chemotherapy and radiotherapy. The scale helps clinicians assess and document the extent of mucositis in patients, ensuring consistent reporting and comparison across studies. Grade 0 No mucositis; normal oral mucosa. Grade 1 Soreness and erythema (redness) but no ulcers. Grade 2 Erythema and ulcers present, but the patient can still tolerate a solid diet. Grade 3 Ulcers are present, and the patient can only tolerate a liquid diet. Grade 4 Ulcers are present, and the patient cannot tolerate any oral intake (solids or liquids)

  Baseline (before the start of radiotherapy), second week of radiotherapy, seventh week of radiotherapy, and three months after the completion of radiotherapy.

Secondary Outcomes (1)

• Oral Mucositis Assessment Scale (OMAS) Score

  Baseline (before the start of radiotherapy), second week of radiotherapy, seventh week of radiotherapy, and three months after the completion of radiotherapy.

Other Outcomes (1)

• Pain Visual Analog Scale (VAS)

  Baseline (before the start of radiotherapy), second week of radiotherapy, seventh week of radiotherapy, and three months after the completion of radiotherapy.

Study Arms (2)

Intervention Group

EXPERIMENTAL

This group includes twenty patients receiving a combined oral suspension of 5 grams of arginine and 5 grams of glutamine dissolved in cold water. The suspension is taken 30 minutes before meals, three times per day, through the swish and swallow technique throughout the radiotherapy period. This group aims to evaluate the effectiveness of the combined treatment in managing radiation-induced mucositis.

Dietary Supplement: Arginine and Glutamine Oral Suspension

Control Group

ACTIVE COMPARATOR

This group includes twenty patients receiving an oral suspension of 5 grams of glutamine dissolved in cold water. The suspension is taken 30 minutes before meals, three times per day, through the swish and swallow technique throughout the radiotherapy period. This group serves as a control to compare the efficacy of glutamine alone with the combined treatment in managing radiation-induced mucositis. General measures and analgesic drugs according to the WHO scale are also provided.

Dietary Supplement: Glutamine Oral Suspension

Interventions

Glutamine Oral Suspension DIETARY_SUPPLEMENT

Participants in this group will receive an oral suspension containing 5 grams of glutamine dissolved in cold water. This solution is administered 30 minutes before meals, three times per day, using the swish and swallow technique throughout the radiotherapy period. This control intervention serves to compare the effects of glutamine alone with the combined arginine and glutamine treatment. In addition to the glutamine suspension, patients in this group will receive general measures and analgesic drugs according to the WHO scale to manage symptoms of mucositis.

Control Group

Arginine and Glutamine Oral Suspension DIETARY_SUPPLEMENT

Participants in this group will receive an oral suspension containing 5 grams of arginine and 5 grams of glutamine dissolved in cold water. This solution is administered 30 minutes before meals, three times per day, using the swish and swallow technique throughout the radiotherapy period. The swish and swallow technique involves patients swishing the solution around the oral mucosa to ensure even distribution before swallowing. This intervention aims to evaluate the combined effect of arginine and glutamine on reducing the severity of radiation-induced mucositis, improving mucosal healing, and providing symptomatic relief.

Intervention Group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed histologic diagnosis of H\&N malignancy.
• Undergoing non-palliative radiotherapy in the oral cavity.
• Receiving radiation therapy with IMRT or 3D techniques. Received 50-70 Gy of total radiation at 2 Gy/fraction daily, 5 fractions/week. Concurrent chemotherapy with radiotherapy. Presence of Oral Mucositis. Age 20-70 years. Willingness to participate and complete study assessments.

You may not qualify if:

• Confirmed or medically treated diabetes mellitus. Radiotherapy within the last 6 months. Vulnerable patients.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ahmed Maher Teaching Hospital

Cairo, Cairo Governorate, 11277, Egypt

Location

Related Publications (1)

• Hassanein FEA, Mikhail C, Elkot S, Abou-Bakr A. L-arginine vs. L-glutamine oral suspensions for radiation-induced oral mucositis: a triple-blind randomized trial. J Cancer Res Clin Oncol. 2025 Jul 3;151(7):198. doi: 10.1007/s00432-025-06213-x.

  PMID: 40603739 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms; Mucositis

Interventions

Arginine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant professor

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: January 8, 2025
• Study Start: May 20, 2023
• Primary Completion: June 20, 2024
• Study Completion: September 20, 2024
• Last Updated: January 8, 2025

Record last verified: 2025-01

Locations

EG (1)