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Efficacy of Glutamine in Management of Radiation Mucositis

Primary Purpose

Radiation-Induced Mucositis

Status
Recruiting
Phase
Not Applicable
Locations
Egypt
Study Type
Interventional
Intervention
Glutamine
Sponsored by
Ain Shams University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Radiation-Induced Mucositis focused on measuring glutamine, Oral Mucositis, Salivary TGF b1

Eligibility Criteria

20 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: a) Patients with a confirmed histologic diagnosis of H&N malignancy who are referred to non-palliative radiotherapy in the oral cavity. b) Patient who is receiving radiation therapy with intensity modified radiotherapy IMRT or 3D techniques. c) Patients received 50-70 Gy of total radiation at the rate of 2 Gy/fraction daily and 5 fractions/week. d) Patient who received concurrent chemotherapy with radiotherapy e) Presence of Oral Mucositis f) Age 20-70 years old g) Willing to participate in the study h) Able to complete the study assessments Exclusion Criteria: a) Have a confirmed or medically treated diabetes mellitus25 b) Radiotherapy within the last 6 months prior to this study c) Vulnerable patients

Sites / Locations

  • ain shams UniversityRecruiting
  • Fatma E.SayedRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Group I (Test group):

Group II (Control group)

Arm Description

Will include twenty patients receiving Glutamine oral suspension (5 grams of glutamine and 5 g maltodextrin dissolved in cold water) 30 min before a meal, 3 times per day through swish and swallow technique25 throughout the radiotherapy period.

Included twenty patients receiving maltodextrin oral suspension (5 g maltodextrin dissolved in cold water) 30 min before a meal, 3 times per day through swish and swallow technique throughout the radiotherapy period along with general measures as well as analgesic drugs according to the WHO scale.

Outcomes

Primary Outcome Measures

Change from World Health Organization Oral Toxicity Scale Grading of Oral Mucositis during radiotherapy.
World Health Organization Oral Toxicity Scale Grading of Oral Mucositis ranges from "1,2,3,4) the grade1 means the least clinical sign and symptoms while grade 4 means the worst clinical sign and symptoms of mucositis.
Change in the level of salivary transforming growth factor beta 1 during radiotherapy.
salivary level of transforming growth factor beta 1 assessment using enzyme linked immune assay may range from 10-4000ng/L

Secondary Outcome Measures

Change in Pain visual analog scale during radiotherapy.
Pain visual analog scale range from (0 to 10 ), 0 means no pain felt, while 10 means the worst unbearable pain.

Full Information

First Posted
March 25, 2023
Last Updated
May 3, 2023
Sponsor
Ain Shams University
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1. Study Identification

Unique Protocol Identification Number
NCT05856188
Brief Title
Efficacy of Glutamine in Management of Radiation Mucositis
Official Title
Efficacy of Glutamine in Management of Radiation Induced Mucositis in Patients With Head and Neck Cancer (A Randomized Controlled Clinical Study)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2022 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
August 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ain Shams University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this [ type of study: Clinical trial] is to test effectiveness of glutamine in management of Radiation Induced Mucositis in head and neck cancer patients. The main question [s] ] is to [ learn about, test, compare etc.] it aims to answer are: Is glutamine effective in management of Radiation Induced Mucositis? Does Glutamine oral suspension affect the level of TGFβ1 in saliva of patients with radiation induced mucositis? participants will be asked to dissolve oral glutamine and maltodextrin in distalled water and swish and swallow three times daily during radiotherapy.
Detailed Description
Oral Mucositis (OM) refers to inflammation and ulceration of the oral mucosa as a side-effect of cancer therapy. OM and esophagitis can occur secondary to systemic chemotherapy for cancer, high-dose chemotherapy as a hematopoietic transplant preparative regimen or due to radiation therapy (RT) for head and neck (H&N) cancer or if the oropharynx or esophagus is in field during and after radiation of bone metastases. OM is a common problem and occurs in about 20-40% of patients receiving conventional chemotherapy for solid tumors, about 80% of patients receiving high dose chemotherapy prior to a hematopoietic stem cell transplantation (HSCT) and almost all patients receiving RT for H&N cancer. Ulcerative OM and esophagitis are extremely painful, with many patients needing systemic opioids such as morphine or fentanyl for pain management.1 Oral mucositis is an acute mucosal inflammation that starts as redness and progresses to an increased ulceration and pseudomembrane formation, which represent a temporary barrier until cellular repair promotes healing. The impaired mucosal tissue often permits bacteria and fungi to penetrate into damaged mucosa and cause infections.2 Mucositis is divided into 4 phases: an initial inflammatory/ vascular phase, an epithelial phase, an ulcerative/bacteriological phase, and a wound healing phase.3 In the initial stage, irradiation or chemotherapy, by producing free radicals and Reactive oxygen species (ROS), harmfully influences cells and strands of DNA in the basal epithelium and the submucosa and leads to lesions. ROS also activate transcription factors and leads to cell destruction in later stages. In the next stage, not only ROS but also damaged cells and DNA start a cascade of reactions. During these reactions, proinflammatory cytokines produce and lead to lesions and basal cell apoptosis. These products have a positive reaction as well, and strengthen the lesions. In this stage, the tissue appears to be normal, with only with slight erythema. In the third stage, painful lesions appear and are colonized by bacteria. Bacterial colonization can lead to the release of new pro-inflammatory cytokines. After stopping cancer treatment, oral mucositis vanishes little by little. In the healing process, symptoms decrease and the mucosa become normal, but outstanding neovascularization remains. This tissue is easily broken and it is susceptible to chemotherapy and/or radiotherapy in future periods of cancer treatments.4 . This diversity in scoring systems for Oral Mucositis may lead to controversies among studies. The most widely used measurements for oral mucositis are the World Health Organization(WHO) and Radiation Therapy Oncology Group (RTOG) scales as below. Also, the Oral Mucositis Assessment Scale, and a Visual Analog Pain Scale (patient reporting scale of 0-10) are used for grading of mucositis. Mucosal changes like redness, ulceration with functional outcomes such as inability to eat and pain have been assessed in these scales. Based on clinical examination, 4 distinct grades can be determined for mucositis from 0 to 4 scores. Higher grades of mucositis (grade 3-4) are associated with loss of taste, hemorrhage, decreased intake of food and fluids, ulceration, pain, loss of voice, and low quality of life.5 The biomarkers can be considered promising tools for prediction and evaluation of oral mucositis. Eight groups of biomarkers were analyzed: growth factors, cytokines, acute-phase inflammatory markers, genetic factors, general proteins, plasma antioxidants and apoptotic proteins.6 Growth factors are proteins released by individual cells to transmit messages to other cells and to stimulate cellular growth, proliferation, and differentiation.7 Regarding the epithelia growth factor (EGF), it was observed a decrease in EGF levels during RT and a trend to reduced EGF in patients with more severe OM.8 Another important growth factor analyzed was the transforming growth factorβ (TGFβ), which controls cellular homeostasis and proliferation, wound healing, immunosuppression, and angiogenesis.9 It was observed that a TGFβ1 level was significantly higher in patients experiencing severe radiation toxicity, confirming that damaged tissues contribute to higher plasma TGFβ1 level.10 Cytokines are also involved in RT-induced mucositis because they are released by disintegrating cells or by an immune reaction, resulting in the recruitment of inflammatory cells and in the development of toxicity.11 It was observed that the level of interleukins IL-6, IL-10 and IL-1 β seemed to be related to severe mucositis.12 Acute-phase inflammatory markers are also used as biomarkers to predict the risk for patients developing OM as a consequence of cancer treatment. C-reactive protein (CRP) is one of these markers, and it contributes to body defense by neutralizing inflammatory agents and it can be easily measured as a quantitative marker of inflammatory activity.13 It was demonstrated an increase of CRP and correlation between this increase and the progression of mucositis. It could only observe during the initial weeks of treatment.11 Erythrocyte Sedimentation Rate (ESR) is another important marker of the acute-phase inflammatory response, used to evaluate benign inflammatory conditions and neoplastic diseases. An increase in ESR levels during cancer treatment was observed, followed by a decrease in concentration of this biomarker. This variation was related to the grading of mucositis, which also initially increased in severity and then decreased towards the end of treatment.14 Glutamine is an L-alpha-amino acid. It is the most abundant free amino acid in human blood. Glutamine is needed for several functions in the body including for the synthesis of proteins as well as an energy source. Glutamine can be synthesized by the body and can also be obtained from the diet if needed.15 Glutamine is an important nitrogen donor in intracellular metabolism and in the maintenance of intestinal tract, immune cells, and muscle.16 Weight loss in cancer patients is common, but sarcopenia (loss of muscle mass) is associated with increased complications and significantly worse survival.17 Glutamine is a preferred fuel for both lymphocytes and gastrointestinal (GI) tract 18, thus it plays an important role in helping to defend against infections and to assist mucosa in being a barrier against infection. Glutamine has a central role in intracellular metabolism and acts as a nitrogen shuttle between muscle and other tissues; it is at a high and relatively stable concentration in plasma and red blood cells and at a much higher concentration in muscle compared to other amino acids.19 Since plasma glutamine concentrations are only minimally affected over time by either glutamine ingestion or infusion, muscle can be considered as a "bank" and the liver can be considered as the "banker".17 Neutrophils, macrophages, and lymphocytes are needed for mucosal barrier immune defenses. Since glutamine is fuel for leukocytes, topical/oral/enteral glutamine may contribute to mucosal healing by not only a direct effect on mucosal epithelial cells, but also by improvement in host mucosal immune function and ability to resist microbial invasion.16 Interestingly, resilience of lymphocyte recovery, as measured by absolute lymphocyte count (ALC) after the very first cycle of chemotherapy, has been associated with a better prognosis in a variety of malignancies including acute lymphoblastic leukemia as well as tumors such as osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma . It is possible that better nutrition, with amino acids including glutamine as fuel for lymphocytes, could contribute to ALC recovery and/or resilience. Animal models and human studies have shown glutamine supplementation improves the ability to resist the toxic effects of radiation to the GI tract.15 Detoxification and resilience to free radical damage by chemotherapy (e.g., doxorubicin or cyclophosphamide) and/or radiation of normal tissues and tumors can involve the antioxidant glutathione. Since glutamine is a substrate for glutathione synthesis, adequate mucosal cell glutamine may contribute towards improved healing after chemotherapy and radiation damage 20 as well as, interestingly, the simultaneous inhibition of glutathione levels in tumors, too.21 Furthermore, decreased inflammatory cytokines in normal cells and increased pro-apoptosis proteins in cancer cells were observed with glutamine + disaccharide supplementation. Thus, glutamine can contribute to selective improvement in host cell resilience, less inflammation, and decreased ability of tumors to detoxify chemotherapy or resist radiation, i.e. an improved therapeutic index of the anti-cancer therapy.22 Glutamine can be administrated by three common routes; parental, oral and topical through swishing. Topical oral swish and swallow glutamine has potential to ameliorate not only OM, but also esophagitis and enteritis after cancer chemotherapy and radiation. A small amino acid intervention may make a difference and possibly contribute to better overall nutritional status, improved survival with fewer complications, and ultimately less sarcopenia and lymphopenia.15 To the moment , there are no published studies regarding assessment of salivary TGFβ1 in glutamine treatment of radiotherapy induced mucositis So regarding the forementioned properties of glutamine, The hypothesis is to assess if the glutamine could affect severity of mucositis and the level of salivary TGFβ1. The purpose of this study is to evaluate the influence of glutamine in treatment of radiation induced mucositis in head and neck cancer patients and measuring the TGFβ salivary level before and after treatment with glutamine.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Radiation-Induced Mucositis
Keywords
glutamine, Oral Mucositis, Salivary TGF b1

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group I (Test group):
Arm Type
Experimental
Arm Description
Will include twenty patients receiving Glutamine oral suspension (5 grams of glutamine and 5 g maltodextrin dissolved in cold water) 30 min before a meal, 3 times per day through swish and swallow technique25 throughout the radiotherapy period.
Arm Title
Group II (Control group)
Arm Type
Placebo Comparator
Arm Description
Included twenty patients receiving maltodextrin oral suspension (5 g maltodextrin dissolved in cold water) 30 min before a meal, 3 times per day through swish and swallow technique throughout the radiotherapy period along with general measures as well as analgesic drugs according to the WHO scale.
Intervention Type
Dietary Supplement
Intervention Name(s)
Glutamine
Intervention Description
Biologic
Primary Outcome Measure Information:
Title
Change from World Health Organization Oral Toxicity Scale Grading of Oral Mucositis during radiotherapy.
Description
World Health Organization Oral Toxicity Scale Grading of Oral Mucositis ranges from "1,2,3,4) the grade1 means the least clinical sign and symptoms while grade 4 means the worst clinical sign and symptoms of mucositis.
Time Frame
Two points: -"baseline which is at the second week of radiotherapy" while -"the end of the radiotherapy is at seventh week of the radiotherapy or 4-5 weeks from baseline.
Title
Change in the level of salivary transforming growth factor beta 1 during radiotherapy.
Description
salivary level of transforming growth factor beta 1 assessment using enzyme linked immune assay may range from 10-4000ng/L
Time Frame
Two points: -"baseline which is at the second week of radiotherapy" while -"the end of the radiotherapy is at seventh week of the radiotherapy or 4-5 weeks from baseline.
Secondary Outcome Measure Information:
Title
Change in Pain visual analog scale during radiotherapy.
Description
Pain visual analog scale range from (0 to 10 ), 0 means no pain felt, while 10 means the worst unbearable pain.
Time Frame
Two points: -"baseline which is at the second week of radiotherapy" while -"the end of the radiotherapy is at seventh week of the radiotherapy or 4-5 weeks from baseline.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: a) Patients with a confirmed histologic diagnosis of H&N malignancy who are referred to non-palliative radiotherapy in the oral cavity. b) Patient who is receiving radiation therapy with intensity modified radiotherapy IMRT or 3D techniques. c) Patients received 50-70 Gy of total radiation at the rate of 2 Gy/fraction daily and 5 fractions/week. d) Patient who received concurrent chemotherapy with radiotherapy e) Presence of Oral Mucositis f) Age 20-70 years old g) Willing to participate in the study h) Able to complete the study assessments Exclusion Criteria: a) Have a confirmed or medically treated diabetes mellitus25 b) Radiotherapy within the last 6 months prior to this study c) Vulnerable patients
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fatma E Ahmed, professor
Phone
+20 0001000093885
Email
fatmaelsayed.fe@icloud.com
First Name & Middle Initial & Last Name or Official Title & Degree
hadeel G gamal, lecturer
Phone
00201017767662
Email
dr.hadeel@dent.asu.edu.eg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Suzan SA Ibrahim, professor
Organizational Affiliation
faculty of Dentistry- Ainshams university
Official's Role
Study Director
Facility Information:
Facility Name
ain shams University
City
Cairo
ZIP/Postal Code
11565
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
hani wlliam, MD
Phone
+20 0001000093885
Email
ethicscommittee.fdasurec@gmail.com
Facility Name
Fatma E.Sayed
City
Cairo
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fatma E.Sayed, MD
Phone
+20 0001000093885
Email
haniwelliam@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31612309
Citation
Arutla M, Raghunath M, Deepika G, Jakkampudi A, Murthy HVV, Rao GV, Reddy DN, Talukdar R. Efficacy of enteral glutamine supplementation in patients with severe and predicted severe acute pancreatitis- A randomized controlled trial. Indian J Gastroenterol. 2019 Aug;38(4):338-347. doi: 10.1007/s12664-019-00962-7. Epub 2019 Oct 14.
Results Reference
result
PubMed Identifier
7602720
Citation
Fahr MJ, Kornbluth J, Blossom S, Schaeffer R, Klimberg VS. Harry M. Vars Research Award. Glutamine enhances immunoregulation of tumor growth. JPEN J Parenter Enteral Nutr. 1994 Nov-Dec;18(6):471-6. doi: 10.1177/0148607194018006471.
Results Reference
result

Learn more about this trial

Efficacy of Glutamine in Management of Radiation Mucositis

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