Trial Title:
Efficacy of Glutamine in Management of Radiation Mucositis
NCT ID:
NCT05856188
Condition:
Radiation-Induced Mucositis
Conditions: Official terms:
Mucositis
Conditions: Keywords:
glutamine, Oral Mucositis, Salivary TGF b1
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Triple (Participant, Care Provider, Investigator)
Intervention:
Intervention type:
Dietary Supplement
Intervention name:
Glutamine
Description:
Biologic
Arm group label:
Group I (Test group):
Arm group label:
Group II (Control group)
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:
1. Is glutamine effective in management of Radiation Induced Mucositis?
2. 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.
Criteria for 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
Gender:
All
Minimum age:
20 Years
Maximum age:
70 Years
Healthy volunteers:
Accepts Healthy Volunteers
Locations:
Facility:
Name:
ain shams University
Address:
City:
Cairo
Zip:
11565
Country:
Egypt
Status:
Recruiting
Contact:
Last name:
hani wlliam, MD
Phone:
+20 0001000093885
Email:
ethicscommittee.fdasurec@gmail.com
Facility:
Name:
Fatma E.Sayed
Address:
City:
Cairo
Country:
Egypt
Status:
Recruiting
Contact:
Last name:
Fatma E.Sayed, MD
Phone:
+20 0001000093885
Email:
haniwelliam@gmail.com
Start date:
January 1, 2022
Completion date:
August 1, 2023
Lead sponsor:
Agency:
Ain Shams University
Agency class:
Other
Source:
Ain Shams University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05856188
