The Effect of Alpha Lipoic Acid on the Incidence and Severity of Radiotherapy-Induced Oral Mucositis in Head and Neck Cancer Patients

Study Overview
=================
Brief Summary
-----------------
A prospective, randomized, controlled, single-blinded study will be conducted at Clinical Oncology department, Ain Shams University Hospitals, assessing the effect of Alpha Lipoic Acid on the incidence and severity of radiotherapy induced oral mucositis in Head and Neck cancer patients.

Detailed Description
-----------------
All patients presenting to the Clinical Oncology department, Ain Shams University Hospitals, will be assessed for eligibility as follow: Inclusion criteria: Age >18 years. Diagnosis of stage I, II, III or IV squamous cell carcinoma, nasopharyngeal carcinoma. Measurable disease on CT scan at baseline. Planned to receive radiotherapy with a total dose 60 grays or more divided on 30 fractions with or without cisplatin (100 mg/m2, administered intravenously every 21 days for three cycles or 40 mg/m2 administered weekly for up to 7 weeks). Adequate liver function (liver transaminases level < 3 times upper normal limits and total bilirubin < 1.5 times upper normal limits). Adequate kidney function (estimated glomerular filtration rate >60 ml/min). Adequate bone marrow function (WBCs count > 3000 cells/mm3, ANC count >1500 cells/mm3 and platelets count > 100,000 cells/mm3). Exclusion criteria: Patients will be excluded if they have any of the following: Diagnosis of Thyroid cancer. Presence of other primary cancers. Treatment with alpha lipoic acid for any other indication. Allergy to alpha lipoic acid. Pregnant or lactating women. Eligible patients will be randomized to either… Alpha Lipoic Acid Group (intervention group): 35 patients will receive radiation therapy with or without platinum-based chemotherapy in addition to alpha lipoic acid 600 mg tablets twice daily (throughout the radiotherapy period). The medication will be brought from EVA company ( an Egyptian drug company ) under the trade name of thiotacid 600 mg tablets. Control Group: 35 Patients will receive radiation therapy with or without platinum-based chemotherapy plus placebo tablets of thiotacid throughout the radiation period All patients will be followed up weekly to assess the incidence and severity of radiation induced oral mucositis using the radiotherapy oncology group criteria also blood samples will be drawn at baseline , after three weeks (middle of radiation period) at the end of radiation period to asses changes in CRP and TAC levels

Official Title
-----------------
The Effect of Alpha Lipoic Acid on the Incidence and Severity of Radiotherapy-Induced Oral Mucositis in Head and Neck Cancer Patients

Conditions
-----------------
Radiation-Induced Mucositis

Intervention / Treatment
-----------------
* Drug: Alpha Lipoic Acid 600 MG Oral Tablets
* Other: Placebo tablets
* Radiation: radiation or concurrent chemoradiation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • Age >18 years. Diagnosis of stage I, II, III or IV squamous cell carcinoma, nasopharyngeal carcinoma. Measurable disease on CT scan at baseline. Planned to receive radiotherapy with a total dose 60 grays or more divided on 30 fractions with or without cisplatin (100 mg/m2, administered intravenously every 21 days for three cycles or 40 mg/m2 administered weekly for up to 7 weeks). Adequate liver function (liver transaminases level < 3 times upper normal limits and total bilirubin < 1.5 times upper normal limits). Adequate kidney function (estimated glomerular filtration rate >60 ml/min). Adequate bone marrow function (WBCs count > 3000 cells/mm3, ANC count >1500 cells/mm3 and platelets count > 100,000 cells/mm3). Exclusion Criteria: ● Diagnosis of Thyroid cancer. Presence of other primary cancers. Treatment with alpha lipoic acid for any other indication. Allergy to alpha lipoic acid. Pregnant or lactating women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective, randomized, controlled, single blinded study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alpha Lipoic Acid Group (intervention group)<br>35 patients will receive radiation therapy with or without platinum-based chemotherapy in addition to alpha lipoic acid 600 mg tablets twice daily (throughout the radiotherapy period). . | Drug: Alpha Lipoic Acid 600 MG Oral Tablets<br>* Alpha Lipoic Acid (ALA) is a drug which has been used in treatment of diabetic neuropathy . It act through enhancing nitric oxide-mediated endothelium-dependent vasodilation, thus improving microcirculation in patients with diabetic polyneuropathy. It is considered a safe drug, generally with a daily dose of 200 to 2400 mg/day is considered tolerable without significant side effects. Only gastrointestinal tracts side effects like nausea, vomiting, dyspepsia and abdominal pain have been described in some clinical trials. Also FDA experts confirm its safety and efficacy in humans<br>Radiation: radiation or concurrent chemoradiation<br>* radiation or concurrent radiotherapy plus platinum-based chemotherapy<br>|
| Placebo Comparator: Control Group<br>35 Patients will receive radiation therapy with or without platinum-based chemotherapy in addition to placebo tablets twice daily (throughout the radiotherapy period) | Other: Placebo tablets<br>* placebo tablets of the same generic of active drug which contain all the same ingredients as active tablets except alpha lipoic acid<br>Radiation: radiation or concurrent chemoradiation<br>* radiation or concurrent radiotherapy plus platinum-based chemotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of radiation induced oral mucositis | The patients will be followed up during the whole period of radiation and up to six weeks after radiation to evaluate the incidence and severity of radiation induced mucositis. Severity will be assessed by the oncologist using radiotherapy oncology group criteria (RTOG criteria) | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to develop grade III or IV radiation induced oral mucositis: | For each patient, the time from the start of radiotherapy till the development of grade III or IV RIOM will be recorded. | 4 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Head and Neck cancer, Alpha Lipoic Acid, Mucositis