Impact of the Use of Zinc in the Prevention of Oral Mucositis in Pediatric Patients With Lymphoblastic Acute Leukemia.

Study Overview
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Brief Summary
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Oral mucositis (OM) is a secondary complication of chemo/radiotherapy, which causes pain, dysphagia and predisposition to infections, being a frequent reason for hospitalization that may have an impact on the prognosis of cancer patients. Various interventions for the prevention of OM have been studied, including the use of zinc, which is a micronutrient that participates in various cellular functions and in wound repair, while showing a reduction in the incidence and severity of MO, so the purpose of the present study is to evaluate the impact of the use of zinc in the prevention of oropharyngeal mucositis in pediatric patients with acute lymphoblastic leukemia in chemotherapy, comparing it with the use of placebo. Hypothesis: The use of zinc reduces the incidence and severity of OM in pediatric patients with ALL in chemotherapy compared to the control group.

Detailed Description
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Objective: To evaluate the impact of the use of zinc in the prevention, incidence and severity of oral mucositis in patients with acute lymphoblastic leukemia in chemotherapy (induction and consolidation phase) of the National Institute of Pediatrics and the Federico Gómez Children's Hospital of Mexico during the period from 2019 to 2020. Methodology: Double-blind randomized clinical trial conducted in pediatric patients with newly diagnosed or relapsed acute lymphoblastic leukemia. The subjects will be randomized to designate them in the control group (Group1 placebo) or intervention group (Group 2 zinc). The zinc / placebo intervention will be administered orally in tablets of 50-100 mg / day, from day 1 of chemotherapy until the end of the consolidation phase (2 to 2.5 months). For the detection of OM the mucositis scale of the World Health Organization will be used and the observation times will correspond to day 1, 4, 7, 14 and 21 of each chemotherapy cycle. Patients of both groups with OM will receive the same treatment (mouthwash of Gelclair) and will be observed daily until healing to determine the days of recovery. Statistical analysis: Independent t-test and Chi-square test for the difference between the two study groups, ANOVA to compare the groups with respect to the severity of OM.

Official Title
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Impact of the Use of Zinc in the Prevention of Oral Mucositis in Pediatric Patients With Lymphoblastic Acute Leukemia.

Conditions
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Oral Mucositis

Intervention / Treatment
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* Drug: Zinc Sulfate 50 Mg Tab
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 3 to 18 years Patients with recent diagnosis of ALL or relapse Pacientes who accept by informed consent to participate in the study. Exclusion Criteria: Patients with another disease or systemic condition in addition to ALL. Patients with Down syndrome Patients allergic to zinc or mannitol.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The subjects will be randomized to designate them in the control group (Group1 placebo) or intervention group (Group 2 zinc). The zinc / placebo intervention will be administered orally in tablets of 50-100 mg / day, from day 1 of chemotherapy until the end of the consolidation phase (2 to 2.5 months).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group1<br>Control | Drug: Placebo oral tablet<br>* The tablets were manufactured specifically for this study.<br>* Other names: Manitol;|
| Experimental: Group 2<br>Intervention (Zinc) | Drug: Zinc Sulfate 50 Mg Tab<br>* The tablets were manufactured specifically for this study.<br>* Other names: Zinc;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of oral mucositis | Presence /absence The presence of oral mucositis will be measured in all patients during the induction and consolidation phase of chemotherapy. | Participants will be followed for the duration of the induction and cosolidation phase of chemotherapy, an expected average of 2 to 2.5 months. | 
| Oral mucositis grade | World Health Organization (WHO) Criteria of Oral Mucositis The total score of this scale ranges from 0 to 4. Grade 0: no changes in the oral cavity are detected. Grade I: pain and erythema in mucosa, gums, tongue or palate. Grade II: erythema and ulcers, still with a solid diet tolerance. grade III: oral ulcers, tolerance to pasty foods and liquid diets. Grade IV: ulcers, erythema, pain, inability to swallow fluids, impossible oral feeding, and narcotic requirement to relieve pain. | Day 1 oral mucositis start to healing (1-14 days). | 
| Pain intensity: Visual analog scale | Visual analog scale Analogous visual scale of facial expressions, which is used in children 3 years and older. It is made up of faces with different expressions that represent a person who is happy because they do not feel pain or who is sad because they feel some pain or a lot of pain. A score is assigned to each face. The patient is asked to select the face that best describes how he feels. It will be recorded by the numerical score and will then be coded as follows: 0-2 No pain 3-4 Mild 5-6 Moderate 7-8 Intense 9-10 Maximum | Day 1 oral mucositis start to healing (1-14 days). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of opportunistic oral infections | Clinical or laboratory test. Record of suggestive lesions by C. albicans and determination by means of KOH, suggestive lesions of herpes and determination by PCR, suggestive bacterial lesions and detection through cultures. 0. Absent Fungal Bacterial Viral | Day 1, 4, 7, 14 and 21 of the induction and consolidation phase. | 
| Neutropenia | Absolute neutrophil count obtained by laboratory test (blood count). 0. Absence of neutropenia Mild: 1,000-1,500 / ml Moderate: 500-1,000 / ml Severe: <500 / ml | During the induction and consolidation phase. Day 1, 4, 7, 14 and 21 of each phase. (2 to 2.5 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zinc, Leukemia, Acute Lymphoblastic