Clinical trial NCT04321850: Impact of the Use of Zinc in the Prevention of Oral Mucositis in Pediatric Patients With Lymphoblastic Acute Leukemia.
Official title: Impact of the Use of Zinc in the Prevention of Oral Mucositis in Pediatric Patients With Lymphoblastic Acute Leukemia.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Oral Mucositis
Keywords: Zinc
Leukemia, Acute Lymphoblastic
Lead sponsor: National Institute of Pediatrics, Mexico
Sponsor class: OTHER_GOV
Collaborators: name: Hospital Infantil de Mexico Federico Gomez
First posted: 2020-03-25
Enrollment: 21
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of oral mucositis
timeFrame: Participants will be followed for the duration of the induction and cosolidation phase of chemotherapy, an expected average of 2 to 2.5 months.
measure: Oral mucositis grade
timeFrame: Day 1 oral mucositis start to healing (1-14 days).
measure: Pain intensity: Visual analog scale
timeFrame: Day 1 oral mucositis start to healing (1-14 days).
Secondary outcomes:
measure: Presence of opportunistic oral infections
timeFrame: Day 1, 4, 7, 14 and 21 of the induction and consolidation phase.
measure: Neutropenia
timeFrame: During the induction and consolidation phase. Day 1, 4, 7, 14 and 21 of each phase. (2 to 2.5 months)
Other outcomes:
Locations:
city: Mexico
country: Mexico
facility: Marta M. Zapta Tarrés
Study officials:
affiliation: National Institute of Pediatrics
name: Marta M Zapata, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Federico Gomez Children's Hospital of Mexico
name: Luis E Juárez, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lowal KA, Alaizari NA, Tarakji B, Petro W, Hussain KA, Altamimi MA. DENTAL CONSIDERATIONS FOR LEUKEMIC PEDIATRIC PATIENTS: AN UPDATED REVIEW FOR GENERAL DENTAL PRACTITIONER. Mater Sociomed. 2015 Oct;27(5):359-62. doi: 10.5455/msm.2015.27.359-362. Epub 2015 Oct 5.
citation: Tian X, Chen WQ, Liu XL, Pi YP, Chen H. Efficacy and safety of oral zinc sulfate in the prevention of chemotherapy-induced oral mucositis: Protocol for a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2018 May;97(21):e10839. doi: 10.1097/MD.0000000000010839.
citation: Rambod M, Pasyar N, Ramzi M. The effect of zinc sulfate on prevention, incidence, and severity of mucositis in leukemia patients undergoing chemotherapy. Eur J Oncol Nurs. 2018 Apr;33:14-21. doi: 10.1016/j.ejon.2018.01.007. Epub 2018 Feb 2.
citation: Miller MM, Donald DV, Hagemann TM. Prevention and treatment of oral mucositis in children with cancer. J Pediatr Pharmacol Ther. 2012 Oct;17(4):340-50. doi: 10.5863/1551-6776-17.4.340.
citation: He M, Zhang B, Shen N, Wu N, Sun J. A systematic review and meta-analysis of the effect of low-level laser therapy (LLLT) on chemotherapy-induced oral mucositis in pediatric and young patients. Eur J Pediatr. 2018 Jan;177(1):7-17. doi: 10.1007/s00431-017-3043-4. Epub 2017 Nov 11.
citation: Sangthawan D, Phungrassami T, Sinkitjarurnchai W. A randomized double-blind, placebo-controlled trial of zinc sulfate supplementation for alleviation of radiation-induced oral mucositis and pharyngitis in head and neck cancer patients. J Med Assoc Thai. 2013 Jan;96(1):69-76.
citation: Mehdipour M, Taghavi Zenoz A, Asvadi Kermani I, Hosseinpour A. A comparison between zinc sulfate and chlorhexidine gluconate mouthwashes in the prevention of chemotherapy-induced oral mucositis. Daru. 2011;19(1):71-3.
citation: Hayashi H, Kobayashi R, Suzuki A, Yamada Y, Ishida M, Shakui T, Kitagawa J, Hayashi H, Sugiyama T, Takeuchi H, Tsurumi H, Itoh Y. Preparation and clinical evaluation of a novel lozenge containing polaprezinc, a zinc-L-carnosine, for prevention of oral mucositis in patients with hematological cancer who received high-dose chemotherapy. Med Oncol. 2016 Aug;33(8):91. doi: 10.1007/s12032-016-0795-z. Epub 2016 Jul 14.
citation: Arbabi-kalati F, Arbabi-kalati F, Deghatipour M, Ansari Moghadam A. Evaluation of the efficacy of zinc sulfate in the prevention of chemotherapy-induced mucositis: a double-blind randomized clinical trial. Arch Iran Med. 2012 Jul;15(7):413-7.
citation: Mansouri A, Hadjibabaie M, Iravani M, Shamshiri AR, Hayatshahi A, Javadi MR, Khoee SH, Alimoghaddam K, Ghavamzadeh A. The effect of zinc sulfate in the prevention of high-dose chemotherapy-induced mucositis: a double-blind, randomized, placebo-controlled study. Hematol Oncol. 2012 Mar;30(1):22-6. doi: 10.1002/hon.999. Epub 2011 Jun 21.