Clinical trial NCT04488237: Vitamin D and Methotrexate Adverse Effects
Official title: Effect of Vitamin D Administration on Methotrexate Adverse Effects in Patients With Acute Lymphoblastic Leukemia
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Lymphoblastic Leukemia
Keywords: methotrexate
vitamin D
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2020-07-27
Enrollment: 50
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: cases include patients with acute leumphoblastic leukemia recieving methotrexate in treatment protocol

Brief summary: Since methotrexate toxicity represents a major problem in patients treating with cancer and there are few studies about the role of vitamin D in the pathogenesis of this toxicity, so the aim of the present study is investigation of the effect of vitamin D administration on methotrexate toxicity such as oral ulcerations, bone marrow toxicity as well as renal and hepatic toxicity also the role of inflammatory mediators and oxidative stress markers in methotrexate toxicity will be evaluated, taking in consideration the dose of leucovorin rescue.

Detailed description: Leukemia is a type of blood cancer that affects the body's white blood cells (WBCs). White blood cells help fight infection and protect the body against disease, but in leukemia, some of the white blood cells turn cancerous and don't work as they should. As more cancerous cells form in the blood and bone marrow (spongy tissue inside the bones), there's less room for healthy cells .

The different types of leukemia can be either acute (fast growing) or chronic (slow growing). Acute lymphoblastic leukemia (ALL) happens when the body makes too many lymphoblasts (a type of white blood cell). It's the most common type of childhood cancer.

Treatment outcome of acute leukemia has been improved recently using Methotrexate . Side effects of methotrexate usually in the form of ulcerative stomatitis, leukopenia (lower amount of white blood cells), nausea, abdominal discomfort, and elevated liver and kidney function tests. Identifying risk factors leading to these side effects would be valuable to develop preventive interventions and improve quality of life for these young patients.

Studies revealed a relationship between vitamin D deficiency and adverse reactions of chemotherapy in cancer patients. This vitamin is important in many physiological processes in the body as bone mineralization and immune regulations . A human body produces vitamin D as a response to sun exposure. A person can also boost their vitamin D intake through certain foods or supplements. .

Previous literature showed that receptors for vitamin D expressed in the mucosa and so there is a relationship between vitamin D deficiency and increase inflammation and impairment of mucosa .

Vitamin D is a fat-soluble vitamin that not only regulates calcium absorption and bone metabolism, but can also regulate cell proliferation, differentiation and the immune response, vitamin D insufficiency/deficiency is associated with poor clinical outcome and significantly worse progression free survival of patients from leukemia and lymphoma.

Calcium is the most abundant element in the human body and is essential for life. It has a key role in many physiological processes including skeletal mineralization, muscle contraction, nerve impulse transmission, blood clotting, and hormone secretion . 1, 25-Dihydroxyvitamin D3 the active form of vitamin D plays major role in intestinal calcium absorption, Calcium homeostasis is also regulated by parathyroid hormone.

Patients with acute lymphoblastic leukemia may be at risk of vitamin D deficiency because of impaired vitamin intake and sunlight exposure .

Eligibility criteria: Inclusion Criteria:

1. Patients with acute lymphoblastic leukemia who do not start treatment course with methotrexate.
2. Both sex will be included.
3. Age group (1 -12 years)

Exclusion Criteria:

1. Patients with other type of cancer beside ALL.
2. Patients with renal, hepatic or hematological diseases.

Primary outcomes:
measure: Effect of vitamin D administration on methotrexate adverse effects in patients with acute lymphoblastic leukemia
timeFrame: 1 to 2 years according to the availability of the cases
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Mahmoud Hamdy Abdel-Raheem, Phd
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Mohammed Mostafa Elbadr, Phd
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Nivin Abdel-Azim Abdel-Rehim, Phd
role: STUDY_DIRECTOR
References:
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citation: Oosterom N, Dirks NF, Heil SG, de Jonge R, Tissing WJE, Pieters R, van den Heuvel-Eibrink MM, Heijboer AC, Pluijm SMF. A decrease in vitamin D levels is associated with methotrexate-induced oral mucositis in children with acute lymphoblastic leukemia. Support Care Cancer. 2019 Jan;27(1):183-190. doi: 10.1007/s00520-018-4312-0. Epub 2018 Jun 19.
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citation: Fakih MG, Trump DL, Johnson CS, Tian L, Muindi J, Sunga AY. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int J Colorectal Dis. 2009 Feb;24(2):219-24. doi: 10.1007/s00384-008-0593-y. Epub 2008 Oct 2.