Vitamin D and Methotrexate Adverse Effects

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Effect of Vitamin D Administration on Methotrexate Adverse Effects in Patients With Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04488237
• Other study ID #: MTX side effects and VitD
• Status: Not yet recruiting
• Start date: September 2020
• Est. completion date: December 2021

Study information

• Verified date: July 2020
• Source: Assiut University
• Contact: Magy Ibrahim Anis Rizkallah, Bachelor
• Phone: 01282495775
• Email: magy_rezkallah[@]med.aun.edu.eg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 .

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 12 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Vitamin D
oral administration of Vitamin D in patients with acute leukemia treated with methotrexate

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (6)

Anand A, Singh S, Sonkar AA, Husain N, Singh KR, Singh S, Kushwaha JK. Expression of vitamin D receptor and vitamin D status in patients with oral neoplasms and effect of vitamin D supplementation on quality of life in advanced cancer treatment. Contemp Oncol (Pozn). 2017;21(2):145-151. doi: 10.5114/wo.2017.68623. Epub 2017 Jun 30. — View Citation

Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol. 2009 May 1;27(13):2151-6. doi: 10.1200/JCO.2008.19.6162. Epub 2009 Apr 6. — View 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. — View Citation

Hunger SP, Lu X, Devidas M, Camitta BM, Gaynon PS, Winick NJ, Reaman GH, Carroll WL. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children's oncology group. J Clin Oncol. 2012 May 10;30(14):1663-9. doi: 10.1200/JCO.2011.37.8018. Epub 2012 Mar 12. — View Citation

Lalla RV, Choquette LE, Feinn RS, Zawistowski H, Latortue MC, Kelly ET, Baccaglini L. Multivitamin therapy for recurrent aphthous stomatitis: a randomized, double-masked, placebo-controlled trial. J Am Dent Assoc. 2012 Apr;143(4):370-6. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of vitamin D administration on methotrexate adverse effects in patients with acute lymphoblastic leukemia	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.	1 to 2 years according to the availability of the cases