Effect of Omega-3 Fatty Acids on Methotrexate Induced Hepatotoxicity in Children With Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

Effect of Omega-3 Fatty Acids on Methotrexate Induced Hepatotoxicity in Children With Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02373579
• Other study ID #: Ain Shams University 1351
• Status: Completed
• Phase: Phase 2
• First received: February 2, 2015
• Last updated: February 23, 2015
• Start date: June 2012
• Est. completion date: October 2014

Study information

• Verified date: February 2015
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Higher Education
• Study type: Interventional

Clinical Trial Summary

Study the role of oxidative stress in methotrexate induced hepatic damage, and the possible protective effect of OMEGA-3 fatty acids against methotrexate hepatotoxicity using clinical and biochemical parameters.

Description:

The patients were divided into two groups :Group I: control group, included pediatric patients with standard risk acute lymphoblastic leukemia in maintenance phase day 0 and receiving oral Methotrexate (20 mg / m2) weekly without any supplementation .

Group II: study group, included standard risk ALL pediatric patients who were supplemented with oral omega-3 capsule (one capsule / day) .

Omega-3 was supplied as soft gelatin capsules in a dose of 1000 mg of omega-3 fatty acids/day . This is in addition to chemotherapy from day one of maintenance phase receiving oral Methotrexate (20 mg / m2) Weight -adjusted doses on days 8, 15, 22, 29,36,43,50,57,64,71and 78).

Both groups were followed up for six months . All patients were under free diet and were maintained on standard diet throughout the study ( 6 months). None of them were on regular vitamin supplementation before diagnosis or at time of chemotherapy administration.

Patients follow up:

The patients were followed up every three week for the whole study period for assessing the effect and compliance to both MTX and Omega-3 fatty acid and for monitoring any potential adverse effect.

Group I were asked on each visit about signs of hepatic toxicity ( fatigue , weakness , loss of appetite , vague abdominal pain , color of urine and sclera and jaundice ), their laboratory results were revised to know level of ALT as a marker of liver injury .

Group II were asked on each visit about signs of hepatotoxicity , their laboratory data were revised , any side effects resulted from use Omega-3 fatty acids:

(increased bleeding tendency, fishy smell , nausea , diarrhea , or if there is any relapses occurred , and to be sure that the patients were compliant to prescribed medication.

Investigations:

Blood samples were collected from every patient at day 0 of maintenance and after six months for estimation of Malondialdehyde (MDA), Total antioxidant capacity (TAC), super oxide dismutase ,liver function tests and uric acids . Blood was collected into heparinised tubes which were protected from light and processed immediately after sampling. At the time of collecting the blood samples, patients were free of any potentially confounding or interfering conditions, such as infections or fever.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 16 Years

Eligibility

Inclusion Criteria:

• Child age: less than 17 years old.

• Taking oral methotrexate in maintenance therapy.

• Patients are at cycle one day zero.

Exclusion Criteria:

• Child infected by hepatitis B or C viruses.

• Child taking medications or having a condition causing elevation in liver enzymes level other than methotrexate.(eg:thrombosis ,antibiotic therapy, infiltrating malignancy ,auto immune manifestations or having TPN)

• Child remission.

• Child death

• Child drop out due to non compliance

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

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

Intervention

Drug:
• Omega-3 Fatty Acids
study group, included standard risk ALL pediatric patients who were supplemented with oral omega-3 capsule (one capsule / day) . Omega-3 was supplied as soft gelatin capsules in a dose of 1000 mg of omega-3 fatty acids/day .
• Methotrexate
control group, included pediatric patients with standard risk acute lymphoblastic leukemia in maintenance phase day 0 and receiving oral Methotrexate (20 mg / m2) weekly without any supplementation .

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Nancy Samir Elbarbary

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability by measuring Malondialdehyde (MDA) level changes .		six months	Yes
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability by measuring Total antioxidant capacity (TAC) level changes.		six months	Yes
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability by measuring superoxide dismutase (SOD) level changes.		six months	Yes
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability by measuring uric acids levels changes .		Six months	Yes
Secondary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability by measuring ALT value changes.		six months	Yes