Effect of Fish Oil on Hyperlipidemia and Toxicities in Children and Young Adults With Acute Lymphoblastic Leukemia

Effect of Fish Oil Versus Placebo on Hyperlipidemia and Toxicities in Children and Young Adults With Acute Lymphoblastic Leukemia - A Randomized Controlled Trial

Acute lymphoblastic leukemia (ALL) is the most common malignant disease among children. Treatment results have improved over time due to intensive risk-adapted therapy and the 5-year survival rate is now above 90%. However, the burden of therapy has increased proportionally. Many children develop serious acute and chronic side effects, which impact on the patients expected lifespan and impair their quality of life as a result of therapy. Treatment with PEG-asparaginase and dexamethasone increases the levels of triglycerides and total cholesterol. Consequently, the incidence of hyperlipidemia is high during initial ALL therapy. Studies have suggested that hyperlipidemia is a risk factor for development of osteonecrosis, thrombosis and possibly acute pancreatitis.

Long-chained marine omega-3 fatty acids, found in fish oil, decrease levels of triglycerides and total cholesterol in hyperlipidemic patients. Due to the high survival rate, it is of great interest to develop methods to reduce treatment related toxicities.

The investigators hypothesise that daily intake of fish oil will prevent development of hyperlipidemia during ALL treatment phases with dexamethasone and PEG-asparaginase compared to placebo and that fish oil intake may reduce the incidence of severe adverse events related to ALL treatment.

Study Overview

• Status: Recruiting
• Conditions: Leukemia, Acute Lymphoblastic
• Intervention / Treatment: Dietary supplement: Eskimo-3 Pure Fish Oil; Dietary supplement: Rapeseed Oil

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Renate Dagsdottir Laumann, MSc; Phone Number: +4560163957; Email: renate.dagsdottir.laumann@regionh.dk

Study Locations

• Denmark
  • Aalborg, Denmark
    • Not yet recruiting
    • Aalborg University Hospital
    • Contact: Steen Rosthøj, MD
  • Aarhus, Denmark
    • Not yet recruiting
    • Aarhus University Hospital
    • Contact: Birgitte Klug Albertsen, MD
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Renate Dagsdottir Laumann, MSc; Phone Number: +4560163957; Email: renate.dagsdottir.laumann@regionh.dk
  • Odense, Denmark
    • Not yet recruiting
    • Odense University Hospital
    • Contact: Peder Skov Wehner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children (1-17.9 years) and young adults (18-45 years) diagnosed with ALL, stratified to very-low risk (VRL), intermediate risk low (IR-low) and intermediate risk high (IR-high) in the ALLTogether protocol.

Exclusion Criteria:

• Patients diagnosed with ALL, stratified to high risk (HR) after induction treatment or stem cell transplantation in the ALLTogether protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fish oil; Eskimo-3 Pure Fish Oil, 10 ml per day (2.6 g EPA+DHA)	Dietary supplement: Eskimo-3 Pure Fish Oil; Dosage: 10 ml/day (2.6 g EPA+DHA); Other Names: Fish Oil
Placebo Comparator: Placebo; Rapeseed Oil, 10 ml per day	Dietary supplement: Rapeseed Oil; Dosage: 10 ml/day (0 g EPA+DHA); Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyperlipidemia	Triglycerides and/or total cholesterol levels five times or more than the age-dependent upper normal limit.	From treatment day 4 until treatment day 169 or 204

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid metabolism	Triglycerides, total cholesterol, VLDL-cholesterol, LDL-cholesterol and HDL-cholesterol.	VLR and IR-low: 4, 11, 18, 25, 32, 39, 46, 53, 60, 67, 81, 95, 109, 123, 137, 151 and 169. IR-high: treatment day 4, 11, 18, 25, 32, 39, 46, 53, 60, 67, 74, 81, 88, 95, 102, 109, 123, 137, 151, 165, 179, 193 and 204.
Compliance	Assessed by self-registration forms, return of bottles and levels of EPA+DHA in whole blood	From treatment day 4 until end of intervention (treatment day 169 or 204)
Bone density	Assessed by DEXA-scan and bone biomarkers (iCa, PTH, vit D, phosphate, magnesium, creatinine, alkaline phosphatase, CTX, P1NP.	DEXA-scan at start and end of intervention. Bone biomarkers at treatment day 4, 81 and 169 for VLR and treatment day 4, 102 and 204 for IR-low and IR-high.
Hemostatic status	Thromboelastography (TEG), multiplate and thrombocytes.	At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high
Endothelial function	sTM, syndecan-1, PECAM, VEGFR1	At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high
Incidence of severe adverse events	Cumulative incidence of osteonecrosis, asparaginase associated pancreatitis and thrombosis.	From treatment day 4 until end of intervention (treatment day 169 or 204)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Milder side effects	Assessed by questionnaire.	At end of intervention (day 169 or 204)
Dietary intake	Assessed by 3-day food records	At treatment day 4, 81 and 169 for VLR and at treatment day 4, 102 and 204 for IR-low and IR-high

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Danish Child Cancer Foundation
• Investigators: Study Chair: Thomas Leth Frandsen, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2019
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: December 19, 2019
• First Submitted That Met QC Criteria: December 19, 2019
• First Posted (Actual): December 24, 2019

Study Record Updates

• Last Update Posted (Actual): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 23, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lipid Metabolism Disorders; Dyslipidemias; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Hyperlipidemias; Hyperlipoproteinemias
• Other Study ID Numbers: H-19054660

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No