Epigenetic and Metabolomic Changes in Childhood Cancer Survivors

Epigenetic and Metabolomic Changes in Childhood Cancer Survivors as a Late Effect of Treatment - a Pilot Study

The purpose of this research study is to try and identify markers in childhood cancer survivors to help predict if they will develop late effects from their cancer treatment.

Study Overview

• Status: Terminated
• Conditions: Childhood Cancer
• Intervention / Treatment: Other: One-time blood draw; Other: Evaluation of CpG methylation; Other: Metabolomic analysis

Detailed Description

This is a pilot study to obtain preliminary data that will be used to apply for a larger grant to fund the full study with an adequate sample size for analysis.

Specific Aim 1. What are the epigenetic differences between children treated for childhood cancers and healthy controls matched for age, sex, ethnicity, geographic region, and tanner stage.

Specific Aim 2. Compare the metabolomic differences between children treated for childhood cancers and healthy controls matched for age, sex, ethnicity, geographic region, and tanner stage.

• Study Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center of Wake Forest University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The investigators propose to evaluate 8 patients who have been treated for childhood cancer and are at least 6 months off therapy. Because methylation patterns are known to change in different populations, 8 control patients matched for age, sex, and tanner stage will also be evaluated. Because of their under representation in clinical research, initially the investigators will recruit cancer survivors and controls of Caucasian Hispanic ethnicity from the same geographic region (i.e., Piedmont region of North Carolina).

Description

Inclusion Criteria:

• Childhood cancer survivors age 1-18 years old who received intensive treatment which included anthracycline and/or alkylating agent chemotherapy.
• Diseases which will be eligible include, high risk or very high risk acute lymphoblastic leukemia, acute myeloid leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, sarcomas.

Healthy controls:

• Healthy controls are defined as children ages 1-18 years old who are free from diseases or medical conditions that might be affected by or have an impact on this research study. Healthy controls will be matched with patients for age, sex, ethnicity, geographic region, and tanner stage, since it is known that these factors can affect the epigenetic signature of an individual. Controls will already be having blood drawn as part of their routine care.

Exclusion Criteria:

Cancer survivors:

• Patients who have received a bone marrow transplant will not be eligible.

Healthy controls:

• Age, sex, ethnicity, geographic region, and tanner stage matched controls with any acute or chronic disease will be excluded.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epigenetic Testing	Baseline and follow-up differences (predictor) in CpG methylation at sites on the EPIC array will be compared between subjects and controls (outcomes). Samples will be evaluated using the Infinium Methylation EPIC BeadChip microarray. This evaluates over 850,000 CpG methylation sites. The proportion of methylation for each site is based on the ratio of the fluorescence intensity of the methylated versus the combined methylated and unmethylated probes (referred to as the β value), and will be determined with GenomeStudio (Illumina, Inc.). For analysis, all β values will be converted to M values, where M is the log2 ratio of the methylated probe intensity to the unmethylated probe intensity.	Over 9 months
Metabolomic testing	Metabolic profiling will be done on serum using ultrahigh-performance liquid-phase chromatography and gas-chromatography separation, coupled with tandem mass spectrometry (UHPLC/MS/MS2 and GC/MS, respectively) at Metabolon, Inc. (Durham, NC, USA) using established procedures and technology. (10) samples will be collected at three time points based on disease type and will be flash frozen in liquid nitrogen after collection and stored at -80°C to ensure sample stability.	Over 9 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Kevin Buckley, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): May 16, 2020
• Study Completion (Actual): May 16, 2020

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 4, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: IRB00048882; CCCWFU 01118 (Other Identifier: Wake Forest University Health Science)

Drug and device information, study documents

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