Epigenetic and Metabolomic Changes in Childhood Cancer Survivors

Childhood Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03866707
• Other study ID #: IRB00048882
• Secondary ID: CCCWFU 01118
• Status: Terminated
• Start date: February 25, 2019
• Est. completion date: May 16, 2020

Study information

• Verified date: December 2023
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: May 16, 2020
• Est. primary completion date: May 16, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Childhood Cancer

Intervention

Other:
• One-time blood draw
Subjects will have a one-time blood draw of 5-10mL. Quantity of blood drawn for study and routine care will not exceed the maximum safe blood volume for subject size. Evaluation of CpG methylation sites will be completed using the MethylationEPIC BeadChip (Infinium) microarray. This covers over 850,000 CpG methylation sites and is available in the investigator's Genomics Core Facility. Dr. Langefeld has analyzed numerous methylation studies, both array-based and next generation sequencing. Metabolomic analysis will be performed by mass spectrometry when funds are available.
• Evaluation of CpG methylation
Evaluation of CpG methylation sites will be completed using the MethylationEPIC BeadChip (Infinium) microarray.
• Metabolomic analysis
Metabolomic analysis will be performed by mass spectrometry when funds are available.

Locations

Country	Name	City	State
United States	Comprehensive Cancer Center of Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 ß value), and will be determined with GenomeStudio (Illumina, Inc.). For analysis, all ß 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
Primary	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