Epigenetic and Metabolomic Changes in Childhood Cancer Survivors

NCT03866707 | Terminated

• 2 other identifiers: IRB00048882CCCWFU 01118
• Study Type: observational
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Childhood Cancer

Outcome Measures

Primary Outcomes (2)

• 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

Interventions

One-time blood draw OTHER

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 OTHER

Evaluation of CpG methylation sites will be completed using the MethylationEPIC BeadChip (Infinium) microarray.

Metabolomic analysis OTHER

Metabolomic analysis will be performed by mass spectrometry when funds are available.

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• 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).

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Neoplasms

Study Officials

• Kevin Buckley, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2019
• First Posted: March 7, 2019
• Study Start: February 25, 2019
• Primary Completion: May 16, 2020
• Study Completion: May 16, 2020
• Last Updated: December 20, 2023

Record last verified: 2023-12

Locations

US (1)