Study of the Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01143519
First received: June 11, 2010
Last updated: March 14, 2014
Last verified: January 2014
  Purpose

Background:

- Research has shown that certain proteins in cells may be linked to higher risks of developing inflammations, tumors, and other medical problems. By examining how the blood cells of healthy volunteers respond to environmental exposures, researchers hope to better understand the relationship of genes, environmental factors, and human diseases.

Objectives:

- To examine how specific genes and proteins in blood cells respond to environmental exposures.

Eligibility:

- Healthy volunteers between 18 and 45 years of age.

Design:

  • The study will involve one visit of 45 to 60 minutes.
  • Participants will be screened with a brief physical examination and finger stick to determine if they are eligible to donate blood for the study, and will complete a questionnaire about any medications or other drugs (e.g., cigarettes) they may be taking.
  • Participants will provide a blood sample for research purposes.

Condition
Inflammation
Cancer
Cardiomyopathy

Study Type: Observational
Official Title: Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 420
Study Start Date: May 2010
Detailed Description:

This research study will investigate the role of SNPs in p53 and p53 response elements on the inflammatory response to DNA damage. A total of 210 healthy participants aged 18 years and older carrying one of the seven SNPs of interest and wild-type controls will be identified and recruited from the Environmental Polymorphism Registry (EPR). The EPR is a long-term project to collect and store up to 15,000 DNA samples for use in research studies from individuals in the greater North Carolina Triangle Region.

This observational gene association study will recruit participants on the basis of genotype and then observe the phenotype of each participant. The SNPs of interest are p53, as well as four of its downstream target genes including FLT1, MDM2, TLR8 and RRM1. A maximum of 150 mLs of blood will be obtained from each participant during one visit lasting approximately one hour. Cells from the donated blood samples will be examined for their response to exposed environmental stress ex vivo.

The primary objective is to determine the association between seven SNPs and p53 target gene expression after exposure to Nutlin or doxorubicin (chemotherapeutic agents) with outcome measured by RT-PCR. The seven SNPs are p53 rs1042522, p53 rs1800371, MDM2 rs2279744, MDM2 rs769412, FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952. The secondary objectives are to: (1) to determine the p53 promoter occupancy measured by ChIP analysis for the following SNPs: FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952; (2) to measure apoptosis by Annexin V-PI assay for SNPs p53 rs1042522 and p53 rs1800371; (3) to examine the cell cycle profile analysis (FACS) by cytofluorometry for SNPs p53 rs1042522 and p53 rs1800371; and (4) to determine DNA repair using Pulse Field Electrophoresis Gel (TAFE gels) for the following SNPs p53 rs1042522 and p53 rs1800371.

We hope the results of this study lead to discovery of important information regarding the role of SNPs located in p53 and p53 response elements in human disease, potentially identifying new targets for future studies.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:
  • Male or female 18 years of age or older
  • Participants must be able to understand and provide written informed consent to participate in the study
  • Participants must be able to travel to the CRU
  • Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. If the individual has a chronic condition such as diabetes or high blood pressure, healthy also means that they are being treated and the condition is under control).

EXCLUSION CRITERIA:

  • Use of immunosuppressants or other immune-modifying drugs [e.g., Rituxan, Humira, Enbrel, Cyclosporin (Neoral, Sandimmune, and SangCya), Azathioprine (Imuran)], Monoclonal antibodies [e.g., infliximab (Remicade)], Corticosteroids (e.g., prednisone, prednisolone and dexamethasone)
  • History of being treated for cancer by chemotherapy or radiation
  • Confirmed or suspected immunosuppressive or immunodeficient condition
  • Body weight < 50 kg (< 110 lbs)
  • Temperature > 37.6 C; blood pressure < 90/50 mm Hg or blood pressure > 170/95 mm Hg; pulse rate < 50 or > 100 beats/minute
  • Participants carrying SNPs TLR8 and FLT1 who are currently taking hormonal contraception (e.g. oral contraceptives, IUDs with hormones, contraceptive patches) or hormone replacement therapy will be excluded from the study unless the participant has been off of the hormone treatment for 1 month or longer.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01143519

Contacts
Contact: Lisa B Murphy (919) 541-9839 murphylb@mail.nih.gov
Contact: Michael A Resnick, Ph.D. (919) 541-4480 resnick@niehs.nih.gov

Locations
United States, North Carolina
NIEHS Clinical Research Unit (CRU) Recruiting
Research Triangle Park, North Carolina, United States
Contact: Lisa Murphy    919-541-9839    murphylb@mail.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Michael A Resnick, Ph.D. National Institute of Environmental Health Sciences (NIEHS)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT01143519     History of Changes
Other Study ID Numbers: 100134, 10-E-0134
Study First Received: June 11, 2010
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
p53
Inflammatory Response
Gene Association
Nutlin
Doxorubicin
Healthy Volunteer
HV

Additional relevant MeSH terms:
Cardiomyopathies
Inflammation
Cardiovascular Diseases
Heart Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 29, 2014