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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

10-E-0134

Sponsoring Institute

National Institute of Environmental Health Sciences (NIEHS)

Recruitment Detail

Type: Enrolling by Invitation
Gender: Male & Female
Min Age: 18
Max Age: 100

Referral Letter Required

Yes

Population Exclusion(s)

Children;
Pregnant Women and Fetuses

Special Instructions

Currently Not Provided

Keywords

Gene Expression;
Apoptosis;
Lymphocytes;
Environmental Factors;
Single Nucleotide Polymorphism

Recruitment Keyword(s)

Healthy Volunteer;
HV

Condition(s)

HIV-1 Seropositive;
Inflammation;
Cancer;
Cardiomyopathy

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Environmental Health Sciences

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.

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Eligibility

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

-Nonpregnant

-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).

-Participants with health outcomes identified by genotype-phenotype association studies.

-HIV-1 seropositive under medicament treatment (for HIV P53 and TLR8 groups only) (checked every 6 months at visit)

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)] (for healthy controls only)

-Chronic use of systemic, inhaled steroids

-Current or use of prescription strength topical corticosteroids within the last 7days

-History of cancer, including skin cancer (for healthy controls only)

-History of chemotherapy or radiation treatment (for healthy controls only)

-Confirmed or suspected immunosuppressive or immunodeficient condition (for healthy controls only)

-Hepatitis B/C-positive status (checked every 6 months at visit)

-Body weight < 50 kg (<110 lbs)

-If blood donation exceeds 200ml:

--Hematocrit <34% for women or <36% for men, or >56% for either gender

-Temperature > 37.6 C; blood pressure < 90/50 mm Hg or blood pressure >160/100 mm Hg; pulse rate < 50 or > 100 beats/minute

-Blood or plasma donation that will cause the participant to exceed 550ml of blood in the last 8 weeks

-HIV1 donors with opportunistic infections:

--Candidiasis of bronchi, trachea, esophagus, or lungs

--Invasive cervical cancer

--Coccidioidomycosis

--Cryptococcosis

--Cryptosporidiosis, chronic intestinal (greater than 1 month's duration)

--Cytomegalovirus disease (particularly CMV retinitis)

--Encephalopathy, HIV-related

--Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis

--Histoplasmosis

--Isosporiasis, chronic intestinal (greater than 1 month's duration)

--Kaposi's sarcoma

--Lymphoma, multiple forms

--Mycobacterium avium complex

--Tuberculosis

--Pneumocystis carinii pneumonia

--Pneumonia, recurrent

--Progressive multifocal leukoencephalopathy

--Salmonella septicemia, recurrent

--Toxoplasmosis of brain

--Wasting syndrome due to HIV

* HIV and hepatitis results will be confidentially obtained. Testing will be contracted to an external certified laboratory. Results will be available only to the study team, with the few caveats that follow:

All positive HIV, hepatitis B, and hepatitis C results that are unexpected (i.e. participant is not currently enrolled in the EPR as an HIV-1 seropositive under medicament treatment) will be promptly communicated to the donor by the study doctor/PI or the CRU Director. The participant will be referred to their physician and/or to the N.C. Department of Health for confirmatory testing and counseling. As explained in detail in the attached Supplement describing N.C. State Department of Health code will be followed. The state code mandates reporting of positive results along with the participant s name and identifying information to the N.C. Department of Public Health. Upon contracting with the testing laboratory, clarification will be obtained and documented as to whether the contracted laboratory or the study MD will be responsible for reporting positive results to the state to avoid duplication of reporting. Upon receipt of the test results, the N.C. Department of Health will contact the participant to inform them of the positive result, how to find care, how to avoid infecting others, how the newly diagnosed HIV and/or hepatitis infection is reported, and the importance of informing their partners at possible risk because of their HIV and/or hepatitis infection. If the HIV, hepatitis B, and hepatitis C results are negative, the participant will be not be notified. However, the participant may contact the research study nurse for their results.

HIV and hepatitis B/C test results, non-reactive and reactive, will be documented confidentially by the PI or study coordinator in the subject s file, and kept in a locked file cabinet in the CRU Medical Records Room. In order to document the reporting procedure and the time associated with the reporting process, a document has been created and placed in the study specific manual (Hepatitis B/C and HIV Notification Process for Reactive Results Form).

-Healthy control 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.


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Citations:

Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G, Levine AJ. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004 Nov 24;119(5):591-602.

Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer. 2009 Oct;9(10):724-37.

Murphy ME. Polymorphic variants in the p53 pathway. Cell Death Differ. 2006 Jun;13(6):916-20.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Daniel Menendez, Ph.D.
National Institute of Environmental Health Sciences (NIEHS)
National Institute of Environmental Health Sciences
111 T.W. Alexander Drive (MD D3-01)
Research Triangle Park, NC 27709

(984) 287-4105
menendez@mail.nih.gov

Lisa B. Barber, MEd
National Institute of Environmental Health Sciences (NIEHS)
Building 109 - Modular Clinic, 121
111 T W Alexander Dr
Research Triangle Prk, NC, 27709
(984) 287-4410
lisa.barber@nih.gov

Lisa B. Barber, MEd
Building 109 - Modular Clinic, 121
111 T W Alexander Dr
Research Triangle Prk, NC, 27709
(984) 287-4410
lisa.barber@nih.gov

Clinical Trials Number:

NCT01143519

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