Protocol Number: 07-H-0030

Title:

Metabolic Regulation by Tumor Suppressor p53 in Li-Fraumeni Syndrome

Number:

07-H-0030

Summary:

This study will examine metabolic and biological factors in people with Li-Fraumeni syndrome, a rare hereditary disorder that greatly increases a person's susceptibility to cancer. Patients have a mutation in the p53 tumor suppressor gene, which normally helps control cell growth. This gene may control metabolism as well as cancer susceptibility, and the study findings may help improve our understanding of not only cancer but also other conditions, such as cardiovascular function.

Healthy normal volunteers and patients with the Li-Fraumeni syndrome and their family members may be eligible for this study. Candidates must be at least 18 years of age, in overall good health and cancer-free within 1 year of entering the study. Participants undergo the following procedures:

" Blood tests for routine lab values and for research purposes.

" ECG and echocardiogram (heart ultrasound) to evaluate heart structure and function.

" Resting and exercise metabolic stress testing: The subject first relaxes in a chair wearing the facemask and then exercises on a stationary bicycle or treadmill while wearing the mask. This test uses the facemask to measure oxygen usage by the body to determine metabolic fitness. Electrodes are placed on the body to monitor the heart in an identical manner to a standard exercise stress test.

" Magnetic resonance imaging of metabolism: The subject lies on a bed that slides into a large magnet (the MRI scanner) for up to 60 minutes. During scanning, the arm or leg muscles are stressed by inflating a blood pressure cuff and by exercising the limb for several minutes. Subjects may be asked to squeeze a rubber ball or exercise with a foot pedal. Immediately afterwards, the pressure in the cuff is released and remains deflated for 10 to 15 minutes. No more than three 5-minute episodes of blood flow stoppage are performed.

" Standard MRI scan of exercised limb to determine muscle volume.

" Brachial artery reactivity test to measure blood vessel function: Before the exercise stress testing, subjects lie on a stretcher while the brachial artery (artery in the forearm) is imaged using a noninvasive ultrasound method. Artery size and blood flow velocity are measured before and after inflating a blood pressure cuff on the forearm. Vessel size and flow velocity measurements are repeated after 15 minutes and again after administration of nitroglycerin under the tongue.

" Oral glucose tolerance testing to test for diabetes: To assess sugar metabolism, subjects drink a sugar solution. Blood samples are collected before drinking the solution and 1 and 2 hours after drinking the solution.

" Muscle biopsy (optional according to subject preference): Subjects may be given small amounts of sedation for the procedure. A small area of skin over a leg muscle is numbed and a small amount of muscle tissue is surgically removed.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1) At least 18 years of age and able to give informed consent

2) Cancer-free within the past one year prior to time of study enrollment

3) Be in overall good health

4) Able to exercise on a treadmill

EXCLUSION CRITERIA:

1) Cancer, radiation or chemotherapy within the past one year prior to time of study enrollment

2) Blood pressure higher than 160/90 mmHg

3) Diabetes requiring medical treatment

4) Anemia

5) Tobacco use within the past three months

6) History of ischemic heart disease, heart failure or peripheral vascular disease

7) Coagulopathy or any other disease predisposing to vasculitis or Raynaud's phenomenon

8) Treatment with bone marrow transplantation

9) Inflammatory disease or immunosuppressive therapy

10) Claustrophobia and/or unable to lie on your back in the MRI machine

11) Pregnant or breast feeding

12) Body mass index under 19 or over 35

13) Metal medical implantable device or other MRI incompatible materials

Special Instructions:

Currently Not Provided

Keywords:

Mitochondria

Ischemia

Oxygen Consumption

Aerobic Capacity

Magnetic Resonance Spectroscopy

Recruitment Keyword(s):

Li-Fraumeni Syndrome

Condition(s):

Li-Fraumeni Syndrome

Cardiovascular Capacity

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Heart, Lung and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Arena R, Myers J, Abella J, Peberdy MA. Influence of heart failure etiology on the prognostic value of peak oxygen consumption and minute ventilation/carbon dioxide production slope. Chest. 2005 Oct;128(4):2812-7.

Brown BW, Costello TJ, Hwang SJ, Strong LC. Generation or birth cohort effect on cancer risk in Li-Fraumeni syndrome. Hum Genet. 2005 Dec;118(3-4):489-98. Epub 2005 Nov 12.

Combs CA, Aletras AH, Balaban RS. Effect of muscle action and metabolic strain on oxidative metabolic responses in human skeletal muscle. J Appl Physiol. 1999 Nov;87(5):1768-75.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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