Diagnosis of Pheochromocytoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00004847
First received: March 2, 2000
Last updated: October 16, 2014
Last verified: March 2014
  Purpose

The goal of this study is to develop better methods of diagnosis and treatment for pheochromocytomas. These tumors, which usually arise from the adrenal glands, are often difficult to detect with current methods. Pheochromocytomas release chemicals called catecholamines, causing high blood pressure. Undetected, the tumors can lead to severe medical consequences, including stroke, heart attack and sudden death, in situations that would normally pose little or no risk, such as surgery, general anesthesia or childbirth.

Patients with pheochromocytoma may be eligible for this study. Candidates will be screened with a medical history and physical examination, electrocardiogram, and blood and urine tests. Study participants will undergo blood, urine, and imaging tests, described below, to detect pheochromocytoma. If a tumor is found, the patient will be offered surgery. If surgery is not feasible (for example, if there are multiple tumors that cannot be removed), evaluations will continue in follow-up visits. If the tumor cannot be found, the patient will be offered medical treatment and efforts to detect the tumor will continue. Diagnostic tests may include the following:

  1. Blood tests - Two blood tests glucagon stimulation and clonidine suppression are done that require insertion of intravenous (i.v.) catheters (thin flexible tubes) into arm veins. While the patient rests lying down, a drug (glucagon or clonidine) is given through the i.v. line. Blood pressure and heart rate are monitored frequently, and blood is collected from the i.v. line to measure levels of catecholamines and their breakdown products, metanephrines.
  2. Regional venous sampling - Selective vena caval sampling may be required for some patients. A catheter is placed into a large blood vessel called the inferior vena cava, through which blood circulating in the body returns to the heart. Blood samples are collected for measurement of catecholamines and metanephrines.
  3. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 131I-MIBG scanning. These scans may be done before and after surgical removal of pheochromocytoma.
  4. PET imaging - Positron emission tomography (PET) scanning is done using an injection of a radioactive catecholamine called fluorodopamine. The fluorodopamine enters pheochromocytoma cells, making the tumor radioactive and visible on the PET scan. The scan takes up to about 2 hours.
  5. Urine - A 24-hour urine collection is collected for analysis.
  6. Genetic testing A small blood sample is collected for DNA analysis.

PLEASE NOTE: Until further notice, we are not offering MIBG131 at this time.


Condition
Pheochromocytoma

Study Type: Observational
Official Title: Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To investigate the use of radiopharmaceutical tracer, F(18)-FLT for PET/CT scan in evaluating cellular proliferative behavior of various genetically inherited and sporadic pheochromocytomas and paragagliomas in adult patients.

Estimated Enrollment: 2000
Study Start Date: February 2000
Detailed Description:

Pheochromocytomas/paragangliomas are rare but clinically important chromaffin cell tumors that typically arise from the adrenal gland and constitute a surgically correctable cause of chronic hypertension. The clinical features and consequences of pheochromocytoma/paraganglioma result from the release of catecholamines (e.g., norepinephrine and epinephrine) by the tumor. If a pheochromocytoma/paraganglioma is undetected, stimuli that normally would not pose a hazard, such as surgery, childbirth, or general anesthesia, can evoke catecholamine secretion by the tumor, with clinically significant and even catastrophic outcomes. The diagnosis of pheochromocytoma/paraganglioma and its localization can be challenging, because measurements of plasma levels or urinary excretion of catecholamines and their metabolites and radio-iodinated metaiodobenzylguanidine (MIBG) scanning can yield false-negative results in patients harboring the tumor. Computed tomographic (CT) and magnetic resonance imaging (MRI) lack sufficient specificity. The molecular mechanisms by which genotypic changes predispose to development of pheochromocytoma/paraganglioma remain unknown, even in patients with identified mutations. Moreover, pheochromocytomas/paragangliomas in patients with hereditary predispositions differ in terms of their growth, malignant potential, catecholamine phenotype, and responses to standard screening tests such as glucagon stimulation and clonidine suppression tests. This protocol focuses on molecular and genetic studies that may elucidate the bases for predisposition to develop pheochromocytomas/paragangliomas and for expression of different neurochemical phenotypes and malignant potentials, new imaging approaches, based on [(18)F]-6F-dopamine ([(18)F]-6F-DA), and [(18)F]-L-3,4-dihydroxyphenylalanine ((18)F]-DOPA) positron emission tomographic (PET) scanning, [99m]Tc-methoxyisobutylisonitrile SPECT scintigraphy (99m Tc-MIBI), and new biochemical diagnostic criteria, based on measurement of plasma metanephrines. We also want to evaluate the benefits romidepsin pretreatment for uptake enhancement of [(123/131)I]-MIBG in pheochromocytoma/paraganglioma tumors.

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Patients are adults or children with known or suspected sporadic or familial pheochromocytoma/paraganglioma, on the basis of one or more of the following:

  • New onset of hypertension or hypertensive episodes and symptoms suggestive of pheochromocytoma/paraganglioma (sweating, headaches, pallor, palpitations).
  • High levels of blood or urinary catecholamines, metanephrines, or methoxytyramine.
  • Personal or family history of pheochromocytoma/paraganglioma or genetic mutations known to predispose individuals to develop pheochromocytoma/paraganglioma.

Signed informed consent is required.

Patients must be willing to return to NIH for follow-up evaluation.

Patients with pheochromocytoma/paraganglioma will be accepted through clinician or self referrals.

EXCLUSION CRITERIA:

Imaging studies are not done in pregnant or lactating women. A pregnancy test is performed in women of child-bearing age (up to age 55). In those with positive results, no PET scanning, MIBG scanning, contrast CT, DCE-MRI, vena cava sampling, glucagon and clonidine testing is performed.

Women who are pregnant are excluded from admission to the Clinical Center but may be studied as outpatients.

Imaging studies are not done in patients that have the following exclusion criteria:

  • Pregnant or lactating women,
  • Patients with impaired mental capacity that precludes informed consent,
  • Patients with a body weight of greater than or equal to 400 pounds due to weight limitations of the scanner or patients who are not able to enter the bore of the PET/CT scanner due to BMI,
  • Inability to lie still for the entire imaging time (e.g. cough, severe arthritis, etc.),
  • Inability to complete the needed investigational and standard-of-care imaging examinations due to other reasons (severe claustrophobia, radiation phobia, etc.),
  • Any additional medical condition, serious illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance.

Additionally DCE-MRI is not done in patients with acute or chronic renal insufficiency since gadolinium chelate injection is contraindicated in those patients. In patients where DCE-MRI is considered, a creatinine clearance measurement is performed as a clinically indicated test by the Department of Laboratory Medicine at the NIH Clinical Center. Patients with impaired kidney function will not undergo DCE-MRI. DCE-MRI is also not done in patients with severe claustrophobia or the presence of iron or metal in the MRI scan site, in patients with pacemakers or defibrillators, and in patients with an allergy to gadolinium.

Exclusion criteria for research PET imaging in children

Children of less than 10 years of age,

Children with impaired mental capacity that precludes informed assent,

Pregnant or lactating female adolescents,

Inability to lie still for the entire imaging time (e.g. cough, turbulent children, severe claustrophobia, etc.).

  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: NCT00004847

Contacts
Contact: Karen T Adams, C.R.N.P. (301) 402-7785 adamskt@mail.nih.gov
Contact: Karel Pacak, M.D. (301) 402-4594 karel@mail.nih.gov

Locations
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21205
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Netherlands
St. Radboud University Recruiting
Nijmegen, Netherlands
Sponsors and Collaborators
Investigators
Principal Investigator: Karel Pacak, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00004847     History of Changes
Other Study ID Numbers: 000093, 00-CH-0093
Study First Received: March 2, 2000
Last Updated: October 16, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Neurofibromatosis
Multiple Endocrine Neoplasia (MEN)
von Hippel-Lindau Disease
Norepinephrine
Epinephrine
Metanephrines
PET
Paraganglioma
Pheochromocytoma

Additional relevant MeSH terms:
Pheochromocytoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Paraganglioma

ClinicalTrials.gov processed this record on October 28, 2014