Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Diagnosis of Pheochromocytoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier:
NCT00004847
First received: March 2, 2000
Last updated: November 22, 2016
Last verified: November 2016

March 2, 2000
November 22, 2016
February 2000
Not Provided
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.
Not Provided
Complete list of historical versions of study NCT00004847 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Diagnosis of Pheochromocytoma
Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma

The goal of this study is to develop better methods of diagnosis, localization, 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. Main diagnostic and research tests may include the following:

  1. Blood tests - mainly measurements of plasma or urine catecholamines and metanephrines as well as methoxytyramine. If necessary the clonidine suppression test can be carried out.
  2. Standard imaging tests - Non-investigational imaging tests include computed tomography (CT), magnetic resonance imaging (MRI), sonography, and 123I-MIBG scintigraphy and FDG (positron emission tomography) PET/CT. These scans may be done before and/or after surgical removal of pheochromocytoma.
  3. Research PET scanning is done using an injection of radioactive compounds. Patients may undergo 18F-FDOPA, 18F-DA, as well as 68Ga-DOTATATE PET/CT . Each scan takes up to about 2 hours.
  4. Genetic testing - A small blood sample is collected for DNA analysis and other analyses.
Pheochromocytomas and paragangliomas are rare but clinically important chromaffin cell tumors that typically arise from the adrenal gland or from extra-adrenal paraganglia, respectively 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 as well as radio-iodinated metaiodobenzylguanidine (MIBG) scanning can yield false-positive/negative results in patients harboring the tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) lack sufficient specificity. The molecular mechanisms by which genotypic changes predispose to the 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, responses to standard screening tests, such as the clonidine suppression test, various imaging modalities, and different therapeutic options. This protocol focuses on developmental, molecular, genetic, epigenetic, proteomic, metabolomics, and other types of studies to elucidate the bases for predisposition to develop pheochromocytomas/paragangliomas and for expression of different neurochemical phenotypes and malignant potentials including therapeutic responses. Furthermore, this protocol will also use new imaging approaches, for example [(18)F]-6F-dopamine ([(18)F]-6F-DA), [(18)F]-L-3,4-dihydroxyphenylalanine ([(18F)]-DOPA), and [(68)Ga]-DOTA-Tyr-octreotate ([(68)Ga]-DOTATATE) positron emission tomography (PET)/CT, as well as PET/MRI scanning, and dynamic contrast-enhanced MRI. Additionally, new biochemical diagnostic criteria exist for the measurement of plasma metanephrines and methoxytyramine for the clinical diagnosis and localization of these tumors. This protocol will also evaluate the benefits of histone deacetylase inhibitors (e.g. romidepsin) pretreatment for uptake enhancement of [(123/131)I]-MIBG in pheochromocytoma/paraganglioma tumors.
Observational
Not Provided
Not Provided
Not Provided
Not Provided
Not Provided
Pheochromocytoma
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
2400
Not Provided
Not Provided
  • INCLUSION CRITERIA:
  • Patients are adults or children of any age with known or suspected sporadic or familial pheochromocytoma/paraganglioma, on the basis of one or more of the following:

    1. New onset of hypertension or hypertensive episodes and/or symptoms suggestive of pheochromocytoma/paraganglioma (e.g. but not only limited to, sweating, headaches, pallor, palpitations, drug-resistant hypertension).
    2. High levels of blood or urinary catecholamines, metanephrines, methoxytyramine, or chromogranin A.
    3. Highly suspected presence of pheochromocytoma or paraganglioma based on imaging studies, even with normal biochemistry.
    4. Personal or family history of pheochromocytoma/paraganglioma or genetic mutations known to predispose individuals to develop pheochromocytoma/paraganglioma.
  • Normal volunteers over the age of 18 years old, including those with normal or high blood pressure, are to be used for reference values regarding biochemical and imaging diagnosis of pheochromocytoma and paraganglioma.
  • Patients and normal volunteers can be studied to provide blood/urine samples for biochemical, proteomic, and/or genetic and epigenetic analysis.
  • Signed informed consent is required.
  • Patients must be willing to return to NIH for follow-up evaluation.
  • Patients must have an outside general practitioner or endocrinologist. Patients with metastatic disease must also have an outside oncologist.
  • Patients with pheochromocytoma/paraganglioma will be accepted through clinician or self- referrals.

EXCLUSION CRITERIA:

Potential patients will be excluded on the basis of one or more of the following;

  1. Pregnant or breastfeeding women
  2. Severe cardiac dysfunction
  3. Currently on dialysis

    If a previously enrolled female becomes pregnant, no imaging studies or biochemical workup will be performed until after delivery or the conclusion of breastfeeding. A pregnancy test is performed in women of childbearing age (up to age 55). In those with a positive pregnancy test, no PET and MIBG scanning contrast CT, DCE-MRI vena cava sampling or the clonidine test are performed.

    -Patients who are not willing to return to the NIH (e.g. after surgery or an initial evaluation) for more than 2 years may be removed from the protocol.

    SPECIFIC ELIGIBILITY CRITERIA FOR IMAGING STUDIES WITHIN OUR PROTOCOL:

    -In adult patients:

    --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 (Bullet)400 pounds due to weight limitations of PET/CT/MRI scanners or patients who are not able to enter the bore of PET/CT/MRI scanners 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 conditions, serious illness, or other extenuating circumstance that, in the opinion of the Principal 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 who have iron or metal in the MRI scan site, in patients with pacemakers or defibrillators, or in patients with an allergy to gadolinium.

    -In pediatric patients:

    • Inclusion criteria for research PET imaging in children

      ---Children over 10 years old with very high suspicion of sporadic or familial pheochromocytoma/paraganglioma (e.g. the presence of new onset of hypertension or hypertensive episodes, sweating, headaches, pallor, palpitations, drug resistant hypertension, etc.) family history of pheochromocytoma/paraganglioma or genetic mutations known to predispose individuals to develop these tumors, or the presence of a tumor on conventional imaging /ultrasounds, CT, MRI.

      ---Children must give written informed assent and be willing to return to the NIH for follow-up.

      • Female patients of childbearing age must have a negative pregnancy test within 24 hours of any treatment or test involving radioactivity or radiation exposure. They should be abstinent or use appropriate contraception while in the part of the study, which involves radiation.
    • 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.).
Both
7 Years and older   (Child, Adult, Senior)
Yes
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
United States
Netherlands
 
NCT00004847
000093, 00-CH-0093
Not Provided
Not Provided
Not Provided
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Principal Investigator: Karel Pacak, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health Clinical Center (CC)
November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP