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Trial record 47 of 47 for:    DOTATATE | Neuroendocrine Tumors

Diagnosis of Pheochromocytoma

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ClinicalTrials.gov Identifier: NCT00004847
Recruitment Status : Recruiting
First Posted : March 3, 2000
Last Update Posted : June 19, 2019
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) )

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Pheochromocytoma Endocrine Disease Endocrine Diseases Drug: Fluorodopamine Drug: F-18 Fluorodopa Phase 1

Detailed Description:
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare and clinically important chromaffin cell tumors that typically arise from the adrenal gland or from extra-adrenal paraganglia, respectively. The clinical features and consequences of PHEO/PGL result from the release of catecholamines (norepinephrine and epinephrine). An undetected PHEO/PGL poses a hazard to patients undergoing surgery, childbirth, or general anesthesia, due to the potential for excess catecholamine secretion, which can result in significant, often catastrophic outcomes. Diagnosing and localizing a PHEO/PGL can be challenging. Plasma and urinary catecholamines as well as their metabolites and 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 PHEO/PGL remain unknown even in patients with identified mutations. Moreover, in patients with hereditary predispositions, PHEOs/PGLs differ in terms of their growth, malignant potential, catecholamine phenotype, responses to standard screening tests, various imaging modalities and therefore subsequently, different therapeutic options. This protocol focuses on developmental, molecular, genetic, epigenetic, proteomic, metabolomics, immunologic and other types of studies to investigate the bases for predisposition to develop PHEOs/PGLs and for expression of different neurochemical and other phenotypes and malignant potentials including therapeutic responses. Furthermore, this protocol will also use new imaging approaches, for example [18F]-6F-dopamine ([18F]-6F-DA), [18F]-L-3,4-dihydroxyphenylalanine ([18F]-DOPA), and [68Ga]-DOTA-Tyroctreotate ([68Ga]-DOTATATE) positron emission tomography (PET)/CT, as well as PET/MRI scanning and dynamic contrast-enhanced MRI. Finally, this protocol aims to evaluate if pretreatment with histone deacetylase inhibitors (e.g., romidepsin) yields enhanced uptake of [123/131I]-MIBG in PHEOs/PGLs.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2400 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Diagnosis, Pathophysiology, and Molecular Biology of Pheochromocytoma and Paraganglioma
Study Start Date : March 1, 2000
Estimated Primary Completion Date : November 30, 2048
Estimated Study Completion Date : November 30, 2048


Arm Intervention/treatment
Experimental: 1
Patients or their relatives will have the disease and/or will be prescreened for genetic testing to identify genes
Drug: Fluorodopamine
Drug: F-18 Fluorodopa



Primary Outcome Measures :
  1. To study specific genotypes, biochemical and imaging phenotypes of patients with various pheochromocytomas and paragangliomas. Tostuty potential treatment options for metastatic pheochromocytoma and paraganglioma using cell cultures, cell lin... [ Time Frame: Baseline ]
    To study specific genotypes, biochemical and imaging phenotypes of patients with various pheochromocytomas and paragangliomas. Tostuty potential treatment options for metastatic pheochromocytoma and paraganglioma using cell cultures, cell lines, animal


Secondary Outcome Measures :
  1. To educate health care professionals and patients about pheochromocytoma and paraganglioma
    To educate health care professionals and patients about pheochromocytoma and paraganglioma



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 150 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients are adults or children of any age with known, sporadic or familial PHEO/PGL, on the basis of one or more of the following:

    1. High levels of blood or urinary catecholamines, metanephrines, methoxytyramine or chromogranin A.
    2. Highly suspected presence of PHEO/PGL based on imaging studies, even with normal biochemistry.
    3. Personal or family history of PHEO/PGL or genetic mutations known to predispose individuals to develop PHEO/PGL.
  • Normal volunteers over the age of 18 years, including those with normal or high blood pressure, are to be used for reference values regarding biochemical and imaging diagnosis of PHEO/PGL. Normal volunteers with high blood pressure can be on blood pressure medication.
  • 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 PHEO/PGL 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 (based on a pregnancy test done either outside the NIH or at the NIH) or breastfeeding women
  2. Severe cardiac dysfunction
  3. Currently on dialysis

    -A pregnancy test is performed in women of childbearing age (up to age 55). If after enrollment to this protocol, a patient is found to have a positive pregnancy test, her participation in this protocol will be terminated.

    -Research scans are contraindicated in patients with proven myelodysplastic syndrome.

    • 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.
    • If the patient is eligible for a surgery and chooses to receive a surgical intervention at a place outside of the NIH, his/her decision may affect future participation in the study. We also understand that due to extenuating circumstances the patient may need to pursue the surgery somewhere else. Under those circumstances, our team will provide a list of necessary criteria for continued follow-up (i.e. tissue transfer, follow-up tests, etc.).

      --The patient will need to inform the research team ahead of time about the surgeon and institution that will be performing the surgery, so that the team can aid in facilitating the appropriate arrangements for tissue transfer.

      --The patient will need to consult with the outside surgeon to develop a plan for sending a sample of tumor tissue to the NIH research team. If the surgeon is not consulted or the sample is not transferred, we may inform participants that their enrollment in the study may no longer be scientifically appropriately. In this case, the research team will work with the participant to develop a plan to obtain medical records to facilitate transfer of care in patient s preferred facility.

    • Pregnant and breastfeeding women will not be included in the protocol because their participation as a demographic is not essential to this study. The information we are seeking can be acquired from a cohort of non-pregnant patients. The exclusion of pregnant women does not preclude these patients from receiving appropriate care and management from an outside facility.

    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 and breastfeeding women,
      • Patients with a body weight of greater than or equal to 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. Very rarely, gadolinium at the site of injection or the dosed limb can cause skin and soft tissue necrosis, thrombosis, fasciitis, and compartment syndrome requiring surgical intervention.

    -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 on the day of the enrollment into this protocol and within 24 hours of any treatment or test involving radioactivity or radiation exposure. They should be abstinent or use appropriate contraception while taking part in 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 breastfeeding female adolescents,
    • Inability to lie still for the entire imaging time (e.g. cough, turbulent children, severe claustrophobia, etc.).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00004847


Contacts
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Contact: Marianne M Knue, C.R.N.P. (301) 827-3355 marianne.knue@nih.gov
Contact: Karel Pacak, M.D. (301) 402-4594 karel@mail.nih.gov

Locations
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United States, Maryland
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 Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
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Principal Investigator: Karel Pacak, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00004847     History of Changes
Other Study ID Numbers: 000093
00-CH-0093
First Posted: March 3, 2000    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: May 16, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
Genetics
Metanephrines
PET
Catecholamines
Pheochromocytoma

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