NCT00004847

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. 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. 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. 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. 4.Genetic testing - A small blood sample is collected for DNA analysis and other analyses.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3,000

participants targeted

Target at P75+ for phase_1

Timeline
274mo left

Started Mar 2000

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress54%
Mar 2000Nov 2048

First Submitted

Initial submission to the registry

March 2, 2000

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 3, 2000

Completed
19 days until next milestone

Study Start

First participant enrolled

March 22, 2000

Completed
48.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2048

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2048

Last Updated

June 3, 2026

Status Verified

September 23, 2025

Enrollment Period

48.7 years

First QC Date

March 2, 2000

Last Update Submit

June 2, 2026

Conditions

PheochromocytomaEndocrine DiseaseEndocrine Diseases

Keywords

GeneticsMetanephrinesPETCatecholamines

Outcome Measures

Primary Outcomes (1)

  • To study specific genotypes, biochemical and imaging phenotypes of patients with various pheochromocytomas and paragangliomas.To stuty potential treatment options for metastatic pheochromocytoma and paraganglioma using cell cultures, cell ...

    To study specific genotypes, biochemical and imaging phenotypes of patients with various pheochromocytomas and paragangliomas.To stuty potential treatment options for metastatic pheochromocytoma and paraganglioma using cell cultures, cell lines, animal

    Baseline

Secondary Outcomes (1)

  • To educate health care professionals and patients about pheochromocytoma and paraganglioma

    end of study

Study Arms (1)

Adults or children with suspected PHEO/PGL

EXPERIMENTAL

Patients are adults or children of any age with known, sporadic or familial PHEO/PGL

Drug: ([18F]-DOPA)Drug: ([18F]-6F-DA)

Interventions

([18F]-DOPA)DRUG

is L 3, 4 dihydroxyphenylalanine (L-DOPA) labeled with the radioactive isotope 18F. In general, PPGLs belong to the group of neuroendocrine tumors. This heterogeneous group of tumors takes up amino acids, transforms them into biogenic amines (dopamine and serotonin) by decarboxylation and stores the amines in vesicles. L DOPA is a precursor of catecholamines (dopamine, norepinephrine and epinephrine). Epinephrine conversion to dopamine is catalyzed by the aromatic amino acid decarboxylase. According to previous and current studies, \[18F\]-DOPA PET is highly sensitive and specific for detection of PHEO/PGL67-69. However, there are only a few reports in the literature using \[18F\]-DOPA as a PET agent and particularly for patients with metastatic PPGLs. PET imaging will be done together with either a CT, an MRI or both modalities.

Adults or children with suspected PHEO/PGL
([18F]-6F-DA)DRUG

is an imaging agent developed at the NIH, that may improve specificity and sensitivity in the localization of PPGLs. \[18F\]-6F-DA enters cells via the membrane norepinephrine transporter. Once inside cells, \[18F\]-6F-DA is translocated via the vesicular monoamine transporter into storage vesicles, where the radioactivity is concentrated. After injection of \[18F\]-6F-DA, the much faster disappearance of \[18F\]-6F-DA-derived radioactivity from the bloodstream and non-neuronal cells than from chromaffin cells should enable rapid visualization of PPGLs by PET scanning.

Adults or children with suspected PHEO/PGL

Eligibility Criteria

Age3 Years - 120 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • High levels of blood or urinary catecholamines, metanephrines, methoxytyramine or chromogranin A.
  • Highly suspected presence of PHEO/PGL based on imaging studies, even with normal biochemistry.
  • Personal or family history of PHEO/PGL or genetic pathogenic variants known to predispose individuals to develop PHEO/PGL.
  • Signed informed consent is required. The informed consent may be signed by the patient, parent/guardian in pediatric patients or legally authorized representative (LAR) in adults who lack-decision making capacity to consent to research participation.
  • Patients must have an outside general practitioner or endocrinologist. Patients with metastatic disease must also have an outside oncologist.
  • Family Members of Patients Arm (Linkage Analysis)
  • Adult family members of patients enrolled in this study;
  • The index family member in this study has a suspected hereditary PHEO/PGL based on previous genetic testing and other suspicious hereditory patterns such as family history of multiple individuals with PHEO/PGL; early age of disease onset; multiplicity of primary tumors; recurrence, etc. and
  • Signed informed consent form is required

You may not qualify if:

  • Potential patients will be excluded on the basis of one or more of the following:
  • Pregnant or breastfeeding women
  • Severe cardiac dysfunction
  • Currently on dialysis
  • A pregnancy test is performed in women of childbearing age (up to age 55) as a screening after consenting. If a patient is found to have a positive pregnancy test, her participation in this protocol will be terminated. The patient can enroll or re-enroll in the protocol when she is no longer pregnant or breastfeeding.
  • In-person participating 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.
  • In adult patients (Excludes Linkage Analysis Arm)
  • 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 (e.g., 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.
  • In pediatric patients:
  • Children over 10 years old with very high suspicion of sporadic or familial PHEO/PGL based on at least one of the following:
  • The presence of new onset of symptoms typical of PHEO/PGL such as hypertension or hypertensive episodes, sweating, headaches, pallor, palpitations, drug resistant hypertension, etc.
  • Family history of PHEO/PGL or genetic pathogenic variants known to predispose individuals to develop these tumors.
  • The presence of a tumor on conventional imaging including ultrasound, CT and/or MRI or \[123I\]-MIBG or PET imaging not limited to \[18F\]-FDG.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (4)

  • Jha A, Patel M, Carrasquillo JA, Ling A, Millo C, Saboury B, Chen CC, Wakim P, Gonzales MK, Meuter L, Knue M, Talvacchio S, Herscovitch P, Rivero JD, Chen AP, Nilubol N, Taieb D, Lin FI, Civelek AC, Pacak K. Sporadic Primary Pheochromocytoma: A Prospective Intraindividual Comparison of Six Imaging Tests (CT, MRI, and PET/CT Using 68Ga-DOTATATE, FDG, 18F-FDOPA, and 18F-FDA). AJR Am J Roentgenol. 2022 Feb;218(2):342-350. doi: 10.2214/AJR.21.26071. Epub 2021 Aug 25.

    PMID: 34431366DERIVED

  • Wolf KI, Jha A, van Berkel A, Wild D, Janssen I, Millo CM, Janssen MJR, Gonzales MK, Timmers HJKM, Pacak K. Eruption of Metastatic Paraganglioma After Successful Therapy with 177Lu/90Y-DOTATOC and 177Lu-DOTATATE. Nucl Med Mol Imaging. 2019 Jun;53(3):223-230. doi: 10.1007/s13139-019-00579-w. Epub 2019 Feb 22.

    PMID: 31231443DERIVED

  • Abdul Sater Z, Jha A, Mandl A, Mangelen SK, Carrasquillo JA, Ling A, Gonzales MK, Lopes Abath Neto O, Miettinen M, Adams KT, Nockel P, El Lakis M, Pacak K. Gallbladder Paraganglioma Associated with SDHD Mutation: a Potential Pitfall on 18F-FDOPA PET Imaging. Nucl Med Mol Imaging. 2019 Apr;53(2):144-147. doi: 10.1007/s13139-018-0558-1. Epub 2019 Feb 19.

    PMID: 31057686DERIVED

  • Taieb D, Jha A, Guerin C, Pang Y, Adams KT, Chen CC, Romanet P, Roche P, Essamet W, Ling A, Quezado MM, Castinetti F, Sebag F, Pacak K. 18F-FDOPA PET/CT Imaging of MAX-Related Pheochromocytoma. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1574-1582. doi: 10.1210/jc.2017-02324.

    PMID: 29534198DERIVED

Related Links

MeSH Terms

Conditions

PheochromocytomaEndocrine System Diseases

Interventions

fluorodopa F 186-fluorodopamine

Condition Hierarchy (Ancestors)

ParagangliomaNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve Tissue

Study Officials

  • Catherine M Gordon, M.D.

    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Alberta Derkyi, C.R.N.P.

CONTACT

(301) 827-3355alberta.derkyi@nih.gov

Catherine M Gordon, M.D.

CONTACT

(301) 827-5449catherine.gordon@nih.gov

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 2, 2000

First Posted

March 3, 2000

Study Start

March 22, 2000

Primary Completion (Estimated)

November 30, 2048

Study Completion (Estimated)

November 30, 2048

Last Updated

June 3, 2026

Record last verified: 2025-09-23

Locations

US(1)