We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Specificity of Elevated Plasma EM66 Levels in Pheochromocytoma (PHEO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01022515
Recruitment Status : Completed
First Posted : December 1, 2009
Last Update Posted : June 19, 2014
Information provided by (Responsible Party):

Study Description
Brief Summary:
Pheochromocytoma or paraganglioma are tumors generating hypertension as a symptom. Different biological tests are currently available to diagnose these tumors. However, they all lack specificity since they do not distinguish cases of hypertension without pheochromocytoma or paraganglioma. To improve the diagnostic specificity of these tumors, the investigators are testing a new marker called EM66.

Condition or disease Intervention/treatment
Pheochromocytoma Paraganglioma Essential Hypertension Other: plasma EM66 & CgA levels assessment Other: usual follow up with regular EM66 & Cga levels assessment

Detailed Description:
Neuroendocrine tumors (NT) correspond to neoplasms that develop from endocrine and neuroendocrine cells scattered throughout the body. They are characterized by the occurrence, in their cytoplasm, of dense-core secretory vesicles containing hormones, neuropeptides and acidic proteins such as granins. The diversity of NT (from hypophysis, pancreas, adrenal, gastrointestinal tract) makes very difficult the identification and evaluation of the different types of tumors by the diagnostic and prognostic tools currently available. We have thus established a research program aimed at identifying new biological markers for the detection, the prognosis and the follow-up of NT by seeking in tumor and plasma samples of patients, granin-derived peptides. Our program was initiated on one type of NT : pheochromocytoma. These neoplasms correspond to tumoral chromaffin cells mainly originating from the adrenal medulla. It is considered that 10 % of pheochromocytoma patients will develop metastases and, currently, except in the presence of metastases, there are no means to predict malignancy of the tumor. We setup a radioimmunoassay of EM66 (a secretogranin II-derived peptide) that allowed us to demonstrate that (i) plasma concentrations of the peptide are significantly elevated in pheochromocytoma patients, (ii) combined with other biological tests EM66 measurement increase the diagnostic sensitivity for these neoplasms, (iii) after surgical removal of the tumor, plasma EM66 concentrations rapidly return to basal level and, (iv) intra-tumoral EM66 concentrations are higher in benign than in malignant pheochromocytomas (Yon et al., 2003, Guillemot et al., 2006). These results reveal that EM66 constitutes a novel tool for the diagnosis, prognosis and follow-up of pheochromocytoma. In the frame of a clinical use of an EM66 measurement test, it is necessary to evaluate the specificity of this marker. For instance, renal deficiency, hypergastrinemia, reduction of renal clearance, type A gastritis, Crohns disease, or proton-pump inhibitory treatment, lead to increase plasma chromogranin A (CgA) concentrations (false-positive cases). In addition, while hypertension account for one of the symptoms of pheochromocytoma patients, in essential hypertensive patients, CgA levels are higher than in normotensive individuals. The main objective of our clinical transfer research project consists to study the specificity of the measurement of EM66 as a diagnostic and prognostic marker of pheochromocytoma. This multicentric study will allow us to compare plasma EM66 levels in pheochromocytoma patients with a cohort of essential hypertensive patients. At the same time, in a long-range prospect, due to the lack of malignancy markers for these tumors, we will investigate if plasma or tumor EM66 levels are correlated to the differentiation status of pheochromocytomas, and if the expression level of a set of genes that we identified by a transcriptomic approach developed in the laboratory, is associated with the malignant status of the tumors. The stakes of this transfer research, involving our laboratory and the Center for Clinical Investigations (CIC) of Rouen and Lille, are to provide an easy and simple novel tool to practitioners and anatomo-pathologists for the screening, the evaluation and the follow-up of patients with neuroendocrine tumors.

Study Design

Study Type : Observational
Actual Enrollment : 60 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Clinical Application of New Pheochromocytoma Markers: INSERM Pilot Study of the Specificity of Elevated Plasma EM66 Concentrations in Patients With Pheochromocytoma or Paraganglioma Compared to Patients With Essential Hypertension
Study Start Date : November 2008
Primary Completion Date : December 2013
Study Completion Date : December 2013

Groups and Cohorts

Group/Cohort Intervention/treatment
patients with pheochromocytoma
Patients with pheochromocytoma / paraganglioma are being followed as recommended according to international standards. No intervention is expected except regular measurement of plasma CgA (as usual) and EM66 (research purpose) levels.
Other: usual follow up with regular EM66 & Cga levels assessment

Patients with pheochromocytoma / paraganglioma will be followed-up as the international standards recommend.

Regularly, blood samples will be drawn for the usual assessment of CgA levels and also EM66 (research purpose) levels.

Patients with essential hypertension
Patients with essential hypertension will be selected as controls. EM66 and CgA plasma levels will be assessed in these patients after having excluded the presence of a pheochromocytoma / paraganglioma with normal urinary metanephrines / normetanephrines excretion levels.
Other: plasma EM66 & CgA levels assessment
After inclusion checking to eliminate the presence of pheochromocytoma / paraganglioma, a blood sample will be drawn to assess plasma EM66 and CgA levels.

Outcome Measures

Primary Outcome Measures :
  1. Plasma EM66 [ Time Frame: two years ]

Secondary Outcome Measures :
  1. Plasma Chromogranin A levels [ Time Frame: before treatement ]

Biospecimen Retention:   Samples Without DNA
5 ml blood sample on EDTA to collect 2,5 ml plasma, kept at -80°C, once a year.

Eligibility Criteria

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.

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

two distint population will be involved :

  • patients with pheochromocytoma or paraganglioma
  • patients with essential hypertension

Patients with pheochromocytoma/paraganglioma

Inclusion criteria :

  • men & women, age > 18 years old
  • Newly diagnosed patient : suspicion of pheochromocytoma or paraganglioma with elevation of urinary metanephrines and/or normetanephrines along with evidence of tumor which surgical removal is considered (histological findings following surgery will be the gold standard for final diagnosis and inclusion in the study)
  • During follow-up of a patient with known genetic predisposition to pheochromocytoma/paraganglioma : suspicion of pheochromocytoma or paraganglioma with or without elevation of urinary metanephrines and/or normetanephrines along with evidence of a tumor which surgical removal is considered (histological findings following surgery will be the gold standard for final diagnosis and inclusion in the study) ,
  • Patients with known pheochromocytoma/paraganglioma, whether malignant or not, whether with metanephrine secretion or not, With tumor sites at inclusion in the study
  • Patients informed and willing to participate in the study
  • Patients with medical insurance (French social security) Non inclusion criteria
  • Patients newly diagnosed, recently operated and the histological findings disprove pheochromocytoma or paraganglioma.
  • patient imprisoned or under legal protection.

Patients with essential hypertension Inclusion criteria

  • men & women, age > 18 years old
  • paired with a patient with pheochromocytoma/paraganglioma for : gender, age (± 5 years) and centre
  • patient with hypertension. No aetiology was found after initial check up.
  • Normal 24 hours urinary excretion of metanephrines & normetanephrines
  • For women of childbearing potential : effective contraceptive method and negative urinary pregnancy test
  • Patients informed and willing to participate in the study
  • Patients with medical insurance (French social security) Non inclusion criteria
  • Treatment with proton-pump inhibitors in the 8 days before inclusion in the study
  • Treatment with beta-blockers, antidepressants, Benzodiazepins, dopa, alphamethyl dopa, if this treatment cannot be interrupted during the study (i.e. for approximately 10 days)
  • patient imprisoned or under legal protection.
Contacts and Locations

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): NCT01022515

CIC 9301
Lille, France, 59000
Endocrinology Department
Lille, France, 59000
Inserm U982/EA 4310; Rouen University (DC2N)
Mont Saint Aignan, France, 76800
Cardiology Department
Paris, France, 75012
CIC 9304
Paris, France, 75012
Cic-Crb 0204
Rouen, France, 76000
Endocrinology Department
Rouen, France, 76000
Endocrinology Department, Gustave-Roussy Institute
Villejuif, France, 94000
Sponsors and Collaborators
University Hospital, Rouen
Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator: Anne F Cailleux, MD Rouen University Hospital
More Information

Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT01022515     History of Changes
Other Study ID Numbers: 2007/081/HP
2007-AO1004-49 ( Registry Identifier: RCB )
First Posted: December 1, 2009    Key Record Dates
Last Update Posted: June 19, 2014
Last Verified: June 2014

Keywords provided by University Hospital, Rouen:

Additional relevant MeSH terms:
Carotid Body Tumor
Paraganglioma, Extra-Adrenal
Vascular Diseases
Cardiovascular Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue