PheochromocytomaPHEONCT01022515
Specificity of Elevated Plasma EM66 Levels in Pheochromocytoma
A study testing plasma EM66 & CgA levels assessment and usual follow up with regular EM66 & Cga levels assessment in people with Pheochromocytoma and Paraganglioma, run by University Hospital, Rouen at 8 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Pheochromocytoma, Paraganglioma, Essential Hypertension
- What is being tested?
- plasma EM66 & CgA levels assessment and usual follow up with regular EM66 & Cga levels assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 8 sitesFrance
- Study dates
- Nov 2008to 13 Apr 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 19Show fewer
- 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.
Who cannot join
None listed.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
CIC 9301
Lille, 59000
Endocrinology Department
Lille, 59000
Inserm U982/EA 4310; Rouen University (DC2N)
Mont-Saint-Aignan, 76800
Cardiology Department
Paris, 75012
CIC 9304
Paris, 75012
Cic-Crb 0204
Rouen, 76000
Endocrinology Department
Rouen, 76000
Endocrinology Department, Gustave-Roussy Institute
Villejuif, 94000
About this study
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
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.
Read the 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.
- Conditions
- Pheochromocytoma, Paraganglioma, Essential Hypertension
- Being tested
- plasma EM66 & CgA levels assessment, usual follow up with regular EM66 & Cga levels assessment
- Keywords
- pheochromocytoma, paraganglioma, hypertension
- Medical subject headings
- Pheochromocytoma, Paraganglioma, Essential Hypertension, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
plasma EM66 & CgA levels assessmentOther
After inclusion checking to eliminate the presence of pheochromocytoma / paraganglioma, a blood sample will be drawn to assess plasma EM66 and CgA levels.
usual follow up with regular EM66 & Cga levels assessmentOther
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.
| Study group | Role | What they receive |
|---|---|---|
| patients with pheochromocytoma | Other | 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. Receives: Other: usual follow up with regular EM66 & Cga levels assessment |
| Patients with essential hypertension | Other | 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. Receives: Other: plasma EM66 & CgA levels assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma EM66
Measured: two years
Secondary outcomes (1)
Plasma Chromogranin A levels
Measured: before treatement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2009 (estimated)
- Study startNov 2008
- Primary completion13 Apr 2022
- Study completion13 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PheochromocytomaStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne F Cailleux, MD, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01022515
- Sponsor's protocol ID
- 2007/081/HP
- Other IDs
- 2007-AO1004-49
- Acronym
- PHEO
- Status last verified
- Jun 2014
- First submitted
- 17 Nov 2009
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01022515
- Acronym / sponsor ID
- PHEO / 2007/081/HP
- Conditions
- Pheochromocytoma, Paraganglioma, Essential Hypertension
- Keywords
- pheochromocytoma, paraganglioma, hypertension
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- Nov 2008
- Primary completion
- 13 Apr 2022 (actual)
- Study completion
- 13 Apr 2022 (actual)
- First posted
- 1 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients with pheochromocytoma | Other | Other: usual follow up with regular EM66 & Cga levels assessmentPatients 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. |
| Patients with essential hypertension | Other | Other: plasma EM66 & CgA levels assessmentPatients 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| plasma EM66 & CgA levels assessmentAfter inclusion checking to eliminate the presence of pheochromocytoma / paraganglioma, a blood sample will be drawn to assess plasma EM66 and CgA levels. | Other | Patients with essential hypertension |
| usual follow up with regular EM66 & Cga levels assessmentPatients 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. | Other | patients with pheochromocytoma |
Primary outcome
Plasma EM66
Time frame: two years
1 secondary outcome
Plasma Chromogranin A levels
Time frame: before treatement
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
Related trials for Pheochromocytoma
RecruitingObservational study
Adrenal Diseases in the Population of Modena: A Clinical-Epidemiological Database of Patients Referred to the Adrenal Disorders Outpatient Clinic of the Clinical Unit of Endocrinology at the Modena University Hospital (AOU Modena)
Cushing s Syndrome, Cushing Disease
Active, not recruitingObservational study
Natural History Study of Children and Adults With Medullary Thyroid Cancer
Medullary Thyroid Cancer
RecruitingObservational study
Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Pheochromocytoma, Paraganglioma
RecruitingObservational study
Von Hippel-Lindau (VHL): Clinical Manifestations, Diagnosis, Management and Molecular Bases of Inherited Renal and Other Urologic Malignant Disorders
Kidney Cancer, Urologic Malignant Disorders
RecruitingPhase 2
Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015)
Pheochromocytoma/Paraganglioma, Pancreatic Neuroendocrine Tumor
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne F Cailleux, MD principal investigator
University Hospital, Rouen
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing plasma EM66 & CgA levels assessment and usual follow up with regular EM66 & Cga levels assessment in people with Pheochromocytoma and Paraganglioma, run by University Hospital, Rouen at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma EM66 (time frame: two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.