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Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas (CHIRACIC)

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ClinicalTrials.gov Identifier: NCT02364089
Recruitment Status : Recruiting
First Posted : February 16, 2015
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:
The general objective is to evaluate the consequences of surgical removal of SCSI on hypertension and cardiovascular risk factors in order to determine on an evidence-based basis if surgical excision of SCSI is preferable to an intensive medical regimen in patients with hypertension.

Condition or disease Intervention/treatment Phase
Adrenal Incidentalomas Procedure: Laparoscopic surgical removal of the adrenal tumor Drug: Standardized medical treatment of hypertension by SAHR Not Applicable

Detailed Description:

Adrenal incidentalomas are unsuspected adrenal masses found during abdominal imaging. With the widespread use of computed tomography and MRI, adrenal incidentalomas are found in approximately 2% of patients. In an endocrinology setting, the majority of these masses are benign adenomas of the adrenal cortex. Approximately 10% of these adenomas display little excess of cortisol secretion associated to some degree of secretory autonomy but that are insufficient to generate overt Cushing's syndrome ("Subclinical Secreting Cortisol incidentalomas" or SCSI). However, hypertension and to a lesser degree obesity and impaired glucose tolerance are very frequent amongst patients with SCSI. The hypothesis that the mild hypercortisolism associated with SCSI is responsible for these clinical consequences is substantiated by few studies describing improvement after resection of SCSI. However, these studies were retrospective, uncontrolled and suffered from imprecision and numerous methodological bias. Thus, whether surgery is more beneficial than medical treatment is currently unknown and there is no consensus on the appropriate treatment for SCSI.

Patient selection Run-In period. Discontinuation of previous antihypertensive treatments and prescription of a standardized anti-hypertensive drug regimen (SAHR). Monthly Blood Pressure (BP) measurement using home BP monitoring. The duration of the Run-In periods will be ≤ 6 months and will end when BP will be controlled with the SAHR at two consecutive visits.

End of RI Second endocrine assessment for eligibility Randomization (Ra): 24h Ambulatory BP measurement, anthropometric and metabolic evaluation. Quality of life and cognition questionnaires. Randomization in 2 groups : Gr 1 Treatment group : Surgery followed by intensive medical care ; Gr 2 : Control Group : intensive medical care only.

Ra + 1Mo: Surgery in Group 1 Ra + 2.5 Mo to Ra + 13 Mo: 6 weeks interval follow-up Evaluation of home BP monitoring and adaptation of the SAHR. A step by step reduction of the SAHR will be attempted in the two patient groups at Ra+2.5Mo. A second attempt will systematically be performed in both groups at Ra+8.5 Medical evaluation of associated metabolic conditions (obesity, diabetes, dyslipidemia) and adaptation of treatments Record of medical events and side effects of treatments Ra + 13Mo: Final evaluation. Endocrine assessment. 24h Ambulatory BP measurement, anthropometric and metabolic evaluation. Quality of life and cognition questionnaires.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas
Actual Study Start Date : April 2015
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Surgery followed by intensive medical care
Laparoscopic surgical removal of the adrenal tumor
Procedure: Laparoscopic surgical removal of the adrenal tumor
Active Comparator: Intensive medical treatment only
Standardized medical treatment of hypertension by SAHR.
Drug: Standardized medical treatment of hypertension by SAHR

Standardized anti-hypertensive drug regimen has been established according to international recommendations and includes the following steps:

  • step 1: Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin II receptor antagonist (ARBs) at half-dose (Ranipril 5mg or Ibesartan 150 mg )
  • step 2: CEI or ARA2 at full dose (Ranipril 10 mg or Ibesartan 300 mg)
  • step 3: Add-on of Amlodipine 10 mg or Diltiazem LP 300 mg
  • step 4: Add-on of Indapamide LP 1.5 mg
  • step 5: Add-on of Spironolactone 25 mg
  • step 6: Add-on of Bisoprolol 10 mg
  • step 7: Add-on of Prazosine LP 5mg/day.




Primary Outcome Measures :
  1. Blood pressure value and SAHR step 12 months after inclusion [ Time Frame: 12 months ]
    Treatment response will defined as a reduction of at least 1 step of SAHR at the end of the study, with BP maintained within the study objectives (125-135 mm Hg systolic and 75-85 mm Hg diastolic) according to self-measurement at home.


Secondary Outcome Measures :
  1. Antihypertensive treatment score and daily drug dose [ Time Frame: 12 months ]
  2. Incidence of complications in the two strategies. [ Time Frame: 12 months ]
  3. Direct costs of the two strategies. [ Time Frame: 12 months ]
  4. Assessment of predictive factors for the success of surgery on BP [ Time Frame: 12 months ]
    age, family history of hypertension, duration of hypertension, kidney function, biochemical endocrine abnormalities, urinary steroid profile

  5. number of patients requiring antihypertensive treatment [ Time Frame: 12 months ]
  6. 24 hours ambulatory blood pressure monitoring values [ Time Frame: At inclusion (day 0) and at 12 months ]
  7. Blood glucose and lipid lowering agents values [ Time Frame: 12 months ]
  8. Cardiovascular risk factors/markers level [ Time Frame: 12 months ]
    Comparison of the two therapeutic strategies with regard to cardiovascular risk factors/markers: BMI, body composition evaluated by DEXA, abdominal fat evaluated on CT-scan, fasting blood glucose and insulin, HbA1C, HOMA-IR (homeostasis model of assessment of insulin resistance) and OGTT (oral glucose tolerance test), blood lipids, pro-inflammatory adipokines

  9. Number of patients with persistent diabetes, dyslipidemia and metabolic syndrome [ Time Frame: 12 months ]
  10. Evaluation of quality of life [ Time Frame: At inclusion and 12 months ]
    Comparison of the two therapeutic strategies with regard to quality of life



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≤ 80 years.
  • Incidentally discovered unilateral SCSI:

    • Adrenocortical tumor on CT (spontaneous density < 20 HU and/or relative wash-out > 40%, absolute wash-out > 60% ) and > 2 cm in size.
    • Impaired DST (cortisol > 138 nmol/L or 5 µg/dL)

OR

• Impaired DST (cortisol > 50 83 nmol/L or 1,8 3 µg/dL) AND one biological abnormality of the corticotropic axis at study entry:

  • 8 a.m. plasma ACTH < 2.2 pmol/L (10 pg/ml),
  • In case of ACTH at 8 a.m. between 10 and 20 pg/mL (2.2 and 4.4 pmol/L), peak of ACTH < 30 pg/mL (6.6 pmol/L) after a CRH test
  • midnight cortisol > 150 nmol/L (5.4 µg/dL)
  • elevated late-evening salivary cortisol according to the range of the assay
  • increased 24-hour free urinary cortisol but <2.0-fold the laboratory upper normal limit.
  • Systolic or diastolic hypertension treated

OR

  • Systolic or diastolic hypertension (> 135/85 mmHg) not treated assessed on standard blood pressure self-measurement device.
  • Written informed consent signed by patient and investigator

Exclusion Criteria:

  • Age > 80 years.
  • Bilateral incidentaloma.
  • Incidentally adrenocortical tumor < 2 cm
  • History of myocardial infarction, pulmonary edema or stroke during the previous year
  • Malignant hypertension (> 175-115 mm Hg on self-measurement)
  • Beta-blocker treatment that cannot be suspended.
  • Free urinary cortisol > 2.0-fold upper normal limit
  • 08h00 plasma ACTH concentration > 4.4 pmol/L (20 pg/ml)
  • Chronic renal insufficiency (clearance < 30 mL/min)
  • Exogenous corticosteroid treatment by general or local route (inhaled, eye or ear drops , ophthalmic ointment, topical skin application, ear infiltration) during the 6 months before the trial

OR

• Need for Corticosteroid treatment

OR

• Medication interfering with dexamethasone metabolism.(54)

  • Pregnancy
  • Life-threatening pathology (in the short term)
  • Contra-indications to surgery
  • Lack of control of blood pressure at the end of the Run-In period
  • Dissipation of the biological endocrine criteria for SCSI at the end of the Run-In period

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): NCT02364089


Contacts
Contact: Antoine TABARIN, Professor +33 5 57 65 64 33 antoine.tabarin@chu-bordeaux.fr
Contact: Sarah CAZENAVE +33 5 57 65 62 77 sarah.cazenave@chu-bordeaux.fr

Locations
France
Service de Médecine Interne, Endocrinologie et Nutrition - CHU de Strasbourg Recruiting
Strasbourg, Alsace, France, 67000
Contact: Bernard GOICHOT, Professor    +33 3 88 12 75 93    Bernard.Goichot@chru-strasbourg.fr   
Service Endocrinologie, Diabétologie, maladies métaboliques - CHU de Bordeaux Recruiting
Pessac, Aquitaine, France, 33600
Contact: Antoine TABARIN, Professor    +33 5 57 65 64 33    antoine.tabarin@chu-bordeaux.fr   
Contact: Sarah CAZENAVE    +33 5 57 65 62 77    sarah.cazenave@chu-bordeaux.fr   
Service d'Endocrinologie - Niveau 18 - Caen CHU Côte de Nacre Recruiting
Caen, Basse-Normandie, France, 14000
Contact: Yves REZNIK, Professor    +33 2 31 06 45 86    reznik-y@chu-caen.fr   
Service d'Endocrinologie -Diabète-Nutrition - CHU de REIMS Not yet recruiting
Reims, Champagne-Ardenne, France, 51000
Contact: Brigitte DELEMER, Doctor    +33 3 26 78 81 01    bdelemer@chu-reims.fr   
Service d'Endocrinologie, Diabétologie, Nutrition - CHU d'Amiens Not yet recruiting
Amiens, Haut De France, France, 80000
Contact: Rachel DESAILLOUD, Pr    03.22.45.58.97 ext +33    Desailloud.Rachel@chu-amiens.fr   
Endocrinologie, Diabète et Maladies Métaboliques - CHU de Rouen Not yet recruiting
Rouen, Haute-Normandie, France, 76000
Contact: Hervé LEFEBVRE, Professor    +33 2 32 88 90 81    Herve.Lefebvre@chu-rouen.fr   
Service d'Endocrinologie et des Maladies de la Reproduction- Assistance Publique - Hôpitaux de Paris - Hôpial Bicêtre Recruiting
Le Kremlin Bicêtre, ILE DE France, France, 94275
Contact: Jacques YOUNG       jacques.young@bct.ap-hop-paris.fr   
Assistance Publique - Hôpitaux de Paris - Hôpital COCHIN Recruiting
Paris, ILE DE France, France, 75014
Contact: Jérôme BERTHERAT, Professor    +33 1 58 41 18 95    jerome.bertherat@ch.aphp.fr   
Service d'Endocrinologie et Gynécologie - Assistance Publique - Hôpitaux de Paris - Pitié-Salpêtrière Withdrawn
Paris, ILE DE France, France, 75651
Service d'Hypertension et de Médecine Vasculaire - Assistance Publique - Hôpitaux de Paris - Hôpital européen Georges Pompidou Recruiting
Paris, ILE DE France, France, 75908
Contact: Pierre-François PLOUIN, Professor    +33 1 56 09 37 71    pierre-francois.plouin@egp.aphp.fr   
Service d'Endocrinologie - Saint-Antoine - AP-HP Not yet recruiting
Paris, Ile De France, France
Contact: Sophie CHRISTIN-MAITRE, Pr    01.49.28.24.10 ext +33    sophie.christin-maitre@aphp.fr   
Service d'Endocrinologie - CHU de Nancy Withdrawn
Nancy, Lorraine, France, 54000
Service d'Endocrinologie et Maladies Métabolique - CHU de Toulouse Recruiting
Toulouse, Midi-Pyrénées, France, 31000
Contact: Philippe CARON, Professor    +33 5 67 77 17 01    caron.p@chu-toulouse.fr   
Service d'Endocrinologie, Diabétologie et Métabolisme - CHRU de LILLE Recruiting
Lille, Nord-Pas-de-Calais, France, 59000
Contact: Marie-Christine VANTYGHEM, Professor    +33 3 20 44 45 35    mc-vantyghem@chru-lille.fr   
Département Endocrinologie-Diabétologie -Nutrition - CHU d'ANGERS Recruiting
Angers, Pays De La Loire, France, 49000
Contact: Sandrine LABOUREAU-SOARES, Doctor    +33 2 41 35 45 93    sasoares@chu-angers.fr   
CIC Endocrinologie-Nutrition - CHU de Nantes Recruiting
Nantes, Pays De La Loire, France, 44000
Contact: Bertrand CARIOU, Professor    +33 2 53 48 27 07    bertrand.cariou@univ-nantes.fr   
Service d'Endocrinologie, Diabète et Maladies Métaboliques - Assistance publique - Hôpitaux de Marseille Recruiting
Marseille, Provence-Alpes-Côte d'Azur, France, 13000
Contact: Thierry BRUE, Professor    +33 4 91 38 65 97    Thierry.BRUE@ap-hm.fr   
Service Endocrinologie - CHU de Saint-Etienne Withdrawn
Saint-Etienne, Rhône-Alpes, France, 42000
CHU de Poiriers Not yet recruiting
Poitiers, France, 86021
Contact: Mathilde FRATY, Dr       mathilde.fraty@chu-poitiers.fr   
Germany
Endokrinologie, Diabetes und Ernährungsmedizin, Campus Mitte, Medizinische Klinik - Charité - Universitätsmedizin Berlin Not yet recruiting
Berlin, Germany, 10117
Contact: Tina Kienitz       tina.kienitz@charite.de   
Medizinische Klinik und Poliklinik IV, Endocrine Research Unit - Ludwig-Maximilians-Universität Not yet recruiting
München, Germany, 80336
Contact: Felix Beuschlein       Felix.Beuschlein@med.uni-muenchen.de   
Department of Internal Medicine I, Endocrine and Diabetes Uni -University Hospital Würzburg Recruiting
Würzburg, Germany, 97080
Contact: Martin FAßNACHT, Pr       Fassnacht_M@ukw.de   
Italy
Clinica di Endocrinologia e Malattie del Metabolismo, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona Not yet recruiting
Ancona, Italy
Contact: Giorgio Arnaldi       Giorgio.Arnaldi@ospedaliriuniti.marche.it   
S Orsola-Malpighi Hospital Recruiting
Bologna, Italy, 40138
Contact: Uberto Pagotto       uberto.pagotto@unibo.it   
University-Hospital of Padova Not yet recruiting
Padova, Italy, 35128
Contact: Carla Scaroni       carla.scaroni@unipd.it   
"Casa Sollievo della Sofferenza" Hospital Not yet recruiting
San Giovanni Rotondo, Italy, 71013
Contact: Alfredo Scillitani       endocrino@operapadrepio.it   
Dipartimento di Scienze Cliniche e Biologiche, Università degli Studi di Torino Not yet recruiting
Torino, Italy, 10043
Contact: Massimo Terzolo       massimo.terzolo@unito.it   
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Study Chair: Paul PEREZ, Doctor University Hospital, Bordeaux

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT02364089     History of Changes
Other Study ID Numbers: CHUBX 2012/34
First Posted: February 16, 2015    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018

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

Keywords provided by University Hospital, Bordeaux:
Adrenal Incidentaloma
Subclinical Cushing's syndrome
Hypertension
Cardiovascular Risk Factors
Metabolic Syndrome
Surgery of adrenal tumor

Additional relevant MeSH terms:
Adrenocortical Adenoma
Adrenal Gland Neoplasms
Adrenal Cortex Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Adrenal Cortex Diseases
Adrenal Gland Diseases
Endocrine System Diseases
Epinephrine
Racepinephrine
Epinephryl borate
Hydrocortisone
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents
Anti-Inflammatory Agents