Omics Signature in the Diagnosis of Hypertension (ENSAT-HT)

Performance of an Omics-signature in the Diagnosis and Prognosis of Endocrine and Primary Hypertension

The purpose of this study is to assess the validity and usefulness of omics signatures for improved identification and risk stratification of patients with endocrine hypertension and stratification of patients with primary hypertension.

Study Overview

• Status: Unknown
• Conditions: Hypertension
• Intervention / Treatment: Other: omics

Detailed Description

Arterial hypertension is the most important cause of death in the world. At referral hypertension centers about 25% of patients have a single cause for hypertension, so-called secondary hypertension, mostly of endocrine, adrenal origin (primary aldosteronism, pheochromocytoma/ paraganglioma, Cushing's syndrome). This rate steps up to 50% in patients with drug resistant hypertension. Proper treatment of secondary hypertension improves prognosis considerably but depends on adequate diagnosis. Classically the diagnosis of such forms of hypertension rests on cumbersome biochemical and imaging procedures that may not completely take away uncertainty. Modern '-omics' techniques (genomics, metabolomics, proteomics of plasma and urine) may allow faster and better diagnosis. In addition, they may provide a basis for stratification of hypertensive patients that do not have a identifiable cause of hypertension, so-called primary hypertension. This stratification may help predicting response to antihypertensive drugs and determining prognosis and thus, help to establish personalized medicine in hypertension care.

• Study Type: Observational
• Enrollment (Anticipated): 4000

Contacts and Locations

• Study Contact: Name: Laurence Amar, PD PhD; Phone Number: +33156093771; Email: laurence.amar@aphp.fr
• Study Contact Backup: Name: Jaap Deinum, MD PhD; Phone Number: +31 24 3618819; Email: jaap.deinum@radboudumc.nl

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • European Georges Pompidou Hospital
    • Contact: Laurence Amar, MD, PhD; Phone Number: 33156093771; Email: laurence.amar@aphp.fr
    • Contact: Michel Azizi, PD, PhD; Phone Number: 33156093771; Email: michel.azizi@aphp.fr
• Italy
  • Padua, Italy
    • Not yet recruiting
    • University of Padua
    • Contact: Gian Paolo Rossi
  • Torino, Italy
    • Not yet recruiting
    • University of Torino
    • Contact: Paolo Mulatero
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • Raddboudumc
      • Contact: Joyce Koffeman, MSc.; Phone Number: +31 24 3618819; Email: joyce.koffeman-smeltink@radboudumc.nl
      • Principal Investigator: Jaap Deinum, MD PhD
• United Kingdom
  • Glasgow, United Kingdom
    • Not yet recruiting
    • University of Glasgow
    • Contact: Eleonore Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects referred for diagnosis and management of hypertension

Description

Inclusion Criteria:

• Aged from 18 to 75 years old
• A signed and dated informed consent form

• A diagnosis of hypertension defined either as:

  • Use of antihypertensive drug (s)
  • Arterial hypertension: in untreated patients this must be confirmed by daytime ambulatory blood pressure monitoring (ABPM), or home blood pressure monitoring, with blood pressure higher or equal to 135 mmHg for systolic blood pressure and/or higher or equal to 85 mmHg for diastolic blood pressure.

In order to be eligible to participate in the nested case control study, a subject must also meet the following criteria:

- A conformed diagnosis of PA, PPGL or CS for case patients and PHT (exclusion of secondary forms) for their matched counterparts

Exclusion Criteria:

• Any severe comorbid conditions that, according to the attending physician, could decrease the life expectancy to less than 3 years
• Any active malignancy unrelated to adrenal disease or PPGL
• Guardianship for incapacity

A potential control subject who meets any of the following criteria will be excluded from participation in the nested case controlled study in case of:

• Existence of any other forms of secondary hypertension such as renal artery stenosis, renal disease, Munchausen's syndrome in which the patient induces hypertension regardless of method.
• Drug-induced (included factitious use of illicit substances) hypertension

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hypertensive patients; Diagnostic procedures in patients with hypertension applying omics results	Other: omics; diagnostic procedures applying omics results

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sensitivities of omics signatures for the diagnosis of subtypes of hypertension	The proportion of patients with various subtypes of endocrine hypertension as identified by omics signature in patients in which subtypes have been identified by usual diagnostic algorithms	1 year
specificities of omics signatures for the diagnosis of subtypes of hypertension	The proportion of patients with non-endocrine hypertension as identified by omics signature in patients identified as having non-endocrine hypertension by usual diagnostic algorithms.	1 year
positive likelihood ratio	positive likelihood ratios of omics signatures for the diagnosis of subtypes of hypertension	1 year
negative likelihood ratio	negative likelihood ratios of omics signatures for the diagnosis of subtypes of hypertension	1 year
positive predictive value	positive predictive values of omics signatures for the diagnosis of subtypes of hypertension	1 year
negative predictive value	negative predictive values of omics signatures for the diagnosis of subtypes of hypertension	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of major adverse cardiovascular events (MACE)	death, myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) or need for them, cerebrovascular accident (CVA), hospitalization for acute decompensated heart failure	within 12 months after baseline
Left ventricular mass as assessed by echocardiography	Left ventricular mass index measured by ultrasound imaging	1 year
Costs	Questionnaires on costs of evaluation, costs of misdiagnosis	1 year
Ambulatory blood pressure measurement (ABPM)	ABPM	1 year
microalbuminuria	albumin-creatinine ratio in urine	1 year
atrial fibrillation	atrial fibrillation as assessed by EKG	1 year
RAND-36	Quality of life assessment by the RAND-36 questionnaire	1 year
EQ5D	Quality of life assessment by the EQ5D questionnaire	1 year
Hospital Anxiety and Depression Scale (HADS)	Assessment of anxiety and depression by the HADS questionnaire	1 year
Cognitive Functioning Questionnaire (CFQ)	Assessment of cognitive functioning by CFQ	1 year
Montreal Cognitive Assessment (MOCA)	Assessment of cognitive functioning by MOCA	1 year
Home blood pressure measurement (HBPM)	HBPM	1 year
number of antihypertensive drugs	number of antihypertensive drugs	1 year
defined daily dosages	defined daily dosages of antihypertensive drugs	1 year

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: University of Padova; University of Turin, Italy; University of Glasgow; European Georges Pompidou Hospital
• Investigators: Principal Investigator: Maria Christina Zennaro, PhD, AP/HECP, Paris

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): May 1, 2019

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: May 12, 2016
• First Posted (Estimate): May 13, 2016

Study Record Updates

• Last Update Posted (Estimate): January 26, 2017
• Last Update Submitted That Met QC Criteria: January 25, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: genomics; primary aldosteronism; metabolomics; proteomics; pheochromocytoma; endocrine hypertension; Cushing syndrom
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: ENSAT-HT-2016-01