Clinical trial NCT02772315: Omics Signature in the Diagnosis of Hypertension
Official title: Performance of an Omics-signature in the Diagnosis and Prognosis of Endocrine and Primary Hypertension
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hypertension
Keywords: genomics
proteomics
metabolomics
endocrine hypertension
primary aldosteronism
Cushing syndrom
pheochromocytoma
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: European Georges Pompidou Hospital
name: University of Turin, Italy
name: University of Padova
name: University of Glasgow
First posted: 2016-05-13
Enrollment: 4000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects referred for diagnosis and management of hypertension

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: sensitivities of omics signatures for the diagnosis of subtypes of hypertension
timeFrame: 1 year
measure: specificities of omics signatures for the diagnosis of subtypes of hypertension
timeFrame: 1 year
measure: positive likelihood ratio
timeFrame: 1 year
measure: negative likelihood ratio
timeFrame: 1 year
measure: positive predictive value
timeFrame: 1 year
measure: negative predictive value
timeFrame: 1 year
Secondary outcomes:
measure: Occurrence of major adverse cardiovascular events (MACE)
timeFrame: within 12 months after baseline
measure: Left ventricular mass as assessed by echocardiography
timeFrame: 1 year
measure: Costs
timeFrame: 1 year
measure: Ambulatory blood pressure measurement (ABPM)
timeFrame: 1 year
measure: microalbuminuria
timeFrame: 1 year
measure: atrial fibrillation
timeFrame: 1 year
measure: RAND-36
timeFrame: 1 year
measure: EQ5D
timeFrame: 1 year
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 1 year
measure: Cognitive Functioning Questionnaire (CFQ)
timeFrame: 1 year
measure: Montreal Cognitive Assessment (MOCA)
timeFrame: 1 year
measure: Home blood pressure measurement (HBPM)
timeFrame: 1 year
measure: number of antihypertensive drugs
timeFrame: 1 year
measure: defined daily dosages
timeFrame: 1 year
Other outcomes:
Locations:
city: Paris
country: France
facility: European Georges Pompidou Hospital
city: Padua
country: Italy
facility: University of Padua
city: Torino
country: Italy
facility: University of Torino
city: Nijmegen
country: Netherlands
facility: Raddboudumc
state: Gelderland
city: Glasgow
country: United Kingdom
facility: University of Glasgow
Study officials:
affiliation: AP/HECP, Paris
name: Maria Christina Zennaro, PhD
role: PRINCIPAL_INVESTIGATOR
References: