Genetic Based Analysis in Hypertensive Patients

July 14, 2023 updated by: Roland E. Schmieder, University of Erlangen-Nürnberg Medical School

Genetic Based Analysis of Identifying Predictors of Blood Pressure Response in Hypertensive Patients After Renal Denervation

Many attempts to identify predictors of blood pressure response after renal denervation failed to identify a meaningful determination of blood pressure response.

These attempts have been based on demographic parameters, clinical parameters, endocrine inflammatory and other biochemical variables, comorbidities and disease factors. So far the only predictor of blood pressure response is the pre-treatment blood pressure. According to Wilder's law the pre-treatment baseline value is always a determinant for any change due to an intervention, irrespective which biological variable is examined.

The investigators propose a genetic approach to identify predictors of blood pressure response after renal denervation. Genetic factors are not subject to changes of clinical parameters, previous or current antihypertensive therapy, hypertension associated organ damages, comorbidities and other potential clinical variables.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Background:

Up to now numerous attempts to identify predictors of blood pressure response after renal denervation failed to identify a meaningful and consistent determinant of blood pressure response. These approaches have been based on demographic parameters, clinical parameters, comorbidities and disease factors as well as numerous endocrine inflammatory and other biochemical variables. Only the pre-treatment blood pressure emerged as a predictor of blood pressure response which is no surprise since according to Wilder's law the pre-treatment baseline value is always a determinant for any change due to an intervention, irrespective which biological variable is examined, e.g. blood pressure, LDL cholesterol, HbA1c and so on.

The investigators suggest a genetic approach to identify predictors of blood pressure response after renal denervation. The rationale is quite simple: Genetic factors are not subject to changes of clinical parameters, previous or current antihypertensive therapy, hypertension associated organ damages, comorbidities, and other potential clinical variables. By such an approach the investigators previously were very successful to identify several parameters of modulators hypertensive organ damage that could not have been identified by pathophysiological or pharmaceutical maneuvers. THE INVESTIGATORS PREFER TO RUN A GENOM WIDE ASSOCIATION STUDY AND THE PARTNERS IN GLASGOW AND EDINBURGH HAVE THE DEEP KNOWLWEDGE; EXPERIENCE AND CAPACITY TO RUN A NGS (next generation sequencing, so that's the complete genome)) INCLUDING ALL BIOINFORMATICS AND OTHER ANALYSIS

Objective:

The investigators attempt to identify predictors of blood pressure response to renal denervation by using a GWAS (genome wide association study) approach. This allows to identify various suspected and unexpected polymorphism that are of interest and potentially being strong predictors of blood pressure response. By that approach the investigators will identify novel mechanism of action that are important for blood pressure response (by identifying polymorphism that are beyond the classical thinking how renal denervation may exert blood pressure lowering effects).

Study design:

In collaboration with the Homburg Group (Prof. Dr. Felix Mahfoud), the investigators will extract DNA from stored samples of patients with uncontrolled treatment resistant hypertension and perform a genome wide association study analysis (GWAS) in two cohorts: no/low responders vs. high/excellent responders. NGS will be applied by the partners in Glasgow and Edinburgh. All patients with renal denervation will be categorized according to their pretreatment adjusted blood pressure response and the investigators will compare the upper quartile vs. the lower quartile of all patients that has been so far studied in Homburg and Erlangen. By excluding those patients with a medium or average blood pressure response, the investigators will have two distinct response patterns: low/no response vs. high/excellent response.

By applying standard biostatistics analysis, the investigators will come up with a pattern of polymorphism that are significantly different between the two groups. These identified polymorphisms (or a pattern of it) may be refer, not unexpectedly, to renin angiotensin aldosterone system, sodium and water balance, sympathetic nervous system or other endocrine parameters related to hypertension. In addition to that, the investigators may find significant results of polymorphisms involved in other pathophysiologic pathways not related to hypertension (by our current knowledge) and that the Investigators have not thought about to be related to uncontrolled hypertension. These novel mechanism need to be subsequently further analyzed, but they will offer the opportunity to find novel predictors of blood pressure response.

Study Type

Interventional

Enrollment (Actual)

300

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Erlangen, Germany, 91054
        • Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg
    • Saarland
      • Homburg, Saarland, Germany, 66421
        • Klinik für Innere Medizin III, Kardiologie, Angiologie Und Internistische Intensivmedizin, Saarland University Hospital, Saarland University
  • United Kingdom
    • Scotland
      • Glasgow, Scotland, United Kingdom, G128TA
        • Institute of Cardiovascular and Medical Science

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Individual is ≥ 18 and ≤ 85 years of age.
  • Individual agrees to have all study procedures performed, and is competent and willing to provide written, informed consent to participate in this clinical study
  • Renal denervation ≥ 6 months
  • 24-h ABPM

Exclusion Criteria:

  • Individual has renal artery anatomy that is ineligible for treatment including:

    1. Main renal arteries < 4 mm in diameter or < 20 mm in length.
    2. Hemodynamically or anatomically significant renal artery abnormality or stenosis in either renal artery which, in the eyes of the operator, would interfere with safe cannulation of the renal
    3. A history of prior renal artery intervention including balloon angioplasty or stenting.
    4. Multiple main renal arteries in either kidney.
  • Individual has an estimated glomerular filtration rate (eGFR) of < 45mL/min/1.73m2, using the MDRD calculation.
  • Individual has type 1 diabetes mellitus.
  • Individual has experienced a myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 6 months of the screening visit, or has widespread atherosclerosis, with documented intravascular thrombosis or unstable plaques.
  • Individual has a scheduled or planned surgery or cardiovascular intervention in the next 6 months.
  • Individual has hemodynamically significant valvular heart disease for which reduction of blood pressure would be considered hazardous.
  • Individual has an implantable cardioverter defibrillator (ICD) or pacemaker, or any other metallic implant which is not compatible with magnetic resonance imaging (MRI).
  • Individual has any serious medical condition, which in the opinion of the investigator, may adversely affect the safety and/or effectiveness of the participant or the study (i.e., patients with clinically significant peripheral vascular disease, abdominal aortic aneurysm, bleeding disorders such as thrombocytopenia, hemophilia, or significant anemia, or arrhythmias such as atrial fibrillation).
  • Individual is pregnant, nursing or planning to be pregnant. [Female participants of childbearing potential must have a negative serum or urine human chorionic gonadotropin (hCG) pregnancy test prior to treatment.]
  • Individual has a known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or would be unlikely or unable to comply with study follow-up requirements.
  • Individual is currently enrolled in another investigational drug or device trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Renal Denervation
We attempt to identify predictors of blood pressure response to renal denervation by using a GWAS (Genome wide association study) approch
Genetic: Genetic based analysis of identifying predictors of blood pressure in patients after renal denervation
We attempt to idendtify predictors of blood pressure response to renal denervation by using a GWAS (Genome wide association study) approch.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identifying predictors of systolic blood pressure by 24-h ABPM
Time Frame: 6 months
To identify predictors of systolic blood pressure response after renal denervation as evaluated by 24-h ABPM by using a GWA (genome wide association) approach.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identifying predictors of diastolic blood pressure by 24-h ABPM
Time Frame: 6 months
To identify predictors of diastolic blood pressure response after renal denervation as evaluated by 24-h ABPM by using a GWA (genome wide association) approach.
6 months
Identifying predictors of pulse pressure by 24-h ABPM
Time Frame: 6 months
To identify predictors of pulse pressure response after renal denervation as evaluated by 24-h ABPM by using a GWA (genome wide association) approach.
6 months
Identifying predictors of systolic blood pressure by office blood pressure
Time Frame: 6 months
To identify predictors of systolic blood pressure response after renal denervation as evaluated by office blood pressure by using a GWA (genome wide association) approach.
6 months
Identifying predictors of diastolic blood pressure by office blood pressure
Time Frame: 6 months
To identify predictors of diastolic blood pressure response after renal denervation as evaluated by office blood pressure by using a GWA (genome wide association) approach.
6 months
Identifying predictors of pulse pressure by office blood pressure
Time Frame: 6 months
To identify predictors of pulse pressure response after renal denervation as evaluated by office blood pressure by using a GWA (genome wide association) approach.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Erlangen-Nürnberg Medical School

Investigators

  • Principal Investigator: Roland E Schmieder, MD, University Hospital Erlangen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2019

Primary Completion (Actual)

July 23, 2020

Study Completion (Estimated)

December 31, 2023

Study Registration Dates

First Submitted

February 17, 2020

First Submitted That Met QC Criteria

March 24, 2020

First Posted (Actual)

March 25, 2020

Study Record Updates

Last Update Posted (Actual)

July 17, 2023

Last Update Submitted That Met QC Criteria

July 14, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRC2019GBA

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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