Genetic Based Analysis in Hypertensive Patients

NCT04321044 | Completed DMC

• 1 other identifier: CRC2019GBA
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Hypertension; Renal Denervation; Genetic Predisposition

Keywords

Renal denervation; Arterial hypertension

Outcome Measures

Primary Outcomes (1)

• Identifying predictors of systolic blood pressure by 24-h ABPM

  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 Outcomes (5)

• Identifying predictors of diastolic blood pressure by 24-h ABPM

  6 months

• Identifying predictors of pulse pressure by 24-h ABPM

  6 months

• Identifying predictors of systolic blood pressure by office blood pressure

  6 months

• Identifying predictors of diastolic blood pressure by office blood pressure

  6 months

• Identifying predictors of pulse pressure by office blood pressure

  6 months

Study Arms (1)

Renal Denervation

OTHER

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

Interventions

Genetic based analysis of identifying predictors of blood pressure in patients after renal denervation GENETIC

We attempt to idendtify predictors of blood pressure response to renal denervation by using a GWAS (Genome wide association study) approch.

Renal Denervation

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• h ABPM

You may not qualify if:

• Individual has renal artery anatomy that is ineligible for treatment including:
• Main renal arteries \< 4 mm in diameter or \< 20 mm in length.
• 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
• A history of prior renal artery intervention including balloon angioplasty or stenting.
• 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

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (3)

Klinik für Innere Medizin III, Kardiologie, Angiologie Und Internistische Intensivmedizin, Saarland University Hospital, Saarland University

Homburg, Saarland, 66421, Germany

Location

Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg

Erlangen, 91054, Germany

Location

Institute of Cardiovascular and Medical Science

Glasgow, Scotland, G128TA, United Kingdom

Location

Related Publications (11)

• Messerli FH, Bangalore S, Schmieder RE. Wilder's principle: pre-treatment value determines post-treatment response. Eur Heart J. 2015 Mar 1;36(9):576-9. doi: 10.1093/eurheartj/ehu467. Epub 2014 Dec 23. No abstract available.

  PMID: 25540187 BACKGROUND

• Zolk O, Ott C, Fromm MF, Schmieder RE. Effect of the rs168924 single-nucleotide polymorphism in the SLC6A2 catecholamine transporter gene on blood pressure in Caucasians. J Clin Hypertens (Greenwich). 2012 May;14(5):293-8. doi: 10.1111/j.1751-7176.2012.00618.x. Epub 2012 Apr 9.

  PMID: 22533655 BACKGROUND

• Ott C, Schneider MP, Delles C, Schlaich MP, Hilgers KF, Schmieder RE. Association of (pro)renin receptor gene polymorphism with blood pressure in Caucasian men. Pharmacogenet Genomics. 2011 Jun;21(6):347-9. doi: 10.1097/FPC.0b013e328344cdd2.

  PMID: 21346687 BACKGROUND

• Ritt M, Ott C, Delles C, Schneider MP, Schmieder RE. Impact of the endothelial nitric oxide synthase gene G894T polymorphism on renal endothelial function in patients with type 2 diabetes. Pharmacogenet Genomics. 2008 Aug;18(8):699-707. doi: 10.1097/FPC.0b013e32830500b1.

  PMID: 18622262 BACKGROUND

• Ott C, Schwarz T, Hilgers KF, Kreutz R, Schlaich MP, Schmieder RE. Left-ventricular structure and function are influenced by angiotensinogen gene polymorphism (-20 A/C) in young male patients. Am J Hypertens. 2007 Sep;20(9):974-80. doi: 10.1016/j.amjhyper.2007.03.008.

  PMID: 17765139 BACKGROUND

• Ott C, Titze SI, Schwarz TK, Kreutz R, Hilgers KF, Schmidt BM, Schlaich MP, Schmieder RE. High sodium intake modulates left ventricular mass in patients with G expression of +1675 G/A angiotensin II receptor type 2 gene. J Hypertens. 2007 Aug;25(8):1627-32. doi: 10.1097/HJH.0b013e3281cd40f5.

  PMID: 17620959 BACKGROUND

• Zolk O, Jacobi J, Pahl A, Fromm MF, Schmieder RE. MDR1 genotype-dependent regulation of the aldosterone system in humans. Pharmacogenet Genomics. 2007 Feb;17(2):137-44. doi: 10.1097/01.fpc.0000239969.46594.d0.

  PMID: 17301693 BACKGROUND

• Fromm MF, Schmidt BM, Pahl A, Jacobi J, Schmieder RE. CYP3A5 genotype is associated with elevated blood pressure. Pharmacogenet Genomics. 2005 Oct;15(10):737-41. doi: 10.1097/01.fpc.0000175599.49764.98.

  PMID: 16141800 BACKGROUND

• Hilgers KF, Delles C, Veelken R, Schmieder RE. Angiotensinogen gene core promoter variants and non-modulating hypertension. Hypertension. 2001 Dec 1;38(6):1250-4. doi: 10.1161/hy1201.096545.

  PMID: 11751698 BACKGROUND

• Delles C, Erdmann J, Jacobi J, Hilgers KF, Fleck E, Regitz-Zagrosek V, Schmieder RE. Aldosterone synthase (CYP11B2) -344 C/T polymorphism is associated with left ventricular structure in human arterial hypertension. J Am Coll Cardiol. 2001 Mar 1;37(3):878-84. doi: 10.1016/s0735-1097(00)01174-8.

  PMID: 11693765 BACKGROUND

• Schmieder RE, Erdmann J, Delles C, Jacobi J, Fleck E, Hilgers K, Regitz-Zagrosek V. Effect of the angiotensin II type 2-receptor gene (+1675 G/A) on left ventricular structure in humans. J Am Coll Cardiol. 2001 Jan;37(1):175-82. doi: 10.1016/s0735-1097(00)01063-9.

  PMID: 11153734 BACKGROUND

MeSH Terms

Conditions

Hypertension; Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Roland E Schmieder, MD

  University Hospital Erlangen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor of Medicine

Study Record Dates

• First Submitted: February 17, 2020
• First Posted: March 25, 2020
• Study Start: January 1, 2019
• Primary Completion: July 23, 2020
• Study Completion: December 31, 2023
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); GB (1)