The Effect of Renal Denervation on Biological Variables

NCT01427049 | Completed DMC

• 2 other identifiers: 11-189NL35945.041.11
• Study Type: observational
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Hypertension is a major and growing public health concern. Chronic elevation of sympathetic nervous system (SNS) activity has been identified as a major contributor to the complex pathophysiology of (essential) hypertension. The renal sympathetic nerves play a major role in the elevation of the SNS activity. Therapeutic renal denervation (RD), the deliberate disruption of the nerves connecting the kidneys with the central nervous system, has been shown to be an effective means of modulating elevated SNS activity - both by reducing the sympathetic modulation of renal function (renin release, sodium excretion and renal blood flow) and by removing the renal afferent sympathetic contribution to central blood pressure elevation. This current study is an observational exploratory study. The main objective of this study is to learn more on the effects of RD. We wish to do that by quantifying the effects of RD on various biological variables. Those variables are studied in four sets of investigations: a radiological set, a laboratorial set, a set of blood pressure measurements and a set of investigations in the vascular laboratory. The radiological set consists of imaging of the heart and kidney function (renal perfusion) and structure (renal arteries), the laboratorial set of serum and urine tests, 24 h- home- and office- blood pressure measurements will be taken and finally the set of vascular tests contains investigations on pulse wave velocity(PWV) and heart rate variability(HRV). The data will most likely help us to define future studies, to describe the mode of action and the effects of RD on various organs and systems in more detail, and finally to define in more detail which type of hypertensive patients is especially likely to benefit of the procedure. Hypothesis:

• We hypothesize that LV mass will decrease after RD. Because all patients have severe hypertension, it is likely that a substantial percentage will have increased LV mass.
• We hypothesize that renal perfusion and renal oxygenation increase after RD.
• We hypothesize that there will be no complications related to the device or procedure.
• We hypothesize that renal denervation has a beneficial effect on insulin resistance
• We hypothesize that renal denervation will decrease the blood pressure(office and 24-hour-measurements)
• We hypothesize that RD has a beneficial effect on PWV and HRV.

Conditions

Hypertension

Keywords

renal denervation; renal sympathetic denervation; renal ablation; resistant hypertension; hypertension; renal oxygenation; renal perfusion

Outcome Measures

Primary Outcomes (1)

• Change in Blood pressure related endpoints:

  * Incidence of achieving target systolic blood pressure(SBP) (SBP \<140 mmHg, or \<130 for diabetics) * Incidence of achieving a \>10 mmHg reduction in SBP * Change in office BP from baseline to 6 months post-renal denervation. * Change in 24 hour ambulatory blood pressure taken without the use of antihypertensive medication, from baseline to 12 months post-renal denervation. * Changes in SBP and diastolic blood pressure (DBP) from baseline to 6 and 12 months

  t=0, t=6 and t=12 months

Secondary Outcomes (10)

• Radiologic endpoint

  t=0 and t=12 months

• radiologic endpoint

  t=0 and t=12 months

• radiologic endpoint

  t=0 and t=12 months

• radiologic endpoint

  t=0 and t=12 months

• laboratorial endpoint

  t=0 and t=12 months

Study Arms (1)

renal denervation

Adults with a systolic BP ≥160 mmHg (≥150 mmHg for type 2 diabetics) with a stable drug regimen including 3 or more antihypertensive medications, including a diuretic, or inability to follow a stable drug regimen due to unacceptable side-effects of antihypertensive medication.

Device: renal denervation

Interventions

renal denervation DEVICE

percutaneous selective renal sympathetic denervation with the use of the Symplicity Catheter system

Also known as: Symplicity Catheter system

renal denervation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with a systolic BP ≥160 mmHg (≥150 mmHg for type 2 diabetics) with a stable drug regimen including 3 or more antihypertensive medications, including a diuretic, or inability to follow a stable drug regimen due to unacceptable side-effects of antihypertensive medication. This current study is an observational exploratory-study.

You may qualify if:

• Individual has a systolic BP ≥160 mmHg (≥150 mmHg for type 2 diabetics) based on an average of 3 office BP readings measured according to the guidelines in appendix A.
• Individual is adhering to a stable drug regimen including 3 or more antihypertensive medications, including a diuretic (with no changes for a minimum of 2 weeks prior to enrolment) which is expected to be maintained for at least 6 months. Or:
• Has experienced side effects to several anti-hypertensive medications
• Individual is ≥18 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.

You may not qualify if:

• Individual has a treatable secondary cause of hypertension. (it is possible that during baseline procedures secondary causes of hypertension are discovered, those individuals will be excluded from participation of the study.)
• 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 artery or meets standards for surgical repair or interventional dilation.
• A history of prior renal artery stenting.
• Multiple main renal arteries in either kidney.
• Individual has an estimated glomerular filtration rate (eGFR) of \<30mL/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 scheduled or planned surgery or cardiovascular intervention in the next 6 months.
• Individual has hemodynamically significant valvular heart disease for which reduction of BP would be considered hazardous.
• Individual has an implantable cardioverter defibrillator (ICD) or pacemaker whose settings cannot allow for RF energy delivery.
• 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, haemophilia, or significant anaemia, or arrhythmias such as atrial fibrillation).
• Individual is pregnant, nursing or planning to be pregnant.
• 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.

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

UMC Utrecht

Utrecht, Utrecht, Netherlands

Location

Related Publications (6)

• Blankestijn PJ, Ritz E. Renal denervation: potential impact on hypertension in kidney disease? Nephrol Dial Transplant. 2011 Sep;26(9):2732-4. doi: 10.1093/ndt/gfr190. Epub 2011 Apr 19. No abstract available.

  PMID: 21505095 BACKGROUND

• Symplicity HTN-2 Investigators; Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Bohm M. Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet. 2010 Dec 4;376(9756):1903-9. doi: 10.1016/S0140-6736(10)62039-9. Epub 2010 Nov 17.

  PMID: 21093036 BACKGROUND

• Symplicity HTN-1 Investigators. Catheter-based renal sympathetic denervation for resistant hypertension: durability of blood pressure reduction out to 24 months. Hypertension. 2011 May;57(5):911-7. doi: 10.1161/HYPERTENSIONAHA.110.163014. Epub 2011 Mar 14.

  PMID: 21403086 BACKGROUND

• Siddiqi L, Joles JA, Grassi G, Blankestijn PJ. Is kidney ischemia the central mechanism in parallel activation of the renin and sympathetic system? J Hypertens. 2009 Jul;27(7):1341-9. doi: 10.1097/HJH.0b013e32832b521b.

  PMID: 19444143 BACKGROUND

• Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham WT, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009 Apr 11;373(9671):1275-81. doi: 10.1016/S0140-6736(09)60566-3. Epub 2009 Mar 28.

  PMID: 19332353 BACKGROUND

• Verloop WL, Vink EE, Spiering W, Blankestijn PJ, Doevendans PA, Bots ML, Vonken EJ, Voskuil M, Leiner T. Effects of renal denervation on end organ damage in hypertensive patients. Eur J Prev Cardiol. 2015 May;22(5):558-67. doi: 10.1177/2047487314556003. Epub 2014 Oct 17.

  PMID: 25326543 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

serum

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Peter Blankestijn, Dr.

  UMC Utrecht department of Nephrology and Hypertension

  PRINCIPAL INVESTIGATOR

• Eva Vink, PhD Student

  UMC Utrecht Department of Nephrology and Hypertension

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: August 16, 2011
• First Posted: September 1, 2011
• Study Start: August 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: February 2, 2017

Record last verified: 2017-01

Locations

NL (1)