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HypertensionNCT01427049

The Effect of Renal Denervation on Biological Variables

An observational study of Hypertension, run by UMC Utrecht at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypertension
What is being tested?
renal denervation
Type of treatment
Medical device
How many people
54 participants
Where
1 siteNetherlands
Study dates
Aug 2011to Feb 2014
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Individual is currently enrolled in another investigational drug or device trial.
  • Individual is currently being treated with any of the following medications:
  • Drugs that cause salt retention (e.g., systemic corticosteroids and fludrocortisone)
  • Warfarin or phenprocoumon that cannot be temporarily stopped for the procedure.
  • Any contraindications for MRI:
  • The presence of implanted cardiac pacemakers and/or auto-implanted cardioverter defibrillators.
  • Mechanical cardiac valves.
  • Implanted electronic devices like cochlear implants and nerve stimulators.
  • Patients who are unable to fit into the bore of the magnet.
  • Claustrophobia.
  • Prosthesis of a joint.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • UMC Utrecht

    Utrecht, Utrecht

Other trials in Netherlands

About this study

Official title: The Evaluation of Renal Denervation on Several Biological Variables in Patients With Uncontrolled Hypertension. An Observational Feasibility Study.

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.

Read more

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.
Read the detailed description

Objective: The objectives of this study are: the investigation of changes in left ventricular mass (LV mass) after RD using MRI, renal perfusion and renal oxygenation after RD using dynamic contrast enhanced MRI (DCE MRI)and blood oxygenation level dependent MRI (BOLD MRI), the evaluation of safety of RD, in terms of structural changes in the renal arteries and kidney using Magnetic resonance angiography (MRA). Secondly the evaluation of changes in various biological functions assessed by analysis of blood and/or urine samples. Thirdly the quantification of changes in blood pressure. Finally the changes in pulse wave velocity (PWV) and heart rate variability (HRV).

Study design: Observational exploratory-study.

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.

Main study parameters/endpoints: The effect of RD on: radiological variables: left ventricular wall mass, renal perfusion, renal oxygenation and the anatomy of the renal arteries. Secondly the effect of RD on biological variables assessed by analysis of blood and/or urine samples. Thirdly the changes in blood pressure. Finally the changes in PWV and HRV after RD.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risks associated with the tests and procedures performed for the clinical study are limited. There are no known risks associated with MRI when appropriate safety guidelines are followed. Based on the experience form our previous studies, we do not expect any potential risks regarding the cessation of anti-hypertensives.

Conditions
Hypertension
Being tested
renal denervation
Keywords
renal denervation, renal sympathetic denervation, renal ablation, resistant hypertension, hypertension, renal oxygenation, renal perfusion
Medical subject headings
Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • renal denervationDevice

    Also called Symplicity Catheter system

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

Study groups in NCT01427049
Study groupRoleWhat they receive
renal denervationAdults 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.
Receives: Device: renal denervation

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (10)
  1. Radiologic endpoint

    • The change in left ventricular mass -determined by balanced SSFP cine MRI - after renal denervation compared with baseline. This change will be expressed in grams and grams per square meter of body surface area.

    Measured: t=0 and t=12 months

  2. radiologic endpoint

    The change of renal perfusion 12 months after renal denervation compared to baseline. Dynamic contrast-enhanced MRI will be used for quantitative assessment of renal perfusion. Renal perfusion will be calculated in mL/gram/min.

    Measured: t=0 and t=12 months

  3. radiologic endpoint

    The change of renal oxygenation after renal denervation compared to baseline; Changes in oxygenation are calculated in changes in T2 * ratio (i.e. T2 * cortex/ T2 * medulla).

    Measured: t=0 and t=12 months

  4. radiologic endpoint

    • the change in the anatomy of the renal arteries 12 months after renal denervation compared to baseline. for example the existing of renal artery stenosis 12 months after renal denervation compared to baseline: New renal artery stenosis > 60% confirmed by angiogram.

    Measured: t=0 and t=12 months

  5. laboratorial endpoint

    Absolute changes of: eGFR, plasma renin activity (PRA), aldosterone, ACE, lipid spectrum, proteinuria, insulin, C-peptide, glucose, VMA, metanephrines and catecholamines, 12 months after renal denervation compared to baseline measurements

    Measured: t=0 and t=12 months

  6. blood pressure related endpoint

    The effect of renal denervation on the development of orthostatic hypotension

    • The change in the existing of orthostatic hypotension at baseline compared with the existing at 6 and 12 months after renal denervation will be determined

    Measured: t=0 t=6 and t=12 months

  7. blood pressure related endpoint

    The change in the effect of blood pressure, renin and aldosterone in the captopril test 12 months after renal denervation compared with the baseline measurements:

    Change in blood pressure reaction on captopril. Change in the effect of captopril on absolute changes of aldosterone and renin.

    Measured: t=0 and t=12 months

  8. blood pressure related endpoint

    The change in home blood pressure measurements during 12 months after renal denervation

    Measured: measured every month after renal denervation

  9. endpoint derived from investigations at the vascular laboratory

    The in heart rate variability 12 months after renal denervation compared with the baseline measurement

    Change in LF/HF-ratio. Change in LF-power.

    Measured: t=0 and t=12 months

  10. endpoint derived from investigations at the vascular laboratory

    The change of pulse wave velocity 12 months after renal denervation compared with the baseline measurement:

    Change in peripheral pressure pulse waveform. Change in central aortic pressure waveform. Change in Augmentation Index (AI).

    Measured: t=0 and t=12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2011 (estimated)
  2. Study startAug 2011
  3. Primary completionFeb 2014
  4. Study completionFeb 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01427049
Sponsor's protocol ID
11-189
Other IDs
NL35945.041.11
Status last verified
Jan 2017
First submitted
16 Aug 2011
Last updated
2 Feb 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 21505095
  • 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.

    PubMed 21093036
  • 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.

    PubMed 21403086
  • 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.

    PubMed 19444143
  • 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.

    PubMed 19332353
  • 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.

    PubMed 25326543

Questions about this trial

What is this clinical trial studying?

An observational study of Hypertension, run by UMC Utrecht at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Blood pressure related endpoints: (time frame: t=0, t=6 and t=12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01427049, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2017.

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