Clinical trial NCT02856373: Renal Nerve Stimulation and Renal Denervation in Patients With Sympathetic Ventricular Arrhythmias
Official title: Renal Nerve Stimulation and Renal Denervation in Patients With Sympathetic Ventricular Arrhythmias: an Investigator Initiated Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Arrhythmias, Cardiac
Keywords: Denervation
Renal Artery
Lead sponsor: Diagram B.V.
Sponsor class: OTHER
First posted: 2016-08-04
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Rationale:

Sympathetic activity plays an important role in the pathogenesis of ventricular tachyarrhythmia. Previous studies have shown evidence of significant heritable influences on individual responses to adrenergic stimulation. Catheter-based renal sympathetic denervation (RDN) is a novel treatment option for patients with resistant hypertension, proved to reduce local and whole-body sympathetic activity. The investigators hypothesize that percutaneous transluminal electrical stimulation of the sympathetic nerve bundles in the renal arteries will cause ventricular arrhythmias and renal denervation will suppress these arrhythmias in patients with sympathetic ventricular arrhythmias.

Objective:

This study will investigate the effects of renal nerve stimulation before and after percutaneous transluminal RDN on cardiac excitable properties including induction of ventricular tachy-arrhythmias before and after RDN in six studies, i.e. patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome and arrhythmogenic right ventricular cardiomyopathy (ARVC), sympathetically driven ventricular arrhythmias, hypertrophic cardiomyopathy (HCM), dilated non-ischemic cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). The aim of the six studies is to assess the anti-arrhythmic effects of RDN in patients with sympathetic ventricular tachy-arrhythmias.

Study design:

Investigator initiated, multi centre, six pretest-posttest design studies.

Study population:

Patients with recurrent sympathetically driven ventricular arrhythmia despite optimal pharmacological therapy. Patients should be diagnosed with CPVT and certain types of long QT syndrome, ARVC, HCM, DCM and ICM. Eligible patients will be in the age category of 18-85 year.

Intervention:

RDN will be performed according to routine clinical practice. Prior to the ablation procedure, catheter mapping of the renal arteries will be performed according to routine clinical practice. Clinical and biological responses to transluminal electrical renal nerve stimulation will be assessed before and after RDN.

Study endpoints:

* Main procedural study endpoint: Induction of ventricular arrhythmias in response to renal nerve stimulation prior to RDN and absence of renal nerves stimulation induced ventricular arrhythmias after RDN.
* Main clinical study endpoint: Development of ventricular arrhythmia during exercise stress testing performed 6 months after procedure.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

In several studies, it was shown that RDN was safe. The intervention resulted in significantly better control of blood pressure with less medication, and beneficial changes in heart rate variability, autonomic sympathetic balance, renal arteriolar function, and a higher success of atrial fibrillation prevention. In case reports and case series, RDN had a favourable effect in patients with sympathetic drug refractory ventricular tachy-arrhythmias.


Eligibility criteria: Inclusion Criteria:

1. The patient is willing and able to comply with the protocol and has provided written informed consent.
2. The patient falls within the target group as stated in 4.1.
3. Patient is an acceptable candidate for RDN treatment
4. Patient is 18-85 years of age
5. Documentation of ventricular arrhythmia (ECG, rhythm strip or ICD interrogation)

Exclusion Criteria:

1. Contraindication to anticoagulation therapy or heparin.
2. Previous selective cardiac sympathetic denervation or previous RDN procedure.
3. Acute coronary syndrome, cardiac surgery, PCI or stroke within 3 months prior to enrolment.
4. Untreated hypothyroidism or hyperthyroidism.
5. More than grade 1/3 valvular regurgitation and/or significant valve stenosis (moderate or severe).
6. Severe LV dysfunction (LVEF \<20% and/or grade 3/4 diastolic dysfunction).
7. Enrolment in another investigational drug or device study.
8. Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertile age.
9. Mental or physical inability to participate in the study.
10. Planned cardiovascular intervention.
11. Life expectancy ≤ 12 months.
12. Renal artery stenosis \>50% of the arterial lumen, or renal artery lumen ≤3 mm.
13. Complex renal artery

Primary outcomes:
measure: Induction of ventricular arrhythmias (e.g. ventricular tachycardia and ventricular fibrillation)
timeFrame: A few minutes before RDN RNS will be performed. Time frame before RDN: 0-10 min. after RNS and before RDN. Time frame after RDN: 0-10 min.
measure: Development of ventricular arrhythmia
timeFrame: 6 months after procedure/intervention
Secondary outcomes:
measure: Time to first detection of ventricular arrhythmia or appropriate ICD therapy
timeFrame: procedure/intervention-12 month follow up
measure: Changes in ventricular refractoriness (frequency)
timeFrame: procedure/intervention
measure: Changes in ventricular refractoriness (duration)
timeFrame: procedure/intervention
measure: Number of ventricular arrhythmias
timeFrame: procedure/intervention
measure: Ventricular arrhythmia burden
timeFrame: procedure/intervention- 6,12 months follow up
measure: Blood pressure
timeFrame: 6-12 months follow up
measure: Number of (Supra-)Ventricular arrhythmias induced by exercise testing
timeFrame: baseline- 6 months follow up
measure: (Supra-)Ventricular arrhythmias response changes (frequency) induced by exercise testing
timeFrame: baseline- 6 months follow up
measure: (Supra-)Ventricular arrhythmias response changes (duration) induced by exercise testing
timeFrame: baseline- 6 months follow up
measure: Changes in heart rate variability
timeFrame: baseline- 3, 6 and 12 month follow up
measure: Changes in prevalence of events
timeFrame: 12 month before procedure/intervention-12 month follow up
measure: Change in blood pressure
timeFrame: baseline- 6, 12 month follow up
measure: Heart rate response changes induced by exercise testing
timeFrame: baseline- 6 months follow up
measure: Blood pressure response changes induced by exercise testing
timeFrame: baseline-6 months follow up
Other outcomes:
Locations:
city: Zwolle
country: Netherlands
facility: A. Elvan
state: Overijssel
Study officials:
affiliation: Isala, department of Cardiology
name: Arif Elvan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: