Second Study on Cardio-neuromodulation in Humans (CardNMH2)

Different approaches to cardio-neuroablation (CNA) to treat neurally mediated syncope, sinus node dysfunction, and functional atrioventricular block have been published. Investigators have developed a more limited and specific approach of CNA, called cardio-neuromodulation (CardNM). This treatment is based on a tailored vagolysis of the sinoatrial node through partial ablation of the anterior right ganglionated plexus (ARGP); it is also based on an innovative anatomic strategy. The feasibility of CardNM has already been tested in our center in a limited first study in humans (CardNMH1), with a favorable outcome for the patients involved. The results of CardNMH1 have been submitted for publication. The purpose of this second study of CardNM in humans (CardNMH2) is to collect more procedural and clinical data in well-defined patient groups.

Study Overview

• Status: Completed
• Conditions: Syncope; Syncope, Vasovagal; Cardiac Disease; Sick Sinus Syndrome
• Intervention / Treatment: Device: radio-frequency ablation

Detailed Description

This is a phase II A prospective, interventional study. All patients will undergo CardNM. The study will involve eight different steps, from the screening procedure through study completion: screening, enrollment, pharmacological testing, group allocation, preprocedural assessment, procedure, follow-up, study completion.The dedicated study nurse and the PI are responsible for recording all data from the trial on the case report forms (CRFs) and completing the study database. A dedicated independent physician will be responsible for the safety monitoring. The PI will permit inspection of the trial files and the database by national or international official controlling scientific authorities, if required. The PI will review and monitor completed CRFs and the database at regular intervals throughout the trial.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen
    • Bonheiden, Antwerpen, Belgium, 2820
      • Imeldaziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Candidates must meet all of the inclusion criteria required for inclusion in one of the two groups (summarized in Table 2). All of the patients need to have a positive P wave of > 0.5 mm in lead 2. Patients must have had ≥ 1 syncope during the 6 months preceding enrollment and ≥ 2 syncopes in their lifetime except if the last syncope was complicated by an injury or an accident, in which case further waiting for CardNM may be less desirable. Patients < 18 years must have least 3 syncopes with an interval exceeding 1 month unless 1 syncope was complicated by an injury or an accident.

If a significant rate drop (> 15%) is noted during head-up tilt test (HUT), either isolated or combined with vasoplegia, and associated with syncope or severe presyncope, patients will be eligible for inclusion in group A. If the HUT is negative and a pause > 3 seconds has been documented, patients will be assigned to group B. If both conditions are present, patients will be eligible for inclusion in either group but will be preferentially assigned to group A.

Exclusion Criteria:

Candidates will be excluded if ANY of the following criteria apply (detailed in Table 3):

• < 14 years of age;
• Inability to provide consent;
• Chronotropic negative medications (excepted in patients with a previous history of atrial fibrillation);
• 4 g amiodarone intake during the 2 months preceding enrollment;
• Alternating right bundle branch block (RBBB) and left bundle branch block (LBBB), HV interval > 70 ms;
• LBBB, bifascicular block (RBBB + left anterior hemiblock [LAHB], RBBB + left posterior hemiblock [LPHB]);
• PR interval permanently > 240 ms;
• Permanent AF, PAF or electrical cardioversion during the last 6 months;
• Valvular or subvalvular aortic stenosis, mitral stenosis;
• Any unstable medical condition, life expectancy < 12 months;
• Syncopes due a non-cardiac disease (excepted NMS) or advanced neuropathy;
• Current pregnancy;
• glaucoma.

Patients with transient atrioventricular conduction disturbances and normal atrioventricular conduction during an exercise test and normal QRS complexes are eligible for this study.

Patients with a high risk of bleeding are eligible, but clopidogrel (75 mg daily, 1 month of treatment) will then be preferred to oral anticoagulants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with neurally mediated syncope; Tailored radio-frequency ablation of the ARGP (CardNM).	Device: radio-frequency ablation; Patients will undergo a tailored 'radio-frequency ablation' of the ARGP with the Smart Touch™ catheter or with the nMARQ™ catheter. Radiofrequency applications will be interrupted if no significant P-P interval shortening is observed after 30 seconds or if P-P interval is ≤ 550 ms during ablation. The ablation procedure is considered complete when one of the following conditions is fulfilled: P-P interval < 70% baseline procedural P-P interval after 5minute of waiting time; P-P interval < 600 ms after 5 minute of waiting time; 5 radiofrequency applications > 30 seconds have been delivered with the nMARQ™ catheter or 10 applications with the Smart Touch catheter.; Other Names: cardio-neuromodulation, cardio-neuroablation, ARGP
Experimental: Patients with sick sinus syndrome; Tailored radio-frequency ablation of the ARGP (CardNM).	Device: radio-frequency ablation; Patients will undergo a tailored 'radio-frequency ablation' of the ARGP with the Smart Touch™ catheter or with the nMARQ™ catheter. Radiofrequency applications will be interrupted if no significant P-P interval shortening is observed after 30 seconds or if P-P interval is ≤ 550 ms during ablation. The ablation procedure is considered complete when one of the following conditions is fulfilled: P-P interval < 70% baseline procedural P-P interval after 5minute of waiting time; P-P interval < 600 ms after 5 minute of waiting time; 5 radiofrequency applications > 30 seconds have been delivered with the nMARQ™ catheter or 10 applications with the Smart Touch catheter.; Other Names: cardio-neuromodulation, cardio-neuroablation, ARGP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
freedom from syncope	12 months
freedom from serious adverse event	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
freedom from pre syncope	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
quantification of the vagolysis of the sinus node	The quantification of vagolysis of the sinus node obtained during CardNM will be evaluated by automatic P-P interval measurements during procedure, by ECG derived and standardized P-P interval measurements and by automatical quantification of P-P interval histograms on Holter registrations before procedure and during FU.	procedure, 1,3,6,12 months

Collaborators and Investigators

• Sponsor: Imelda Hospital, Bonheiden
• Investigators: Principal Investigator: Philippe Debruyne, MD, Imeldahospital

Publications and helpful links

General Publications

• Debruyne P. "Cardio-Neuromodulation" With a Multielectrode Irrigated Catheter: A Potential New Approach for Patients With Cardio-Inhibitory Syncope. J Cardiovasc Electrophysiol. 2016 Sep;27(9):1110-3. doi: 10.1111/jce.13031. Epub 2016 Aug 1.
• Debruyne P, Rossenbacker T, Janssens L, Collienne C, Ector J, Haemers P, le Polain de Waroux JB, Bazelmans C, Boussy T, Wijns W. Durable Physiological Changes and Decreased Syncope Burden 12 Months After Unifocal Right-Sided Ablation Under Computed Tomographic Guidance in Patients With Neurally Mediated Syncope or Functional Sinus Node Dysfunction. Circ Arrhythm Electrophysiol. 2021 Jun;14(6):e009747. doi: 10.1161/CIRCEP.120.009747. Epub 2021 May 17.
• Debruyne P, Rossenbacker T, Collienne C, Roosen J, Ector B, Janssens L, Charlier F, Vankelecom B, Dewilde W, Wijns W. Unifocal Right-Sided Ablation Treatment for Neurally Mediated Syncope and Functional Sinus Node Dysfunction Under Computed Tomographic Guidance. Circ Arrhythm Electrophysiol. 2018 Sep;11(9):e006604. doi: 10.1161/CIRCEP.118.006604.

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2016
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): May 11, 2020

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 2, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 19, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: ganglionated plexi; syncope; ablation; cardio-neuromodulation; cardio-neuroablation; anterior right ganglionated plexus
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Autonomic Nervous System Diseases; Unconsciousness; Consciousness Disorders; Primary Dysautonomias; Orthostatic Intolerance; Arrhythmia, Sinus; Heart Block; Heart Diseases; Syncope; Syncope, Vasovagal; Sick Sinus Syndrome
• Other Study ID Numbers: B689201629811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No