Second Study on Cardio-neuromodulation in Humans (CardNMH2)

• Sponsor: Imelda Hospital, Bonheiden
• Information provided by (Responsible Party): Philippe Debruyne, Imelda Hospital, Bonheiden

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cardiac Disease; Syncope; Syncope, Vasovagal; Sick Sinus Syndrome	Device: radio-frequency ablation (nMARQ™ or Smart Touch™ catheter)	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Second Study on Cardio-neuromodulation in Humans
Study Start Date :	December 2016
Estimated Primary Completion Date :	June 2018
Estimated Study Completion Date :	December 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Patients with neurally mediated syncope; Tailored radio-frequency ablation of the ARGP (CardNM).	Device: radio-frequency ablation (nMARQ™ or Smart Touch™ catheter); 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 Name: cardio-neuromodulation, cardio-neuroablation, ARGP
Experimental: Patients with sick sinus syndrome; Tailored radio-frequency ablation of the ARGP (CardNM).	Device: radio-frequency ablation (nMARQ™ or Smart Touch™ catheter); 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 Name: cardio-neuromodulation, cardio-neuroablation, ARGP

Outcome Measures

Primary Outcome Measures :

1. freedom from syncope [ Time Frame: 12 months ]
2. freedom from serious adverse event [ Time Frame: 7 days ]

Secondary Outcome Measures :

1. freedom from pre syncope [ Time Frame: 12 months ]

Other Outcome Measures:

1. quantification of the vagolysis of the sinus node [ Time Frame: procedure, 1,3,6,12 months ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	14 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Contacts

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Contact: Philippe Debruyne, MD	0032478229896	philippe.debruyne@skynet.be
Contact: Margareta Badts, study nurse	003215514114	Margareta.Badts@imelda.be

Locations

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Belgium
Imeldaziekenhuis	Recruiting
Bonheiden, Antwerpen, Belgium, 2820
Contact: Margareta Badts, study nurse 003215504714 Margareta.Badts@imelda.be
Contact: Philippe Debruyne, MD philippe.debruyne@skynet.be
Principal Investigator: Philippe Debruyne, MD

Sponsors and Collaborators

Imelda Hospital, Bonheiden

Investigators

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Principal Investigator:	Philippe Debruyne, MD	Imeldahospital

More Information

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.

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Responsible Party:	Philippe Debruyne, Principal investigator (PI), Head of Electrophysiology, Imelda Hospital, Bonheiden
ClinicalTrials.gov Identifier:	NCT02954666 History of Changes
Other Study ID Numbers:	B689201629811
First Posted:	November 3, 2016
Last Update Posted:	January 4, 2017
Last Verified:	December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Philippe Debruyne, Imelda Hospital, Bonheiden:

cardio-neuromodulation; cardio-neuroablation; ablation	ganglionated plexi; anterior right ganglionated plexus; syncope

Additional relevant MeSH terms:

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Syncope; Heart Diseases; Sick Sinus Syndrome; Syncope, Vasovagal; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms	Cardiovascular Diseases; Arrhythmia, Sinus; Arrhythmias, Cardiac; Heart Block; Cardiac Conduction System Disease; Pathologic Processes; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases