Feasibility Study to Determine the Effects of Phrenic Nerve Stimulation in Patients With Periodic Breathing

The purpose of this feasibility study is to determine the effect of stimulating the phrenic nerve to treat periodic breathing (a pattern of breathing characterized by hyperpneas followed by hypopneas or apneas). Clinically, these physiologic events translate into sleep fragmentation, excessive daytime sleepiness, reduced exercise capacity, and possibly ventricular arrhythmias.

Stage 1 of the study is acute in nature, such that subjects will undergo the placement of a stimulation lead, followed by assessment of stimulation of the phrenic nerve using the lead for up to 2 nights of sleep. A sensing lead may also be placed during the initial implant procedure. Observational data will be obtained and stimulation provided using an externalized system connected to the study leads. Following the study, all investigational components will be removed from the patient.

Stage 2 of the study is being conducted at one of the participating sites to determine the initial safety of chronic stimulation of the phrenic nerve in a limited number of patients with sleep disordered breathing. It is anticipated that data obtained in this feasibility study will show that the proposed intervention can modify respiration with a low incidence of adverse effects. The results of this trial are intended to be used to develop a subsequent protocol for a multi-center study of chronic phrenic nerve pacing.

Study Overview

• Status: Completed
• Conditions: Cheyne-Stokes Respiration; Sleep Apnea; Sleep Disordered Breathing
• Intervention / Treatment: Device: Phrenic stimulation device

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Nanjing, China
    • Jiangsu Province Hospital
• Poland
  • Wroclaw, Poland
    • Polish Military Hospital
• United States
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Hennepin County Medical Center
  • Ohio
    • Cincinnati, Ohio, United States
      • Ohio Heart Hospital
    • Columbus, Ohio, United States
      • The Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient is 18 years of age or older
• Patient has a demonstrated history of periodic breathing (symptoms may include sleep fragmentation, as reported by patient or as witnessed by another person, night arousal after apneic episodes, reduced exercise capacity, and daytime sleepiness)
• Patient is expected to be able to tolerate the procedure and remain clinically stable for the duration of the study (e.g. the subject is able to lie down long enough to insert the lead(s) without shortness of breath and the subject is able to tolerate instrumentation during study).
• Patient or their legal representative is willing and able to sign an IRB/MEC approved informed consent (and a privacy protection authorization in the United States)

Exclusion Criteria:

• Baseline oxygen saturation less than or equal to 90% on a stable FIO2
• Evidence of phrenic nerve palsy
• Temperature > 38.0 degrees Celsius
• Inability to place catheter (e.g. previously known coagulopathy, distorted anatomy, etc.)
• Patient is currently enrolled in another study that may confound the results of this study
• Patient for whom informed consent cannot be obtained
• Patient who is pregnant or of child bearing potential without a negative pregnancy test within 10 days of the study procedure
• Patients implanted with a pacemaker, implantable defibrillator, or cardiac resynchronization device who are unable to tolerate turning off the device for the duration of the system testing procedure (based on medical judgment)
• Patients with severe COPD (per GOLD scale)
• Patients with a history of myocardial infarction within 6 months prior to the study
• Patients with unstable angina
• Patients who are intolerant of or allergic to contrast dye
• Patients who are contraindicated for <1mg of steroid (on the stimulation lead).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Phrenic Stimulation

Device: Phrenic stimulation device; In Stage 1, a stimulation lead will be introduced via standard access methods and positioned to provide stimulation. A second lead may also be placed for sensing purposes. The proximal portions of the implanted lead(s) will remain externalized such that stimulation and observation can be made using external stimulation and recording equipment. Study subjects will be observed and stimulation will be performed for up to 2 nights of sleep in a clinically supported environment. In Stage 2, a stimulation device and lead will be permanently implanted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary goal of this feasibility study is to show an acute improvement in respiration.	Acute (up to 2 nights of sleep)
The primary safety endpoint of the study is the absence of adverse events related to stimulation that result in hospitalization, the prolongation of an existing hospitalization, or death of the patient.	Acute (up to 2 nights of sleep) plus post-operative assessment at one week (5-10 days) or until resolution of an observed adverse event.

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterization of chronic safety of stimulating the phrenic nerve (Stage 2 of study).	2 years

Collaborators and Investigators

• Sponsor: Respicardia, Inc.

Publications and helpful links

General Publications

• Zhang XL, Ding N, Wang H, Augostini R, Yang B, Xu D, Ju W, Hou X, Li X, Ni B, Cao K, George I, Wang J, Zhang SJ. Transvenous phrenic nerve stimulation in patients with Cheyne-Stokes respiration and congestive heart failure: a safety and proof-of-concept study. Chest. 2012 Oct;142(4):927-934. doi: 10.1378/chest.11-1899.
• Ponikowski P, Javaheri S, Michalkiewicz D, Bart BA, Czarnecka D, Jastrzebski M, Kusiak A, Augostini R, Jagielski D, Witkowski T, Khayat RN, Oldenburg O, Gutleben KJ, Bitter T, Karim R, Iber C, Hasan A, Hibler K, Germany R, Abraham WT. Transvenous phrenic nerve stimulation for the treatment of central sleep apnoea in heart failure. Eur Heart J. 2012 Apr;33(7):889-94. doi: 10.1093/eurheartj/ehr298. Epub 2011 Aug 19.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: May 21, 2009
• First Submitted That Met QC Criteria: May 22, 2009
• First Posted (Estimate): May 27, 2009

Study Record Updates

• Last Update Posted (Estimate): January 6, 2014
• Last Update Submitted That Met QC Criteria: January 2, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Sleep Apnea; Sleep Disordered Breathing; Cheyne-Stokes Respiration; Periodic Breathing
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Respiratory Aspiration; Cheyne-Stokes Respiration
• Other Study ID Numbers: CCI-Feasibility