NeuRx Diaphram Pacing System (DPS) Use in Amyotrophic Lateral Sclerosis (ALS) (PARADIGM)

Multi-Center, Concurrent-Controlled, On-Label Study of the NeuRx Diaphragm Pacing System (DPS) in Participants With Amyotrophic Lateral Sclerosis (ALS)

The purpose of this research study is to collect more information about the use, safety, and effectiveness of the NeuRx DPS® in ALS patients.

Study Overview

• Status: Withdrawn
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Device: NeuRx DPS

Detailed Description

Characterize the safety and benefit of on-label Humanitarian Device Exemption (HDE) use of DPS in patients with ALS who initiated noninvasive ventilation (NIV).

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 21 or older
• Familial or sporadic ALS diagnosed as possible, laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria
• Bilateral phrenic nerve function clinically acceptable as demonstrated by bilateral diaphragm movement with fluoroscopic sniff test or with phrenic nerve conduction studies

• Chronic hypoventilation was documented by at least one of the following:

  • MIP (respiratory muscle strength) less than 60 cmH2O, or
  • Forced Vital Capacity (FVC) less than 50% predicted, or
  • PaCO2 greater than or equal to 45 mmHg, or
  • Nocturnal SaO2 (arterial oxygen saturation) less than or equal to 88% for at least five continuous minutes
• Initiation of non-invasive ventilation at or before time of enrollment
• Suitable surgical candidate to receive diaphragm pacing stimulation
• Negative pregnancy test in female participants of childbearing potential (treatment group)
• Informed consent from patient or designated representative

Exclusion Criteria:

• FVC less than 45% predicted within 10 days prior to surgery.
• Participation in simultaneous therapeutic clinical trial which could affect the safety or benefit outcomes of this study.

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
Active Comparator: NeuRx DPS; Subjects who have initiated noninvasive ventilation (NIV) and receive the NeuRx diaphragm pacing system (DPS).	Device: NeuRx DPS; Patients who are diagnosed with ALS, have initiated NIV and choose to have the NeuRx DPS implanted.; Other Names: Diaphragm Pacing System
No Intervention: No DPS; Subjects who have initiated noninvasive ventilation (NIV) and do not receive the DPS device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Compare the survival of patients who initiated noninvasive ventilation (NIV).and who receive DPS to controls without DPS: (1) concurrent controls; (2) historical controls (e.g., Lechtzin and PRO-ACT databases); and (3) virtual controls (Origent).	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between survival time and clinical features of ALS	Determine whether there is a relationship between survival time and ALS onset type.	24 months
Relationship between survival time and ALS assessment scores	Determine whether there is a relationship between survival time and Upper Motor Neuron (UMN)/ Lower Motor Neuron (LMN) assessment scores.	24 months
Relationship between survival time and onset of weakness from ALS to treatment		24 months
Relationship between survival time and ALS treatment interventions		24 months
Relationship between survival time and intraoperative strength of contraction		24 months
Characterize change in overall and respiratory function	Characterize longitudinal change in overall function (ALSFRS-R) before and after treatment with DPS compared to controls.	24 months
Characterize change in respiratory function	Characterize longitudinal change in respiratory function (FVC, MIP) before and after treatment with DPS compared to controls.	24 months
Types device and procedure-related adverse events		24 months
Frequency of device and procedure-related adverse events		24 months
Types of respiratory serious adverse events		24 months
Frequency of respiratory adverse events		24 months

Collaborators and Investigators

• Sponsor: Synapse Biomedical
• Investigators: Principal Investigator: Robert Miller, MD, California Pacific Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): February 8, 2018
• Study Completion (Actual): February 12, 2018

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (Estimate): January 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Diaphragm Pacing
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 20-1000-51

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes