Study to Compare (COPD) Assessment Test in COPD Stage III and IV in a Prophylactic Treatment

Study Overview
=================
Brief Summary
-----------------
The study will assess the treatment of patients with Chronic Obstructive Pulmonary Disease (COPD) stage III and IV who will self administer the AlphaCore stimulation three times a day over a course of 2 months. Patients will either receive an active AlphaCore device or a Sham device during these two months while not knowing which device they have been provided. At the end of the two months, all patients will be asked to continue in the study for another 2 months to self administer with the active AlphaCore device. Subjects will complete diaries at home on their breathing and quality of life and will return to the clinic monthly for assessment by the investigator.

Detailed Description
-----------------
PERFORMANCE AND SAFETY VARIABLES: The primary efficacy endpoint for this study is the total Chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) score change from baseline to the 8 week follow-up period comparing the two device groups. Secondary efficacy endpoints will be the mean difference from baseline to the 8 week follow-up for the following assessments: Medical Research Council (MRC) dyspnoea scale, 6 minutes walking test and Forced Expiratory Volume in one second (FEV1) Safety Variables: Each subject will be assessed throughout the study for Adverse Events and at the last visit (4 months) subjects will undergo another physical examination including vital signs and blood pressure.

Official Title
-----------------
A Prospective, Single Site, Randomized, Controlled, Parallel Group Study in Subjects With Chronic Obstructive Pulmonary Disease (COPD) Stage III and IV Using AlphaCore or Sham (Control, Not Active) as a Prophylactic Treatment

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Device: AlphaCore device


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 40-75 years Diagnosed Chronic obstructive pulmonary disease(COPD) stage III and IV according to Global Initiative for chronic obstructive lung disease (GOLD) guideline Forced expiratory volume in one second (FEV 1) < 50% Forced expiratory volume in one second (FEV1/Forced expiratory vital capacity (FVC) < 70% Signed informed consent form Exclusion Criteria: Participation in other clinical trials (drug or medical device) 30 days prior to start of this study Subject is unable to comply with the procedures if the protocol for the study or any other reason judged by the Investigator that could interfere with the study assessment or follow-up Has an abscess or other infection or lesion (including lymphadenopathy) at the AlphaCore® treatment site. Is currently implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker, defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant. Has a history of carotid endarterectomy or vascular neck surgery on the right side. Right side or bilateral vagotomy Has a recent or repeated history of syncope. Has a recent or repeated history of seizures. Pregnant or breast feeding women

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active AlphaCore device<br>AlphaCore active stimulation treatment | Device: AlphaCore device<br>* Each study group will go under the same treatment regimen and assessments.<br>|
| Sham Comparator: Sham AlphaCore device<br>AlphaCore sham device | Device: AlphaCore device<br>* Each study group will go under the same treatment regimen and assessments.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Obstructive Pulmonary Disease Assessment Test (CAT) Scores (Quality of Life and Symptoms) Changes Within a Treatment Period and Comparison Between the Two Groups | Chronic obstructive pulmonary disease Assessment Test (CAT) scores (Quality of life and symptoms) changes within a treatment period and comparison between the two groups. Eight (8) questions. The scale is rated from 0 to 5, min = 0, max = 5. Low rates = better, high rates = worse. Mean change in the period 8 weeks versus baseline. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Borg Dyspnoea Scores | Borg dyspnoea scale (Physical activity test): 0 - 11 (Not at all effected - Extremely effected) The result show the change between the the treatment groups from baseline to week 8 | Baseline vs 8 weeks | 
| Change 6 Minutes Walking Test | Six minutes walking test: Measure distance (meter) after 6 minutes walk. Change from Baseline between treatment groups | Baseline vs 8 weeks | 
| Change in Forced Expiratory Volume (FEV1) | Forced Expiratory Volume (FEV1): Maximum volume that can be exhaled in the first second - after maximum inhalation. Change from baseline to week 8 between treatment groups | Baseline vs 8 weeks | 
| Change in EuroQol, 5 Questions and 3 Levels (EQ5D-3L) | The EQ-5D-3L (EuroQoL 5 questions and 3 answering levels) during the run-in period will be compared with the EQ-5D-3L during the treatment period. And treatment period will be compared to open label. Rating of questions Level 1 no problems Level 2 some problems Level 3 Significant problems Worst case is 15 points and best case is 5 points using index | Baseline vs 8 weeks | 
| Number of Subjects With Adverse Events (AE) | All AEs including but not limited to events reported by the subject or reported in response to an open question by the Clinical Investigator or member of this team, which fall into any of the above definitions must be recorded as an AE in the Case Report Form (CRF) and should include the following information. Brief description of the event (diagnosis) Start date (and time, if relevant) Stop date (and time, if relevant) (or resolution) Severity Action taken regarding the medical device Opinion on causality Seriousness Outcome | Throughout the course of the study (baseline to the 4 month follow-up visit) | 
| Change in Change in EuroQol, 5 Questions and 3 Levels (EQ-5D-3L), Visual Analogue Scale (VAS) | Visual analogue scale (VAS) 0-100 where 0 is the worst imaginable health state and 100 the best imaginable health state | Baseline vs 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, vagus nerve stimulation, vagal nerve stimulation, nVNS, VNS, non invasive, gammacore