Fenzian Asthma Multicenter Outcomes Study

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of Fenzian™ treatment on symptoms (such as shortness of breath), lung function (how well the lungs work), and albuterol/salbutamol (rescue medication) use in people with asthma. This will be done by comparing the effects of Fenzian™ treatment to the effects of a sham treatment, which looks the same as the Fenzian™ device but doesn't do anything. The Fenzian™ device is an electrical instrument that the investigators hope will help reduce airway inflammation associated with asthma symptoms by stimulating the nerves with very low electrical currents. The study device will be applied directly to the skin on the back, working along the ribs toward the spine, alternating between left and right sides, and on your face.

Official Title
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Effect of Fenzian™ Treatment on Symptoms, Pulmonary Function and Albuterol/Salbutamol Use in Patients With Mild to Moderate Persistent Asthma: A Multicenter, Sham-Controlled Clinical Trial

Conditions
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Asthma

Intervention / Treatment
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* Device: Fenzian Device
* Device: Sham Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages 12-80 years. [NOTE: Only the Johns Hopkins site will enroll subjects under 18.] Clinical history consistent with asthma (GINA 4 definitions) for at least six months Current symptoms and features of partly-controlled or uncontrolled asthma, according to GINA classification of asthma control A stable (1 month) treatment regimen consisting of: as needed short-acting bronchodilators alone, as needed short-acting bronchodilators in combination with low- or medium-dose inhaled corticosteroids (<= 1000 mcg per day beclomethasone or equivalent, any combination of long acting beta-agonist bronchodilator and low- or medium-dose inhaled corticosteroid (as defined above),as needed short-acting bronchodilators in combination with montelukast or other leukotriene modifier Willingness to comply with the study protocol and ability to perform the study procedures. Willingness to attend the study site according to the specified treatment schedule Inclusion Criteria Assessed at Visit 1: Pre-bronchodilator forced expiratory volume at one second (FEV1) between 60% predicted and the lower limit of normal. Pre-bronchodilator [FEV1/forced vital capacity (FVC)] less than the lower limit of normal. Reversibility of FEV1 of at least 200 ml, 15-20 minutes after 4 puffs of albuterol HFA pressurized metered-dose inhaler pMDI. Inclusion Criteria Assessed at Visit 2: Reversibility of FEV1 of at least 200ml, 15-30 minutes after 4 puffs of albuterol HFA pressurized metered-dose inhaler (pMDI) if not confirmed at Visit 1 plus Using short-acting bronchodilator therapy on two or more occasions in each of the two weeks preceding Visit 2 plus (Ventolin HFA counter decrease of at least 8 puffs) Partly controlled or uncontrolled of asthma as indicated by one to three, but not four of the following in each of the two weeks preceding Visit 2: Daytime symptoms more than twice per week Any limitation of activity Any nocturnal symptoms or awakening peak expiratory flow (PEF)<80% of predicted on any day Exclusion Criteria: Pulmonary disease other than asthma, such as smoking-related chronic obstructive pulmonary disease (COPD), clinically significant bronchiectasis, lung resection, and interstitial lung disease. Other significant systemic illness which might, in the opinion of the investigator alter the risk or outcome of the study (e.g. cardiovascular arrhythmias or conduction abnormalities, hyperthyroidism, uncontrolled hypertension, cancer) Tobacco smoking greater than 10 pack-year of cumulative exposure or current smoking within 10 years. Respiratory tract infection within 6 weeks of the study. Seasonal allergies causing symptoms within the past 4 weeks. Perennial or out of season allergic rhinitis is acceptable. Nasal corticosteroids and long-acting antihistamines are acceptable. Any investigational drug or treatment within 30 days. Use of cromolyn, nedocromil, theophylline, tiotropium, or oral albuterol within 1 week prior to Visit 1 of the study. Current use of omalizumab or within the last 8 weeks. Subjects on anti-depressant (mono-amine oxidase inhibitors or tricyclic antidepressants) treatment within 8 weeks. Non-potassium sparing diuretics unless in fixed combination with potassium-sparing diuretics within one week. Digoxin, within one week, unless levels have been monitored previously while taking albuterol or long-acting beta2-agonist (LABAs). Presence of an implanted cardiac pacemaker or neurostimulator. A removable transcutaneous nerve stimulator, not used during the treatment sessions is acceptable. Non-selective beta agonists. (acceptable choices include: bisprolol, betaxolol, atenolol, acebutolol and metoprolol) Subjects who are pregnant or breast feeding. Persons employed by or related to those employed by the investigative site (e.g. Pulmonary Division). Prior Fenzian treatment for any indication Hypersensitivity or intolerance of albuterol HFA pMDI (Ventolin) or its components. Note: if the subject is using ipratropium bromide for rescue short-acting bronchodilator, they must specifically not have been placed on that treatment due to intolerance of albuterol/salbutamol. Inability to withhold, before and during each visit (except the initial consent visit), xanthine-containing foods (coffee, tea, cola, chocolate, etc.) and alcohol for 6 hours, and short-acting bronchodilators for 8 hours. Unwillingness to stop use of non-study supplied albuterol (nebulized, chlorofluorocarbon (CFC) or HFA), other short-acting beta agonists (e.g. epinephrine, levalbuterol, metaproterenol, pirbuterol, terbutaline) and ipratropium during the study (after consent through visit 4). Inability to coordinate the timing for doses of long-acting beta agonists (withhold period at least 12 hours prior to visit) with Visits 1, 2, 3 or 4

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenzian Device<br>Subjects randomized to this arm will receive treatment with the Fenzian Device | Device: Fenzian Device<br>* Three 20-minute treatments with the Fenzian Device per week for 5 weeks (for a total of 15 treatments)<br>|
| Sham Comparator: Sham Device<br>Subjects randomized to this arm will receive treatment with the sham device. | Device: Sham Device<br>* Three 20-minute treatments with the sham device per week for 5 weeks (for a total of 15 treatments) (NOTE: This arm is similar to a placebo arm in a drug trial.)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Asthma Control Questionnaire (ACQ) 7 Score | Asthma Control Questionnaire (QOL Technologies 2004) Elizabeth Juniper, (Eur Respir J 1999; 14:902-7). Range 0-6, 0 is no symptoms, 6 is maximal symptoms. 0.5 is considered a minimally important difference, 0.75 or less is associated with a 85% chance that the subject's asthma is well controlled, 1.50 or greater is associated with a 88% chance that the subject's asthma is not well controlled. The ACQ consists of 6 patient/subject reported questions on symptoms and a question completed by the staff for categorization of the patient/subjects forced expiratory volume in the first second (FEV1) from spirometry. | Baseline to completion of treatment at 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily Short-acting Bronchodilator (Albuterol/Salbutamol) Use | Daily short-acting bronchodilator use during the 2 weeks, modeled as a zero-modified negative binomial (usually 2 puffs/day) | 2 weeks after completion of treatment (weeks 9-11) | 
| Short-acting Bronchodilator (Albuterol/Salbutamol) Free Days | Percent of rescue-free days during a two week period after completing treatment phase | 2 weeks after completion of treatment (weeks 10 -11) | 
| Change in Asthma Control Questionnaire 6 Score | Asthma Control Questionnaire (QOL Technologies 2004) Elizabeth Juniper, (Eur Respir J 1999; 14:902-7). Range 0-6, 0 is no symptoms, 6 is maximal symptoms. 0.5 is considered a minimally important difference, 0.75 or less is associated with a 85% chance that the subject's asthma is well controlled, 1.50 or greater is associated with a 88% chance that the subject's asthma is not well controlled. The ACQ consists of 6 patient/subject reported questions on symptoms. | Baseline to completion of treatment at 9 weeks | 
| Change in Spirometry - FEV1 |  | Baseline to completion of treatment at 9 weeks | 
| Change in Spirometry - Forced Vital Capacity (FVC) |  | Baseline to completion of treatment at 9 weeks | 
| Change in Spirometry - FEV1/FVC |  | Baseline to completion of treatment at 9 weeks | 
| Change in Spirometry FEF25-75% | A measure of forced expiratory flow between 25% and 75% of FVC (FEF25-75%) | Baseline to completion of treatment at 9 weeks | 
| Change in Asthma Control Test Score | The Asthma Control Test is a 5-item questionnaire using 1-5 point Likert scales; maximum score 25 = complete control of asthma; minimum score 5 = poor control of asthma. | Baseline to completion of treatment at 9 weeks | 
| Change in Mini Asthma Quality of Life Questionnaire (AQLQ) Score (to Evaluate Quality of Life) | The mini AQLQ is a questionnaire specifically designed to assess health status in patients with asthma. The mini-AQLQ consists of 15 questions covering symptoms and activities. Each question is scaled from 1 (poorly controlled asthma) to 7(maximally controlled asthma) where 7 reflects a higher quality of life. Total score is the sum of 15 items and may range from 15-105. An increase in the AQLQ score indicates a better quality of life. | Baseline to completion of treatment at 9 weeks | 
| Change in Sino-Nasal Outcome Test (SNOT-22) - Total Score | The SNOT-22 is a disease-specific quality of life score for rhinosinusitis. SNOT22 is a validated scale which measures sinonasal symptoms for sinusitis patients. The 22 questions are rated on a scale of 0-5 for a maximum total score of 110. Higher scores represent more symptomatic patients. | Baseline to completion of treatment at 9 weeks | 
| Change in SNOT-22 Nasal Sub-score | Sino-nasal outcome test-22 nasal sub-score. The nasal subscore consists of 8 questions, each on a scale of 0 (no problems) to 5 (as bad as it can be). Higher scores indicate worse symptoms of rhinosinusitis. | Baseline to completion of treatment at 9 weeks | 
| Daytime Symptom Score | Daytime symptoms due to asthma were assessed via the electronic diary (AM2+ Asthma Monitor) each evening for 7 days prior to the study visit at Week 15. Daily scores were derived from five questions relating to 1) frequency of asthma symptoms, 2) impact of asthma symptoms, 3) activity, 4) impact of asthma on activity, and 5) breathlessness. Each question was scored from 0 (best) to 6 (worst), with the average of 5 questions providing a daily score ranging from 0 (best) to 6 (worst). Each participant's symptom score was calculated as the average of 7 daily scores. Thus, the range of possible scores is from 0 (best) to 6 (worst). | 7 days prior to final assessment visit at week 15 | 
| Change in Transition Dyspnea Index (TDI) - Functional Impairment | The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI category scores range from -3 (major deterioration) to +3 (major improvement) | Baseline to completion of treatment at 9 weeks | 
| Change in Transition Dyspnea Index - Magnitude of Task at Visit 3 | The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI category scores range from -3 (major deterioration) to +3 (major improvement) | Baseline to completion of treatment at 9 weeks | 
| Change in Transition Dyspnea Index - Magnitude of Effort at Visit 3 | The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI category scores range from -3 (major deterioration) to +3 (major improvement) | Baseline to completion of treatment at 9 weeks | 
| Change in Transition Dyspnea Index - Functional Impairment | The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI category scores range from -3 (major deterioration) to +3 (major improvement) | Baseline to final assessment visit (15 weeks) | 
| Change in Transition Dyspnea Index - Magnitude of Task | The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI category scores range from -3 (major deterioration) to +3 (major improvement) | Baseline to final assessment visit (15 weeks) | 
| Change in Transition Dyspnea Index - Magnitude of Effort | The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI category scores range from -3 (major deterioration) to +3 (major improvement) | Baseline to final assessment visit (15 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Lung Diseases, Respiratory Tract Diseases