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Evaluating the Safety and Feasibility of TLD for the Treatment of Severe Asthma (RELIEF-1)

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ClinicalTrials.gov Identifier: NCT02872298
Recruitment Status : Recruiting
First Posted : August 19, 2016
Last Update Posted : August 7, 2018
Sponsor:
Information provided by (Responsible Party):
Nuvaira, Inc.

Brief Summary:
Prospective, multicenter, single-arm (non-randomized) study of Targeted Lung Denervation (TLD) Therapy in subjects with severe asthma.

Condition or disease Intervention/treatment Phase
Asthma Device: Targeted Lung Denervation (TLD) Not Applicable

Detailed Description:
Prospective, multicenter, single-arm (non-randomized) study. All patients will undergo a run in period on optimal medical therapy as part of eligibility testing. Final determination to initiate treatment will be made after initial airway inspection. A total of 20 patients will be treated. Inflammatory biomarkers (washes and brushes) will be collected in all patients and bronchial biopsies will be collected from the last 10 patients at the time of treatment and at 90-days post-treatment. All patients will be prescribed peri-procedural antibiotics and steroids to minimize procedural risks. All patients will be provided a mobile handheld spirometer to measure and record daily peak expiratory flow both before and after treatment to monitor lung function. Patient follow-up will be conducted out to 3 years.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A pRospective, Multicenter, Single-arm Study EvaLuating the Safety and feasIbility of Targeted Lung Denervation (TLD) for the trEatment oF Severe Asthma
Actual Study Start Date : December 22, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arm Intervention/treatment
Experimental: Treatment
Treatment: Targeted Lung Denervation (TLD)
Device: Targeted Lung Denervation (TLD)
The Nuvaira Lung Denervation System, manufactured by Nuvaira, Inc., is intended to deliver TLD Therapy using predetermined radiofrequency (RF) energy over a predetermined period of time to ablate airway nerve trunks which are located on the outside of the main bronchi.




Primary Outcome Measures :
  1. Freedom from device related therapeutic interventions [ Time Frame: 7 days, 1 month, 3 months, 6 months, and 12 months post-procedure ]
    Number and % of patients free from device related therapeutic interventions will be reported. Therapeutic intervention is defined as administration of non-protocol required antibiotics or steroids, an endoscopic procedure or surgery to treat findings and/or conduction of another diagnostic test to assess the treatment area due to safety concerns.


Secondary Outcome Measures :
  1. Device Success [ Time Frame: 1 day ]
    Number and % of subjects with reported Device Success, defined as the ability to insert and place the dNerva Catheter to its intended locations and intact removal.

  2. Technical Success [ Time Frame: 1 day ]
    Number and % of subjects with reported Technical Success, defined as device success with the ability to deliver RF energy to each intended location as confirmed by the Nuvaira Console.

  3. Change in Quality of Life (QOL) [ Time Frame: Through study completion, an average of 3 years ]
    Changes in the Asthma Quality of Life Questionnaire (AQLQ) over time will be assessed. Comparisons will be made to baseline score.

  4. Change in Asthma Control [ Time Frame: Through study completion, an average of 3 years ]
    Changes in the Asthma Control Questionnaire (ACQ) over time will be assessed. Comparisons will be made to baseline score.


Other Outcome Measures:
  1. Rate of respiratory and non-respiratory adverse events [ Time Frame: Through study completion, an average of 3 years ]
    Rate of respiratory and non-respiratory adverse events

  2. Change in morning and evening peak expiratory flow (PEF) [ Time Frame: Through 1 year follow-up ]
    Change in morning and evening peak expiratory flow (PEF)

  3. Change in pre- and post-bronchodilator FEV1 [ Time Frame: Through study completion, an average of 3 years ]
    Change in pre- and post-bronchodilator FEV1 at pre-specified time points from baseline.

  4. Change in methacholine PC20 [ Time Frame: Through 1 year follow-up ]
    Change in methacholine PC20 (provocation concentration causing a 20% fall in FEV1) at pre-specified time points from baseline.

  5. Change in rescue medication usage [ Time Frame: Through study completion, an average of 3 years ]
    Change in rescue ("reliever") medication usage

  6. Number and level of asthma exacerbations [ Time Frame: Through study completion, an average of 3 years ]
    Number and level of asthma exacerbations

  7. Number of respiratory-related unscheduled physician office visits [ Time Frame: Through study completion, an average of 3 years ]
    Number of respiratory-related unscheduled physician office visits

  8. Number of emergency department visits [ Time Frame: Through study completion, an average of 3 years ]
    Number of emergency department visits

  9. Number of hospitalizations [ Time Frame: Through study completion, an average of 3 years ]
    Number of hospitalizations

  10. Change in inflammatory markers and bronchoscopic specimens [ Time Frame: 90 days ]
    Analysis of inflammatory markers and bronchoscopic specimens collected at treatment and 90 days post-treatment.

  11. Change in visual and quantitative lung attenuation via CT scan [ Time Frame: 1 Year ]
    CT assessment includes visual and quantitative lung attenuation statistics and texture analyses, airway morphometry, regional airflow and airway reactivity, air trapping and structural changes.

  12. Change in Cough [ Time Frame: Through study completion, an average of 3 years ]
    Changes in the Leicester Cough Questionnaire (LCQ) over time will be assessed. Comparisons will be made to baseline score.



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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has provided written informed consent;
  • Diagnosis of severe asthma as defined by the 2018 GINA Report, and are taking regular maintenance medication as specified in the study protocol;
  • Pre-bronchodilator FEV1 ≥50% predicted after a 4 week medication run-in;
  • Subject has at least two days of asthma symptoms during the 4-weeks of the Baseline Diary Period;
  • Women of child bearing potential must have a negative pregnancy test and agree not to become pregnant for the duration during the study;
  • Non-smoker for at least 6 months and agree to continue not smoking for duration of the study;
  • Patient is a candidate for bronchoscopy in the opinion of the physician or per hospital guidelines;
  • Patient is a candidate to undergo methacholine challenge testing;
  • Patient is willing, able and agrees to complete all protocol required baseline and follow up testing and comply with medication requirements.

Exclusion Criteria:

  • In the 24 months prior to enrollment, the subject has: been intubated for asthma, had intensive care unit (ICU) admission(s) for asthma, or been treated with immunosuppressant therapy for any reason (steroids excluded);
  • In the 12 months prior to enrollment, the subject has had: ≥4 lower respiratory tract infections requiring antibiotics or ≥4 hospitalizations for asthma exacerbations;
  • In the 3 months prior to enrollment, the subject has taken/used an opioid(s);
  • In the 6 weeks prior to enrollment the subject has had a lower respiratory tract infection or asthma exacerbation that required: antibiotics, unscheduled physician visits for asthma care, changes in use of asthma maintenance medication, taking of rescue medication over normal dose in a 24-hour period for asthma symptoms and a steroid burst (pulse);
  • Current use of greater than 10 mg of oral steroids per day at the time of enrollment;
  • History of poor medication compliance;
  • Prior lung or chest procedure;
  • Other chronic pulmonary disorders associated with asthma-like symptoms, including (but not limited to) cystic fibrosis, chronic obstructive pulmonary disease, chronic bronchitis, vocal chord dysfunction, eosinophilic granulomatosis with polyangiitis (EGPA) or interstitial lung disease that is the sole cause of asthma symptoms, severe scoliosis or chest wall deformities that affect lung function, or congenital disorders of the lungs or airways;
  • Pre-existing diagnosis of pulmonary hypertension as defined in the study protocol;
  • Uncontrolled diabetes as evidenced by an HbA1c > 7%;
  • Patient has an implantable electronic device;
  • Known contraindication or allergy to anticholinergic drugs or components;
  • Known contraindication of allergy to medications required for bronchoscopy, general anesthesia or peri-procedural therapy that cannot be medically controlled;
  • Patient is unable to stop blood thinning medication for 7 days prior and 7 days after procedure;
  • Documented history of untreated severe obstructive sleep apnea;
  • Patient has any disease or condition that might interfere with completion of a procedure or this study or patient safety;
  • Screening chest CT scan reveals bronchi anatomy cannot be fully treated with the available catheter sizes or discovery of a pulmonary nodule requiring follow-up or intervention unless proven benign;
  • Patients who had abdominal surgical procedures on stomach, esophagus or pancreas;
  • Patients with a Gastroparesis Cardinal Symptom Index (GCSI) score ≥ 18 prior to treatment;
  • Patient is currently enrolled in another clinical trial that has not completed follow-up.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02872298


Contacts
Contact: Delanie Reller 763-450-2800 research@nuvaira.com

Locations
France
CHU de Grenoble Recruiting
Grenoble, France
Contact: Samia Belkacem       sbelkacem@chu-grenoble.fr   
Principal Investigator: Christophe Pison, MD         
Germany
Thoraxklinik Heidelberg Not yet recruiting
Heidelberg, Germany
Contact: Brigitte Rump       brigitte.rump@med.uni-heidelberg.de   
Principal Investigator: Felix Herth, MD         
Netherlands
Academic Medical Center Recruiting
Amsterdam, Netherlands
Contact: Marianne van de Pol       m.a.vandepol@amc.uva.nl   
Principal Investigator: Peter Bonta, MD         
Universtity Medical Center Groningen Recruiting
Groningen, Netherlands
Contact: Jorine Hartman, PhD       j.hartman@umcg.nl   
Principal Investigator: Nick ten Hacken, MD         
United Kingdom
Queen Elizabeth University Hospital Recruiting
Glasgow, Scotland, United Kingdom
Contact: Tracyanne Grandison       Tracyanne.Grandison@ggc.scot.nhs.uk   
Principal Investigator: Stephen Bicknell, MD         
Chelsea & Westminster Hospital NHS Foundation Trust Recruiting
London, United Kingdom
Contact: Karthi Srikanthan       Karthi.Srikanthan@chelwest.nhs.uk   
Principal Investigator: Pallav Shah, MD         
Royal Brompton & Harefield NHS Foundation Trust Not yet recruiting
London, United Kingdom
Contact: Karthi Srikanthan       K.Srikanthan@rbht.nhs.uk   
Principal Investigator: Pallav Shah, MD         
NUH Nottingham City Hospital Not yet recruiting
Nottingham, United Kingdom
Contact: Norma Thompson       Norma.Thompson@nottingham.ac.uk   
Principal Investigator: Dominic Shaw, MD         
University Hospital Southampton NHS Foundation Trust Not yet recruiting
Southampton, United Kingdom
Contact: Yvette Thirlwall       Yvette.Thirlwall@uhs.nhs.uk   
Principal Investigator: Paddy Dennison, MD         
Sponsors and Collaborators
Nuvaira, Inc.
Investigators
Principal Investigator: Nick ten Hacken, MD University Medical Center Groningen (UMCG)
Principal Investigator: Pallav Shah, MD Royal Brompton & Harefield NHS Foundation Trust

Responsible Party: Nuvaira, Inc.
ClinicalTrials.gov Identifier: NCT02872298     History of Changes
Other Study ID Numbers: D0384
First Posted: August 19, 2016    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nuvaira, Inc.:
Severe
Refractory

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases