Evaluate the safety and technical feasibility of TLD Therapy in the treatment of patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).
ID
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Safety Endpoint: Freedom from documented and sustained worsening of
COPD directly attributable to the investigational device or procedure to
180-days post TLD Therapy.
Secondary outcome
Technical Feasibility (performance) Endpoint: The ability of the IPS System to
access the target treatment area and deliver RF energy to the target treatment
site as confirmed by the IPS Console.
Background summary
It is well known that increased smooth muscle tone in patients with Chronic
Obstructive Pulmonary Disease (COPD) is due in part to increased
parasympathetic drive. Pharmacologic blockade of vagus nerve input to airway
smooth muscle in the human lung leads to improvements in lung function and
overall health status. Once daily-inhaled tiotropium improves peak flow by 25%
and causes a 9% sustained improvement
in the forced expiratory volume in one second (FEV1) in patients with COPD with
a baseline FEV1 <= 65% of predicted. It is also known that mechanical disruption
of the vagus nerve as it passes between the brain and the lung can also lead to
improvements in pulmonary function. Intrathoracic bi-lateral vagotomy was
investigated as a treatment for COPD and asthma as early as the 1940s, and most
recently in the 1980s. In patients with severe COPD, surgical resection of the
vagus nerve led to a 30% improvement in FEV1 in one patient with severe COPD.
In severe asthma, vital capacity (VC) has also been shown to improve from 2.36
L to 2.79 L (18%) and maximal voluntary ventilation (a parameter linearly
related to FEV1) increased from 43 L/min to 50 L/min (16%). Prior to vagotomy,
histamine caused a 25% reduction in VC compared to only 9% after vagotomy.
Sputum production was essentially stopped in 8/11 patients with heavy sputum.
However, due to a high risk of procedure related mortality (as high as 28%)
following bilateral thoracotomies, surgical resection of the vagus nerve in the
lung has never been routinely practiced. More recently, knowledge of the
long-term effects of lung denervation has been demonstrated in two patient
populations: 1) lung transplant patients; and, 2) patients who received sleeve
resections (removal of the mainstem bronchus and associated airway nerve
trunks) as treatments for lung cancer. Lung transplant recipients have both
vagus nerve fibers and bronchial arteries severed during surgery. In the early
days of lung transplantation, there was a concern that lung denervation would
lead to worsened physiologic function (i.e. decrease of Hering-Breuer reflex,
decrease of cough reflex). These issues have not been observed did not come to
bear, and lung transplant patients have not been found to have to have any
clinical issues due to their lung denervation. In lung cancer patients, it has
been shown that there is no difference in outcomes, stage by stage, for
patients who received a sleeve resection versus a traditional pneumonectomy for
treatment. It is generally believed that airway nerve trunk branches of the
vagus nerves that influence airway smooth muscle constriction do not re-grow
following transplantation, though there is some evidence that afferent sensory
pathways may regenerate over time. We hypothesize that Targeted Lung
Denervation Therapy will be a safe method to ablate the nerve trunks that
travel parallel to and outside of the main bronchi and into the lungs to
achieve Targeted Lung Denervation.
Study objective
Evaluate the safety and technical feasibility of TLD Therapy in the treatment
of patients with moderate to severe Chronic Obstructive Pulmonary Disease
(COPD).
Study design
This study is prospective, multi-center (3 centers), single-arm
(non-randomized) safety and technical feasibility study.
Intervention
Bronchoscopically guided Targeted Lung Denervation (TLD) Therapy with the
Innovative Pulmonary Solutions (IPS) System.
Study burden and risks
Risks associated with the IPS System are minimized by design. Risks are
minimized under this protocol due to:
- Operators with a high degree of experience in interventional bronchoscopy
- Extensive non-clinical evaluation of the device and therapy (animal and bench
top testing)
- The use of standard medical grade materials in the manufacture of the device
- The well-established nature of the bronchoscopic procedure and technique used
to perform this procedure
- Use of RF energy which is well understood in medical applications
Based upon literature review and pre-clinical evaluations performed to date, it
is expected that TLD therapy may provide some benefit to the subject; however,
this procedure has not been performed in human subjects and the actual benefits
are not known. There may be no direct benefits of study participation.
However, subject participants will undergo an enhanced level of clinical
scrutiny of pulmonary health compared to routine clinical care, which may
provide some indirect health benefits.
A more comprehensive Risk-Benefit assessment is included in the Investigator*s
Brochure provided as Appendix A.
3750 Annapolis Lane North ; Suite 105
Plymouth MN 55447
US
3750 Annapolis Lane North ; Suite 105
Plymouth MN 55447
US
Listed location countries
Age
Inclusion criteria
FEV1 30% - 60% of predicted
FEV1/FVC <70%
Positive change in FEV1 of greater than 15% following administration of ipratropium
Non-smoking for a minimum of 6 months and a minimum of 10 packyears of smoking
Exclusion criteria
Asthma
Prior lung transplant, LVRS, median sternotomy, bullectomy or lobectomy
Presence of a pacemaker, internal defibrillator or other implantable electronic devices
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL36608.042.11 |