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Novel Therapies for Muco-Obstructive Lung Diseases: Testing the Transnasal Pulmonary Delivery Device in COPD/CB Subjects (tPAD)

Primary Purpose

COPD, Chronic Bronchitis

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

tPAD

7% hypertonic saline (510K approved as a device)

About this trial

This is an interventional other trial for COPD

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects who meet the following criteria will be eligible for study participation:

Subjects aged 40 to 80 years (inclusive), and with a body mass index (BMI) < 35 kg/m2
Female subjects must be non-pregnant and must be either not sexually active, post-menopausal, surgically sterilized, or agree to use an appropriate "double-barrier" method (such as a diaphragm and condom); or, must currently be using a prescribed transdermal, injection, implant, or oral contraceptive during study participation
Subjects who are in their baseline state of health, as determined by a medical history and examination
Subjects who have normal lung function with a FEV1 of 30% - 80% predicted and a FEV1/FVC <70%
Subjects who are capable of providing written informed consent in English to participate in the study
Produces sputum two days per week or more, on average.
History of smoking cigarettes ≥ 10 pack years.

Exclusion Criteria:

Subjects will be excluded from the study according to the following criteria:

Subjects who use oxygen continuously or require it at night.
Subjects with an FEV1 < 30% or > 80% or an FEV1/FVC of ≥70% at screening.
Subjects who chronically require > 10mg per day of prednisone (or equivalent corticosteroid dose).
Subjects with a concomitant presence of congestive heart failure, active coronary syndromes, or other disease that in the opinion of the investigator would increase the risk resulting from participation.
Subjects with a recent change in respiratory medications, including new antibiotic or systemic corticosteroid interventions within the last 4 weeks.
Subjects with a history of intolerance or hypersensitivity to hypertonic saline or short acting inhaled beta agonists.
Subjects with significant bronchoreactivity by examination or PFT testing that, in the opinion of the investigator, would increase the risk of HS use.
Subjects who have had radiation exposure within the 12 months prior to study participation that would cause them to exceed Federal Regulations by participating in this study.
Subjects with symptomatically active, chronic or acute rhinosinusitis, or other nasal abnormality that could interfere with aerosol delivery or impact subject safety.
Subjects with a positive pregnancy test or who are nursing.
Subjects who have been diagnosed with obstructive sleep apnea.
Subjects who, in the opinion of the Principal Investigator, should not participate in the study.
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Sites / Locations

University of North Carolina Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

A: Treatment order: tPAD treatment, then no treatment

B: Treatment order: no treatment, then tPAD treatment

Arm Description

Subjects will receive one overnight treatment with 7% hypertonic saline administered via the tPAD device. They will then have one overnight stay without treatment.

Subjects will have overnight stay w/o treatment, and one overnight treatment with 7% hypertonic saline administered via the tPAD device.

Outcomes

Primary Outcome Measures

Mucociliary Clearance Rate (MCC60)

The primary study outcome, MCC60, will serve as the primary descriptor of the mucociliary clearance rate. This assay will be begun as quickly as possible after competing the tPAD treatment (<60 minutes in all cases). MCC60 is derived by calculating the average rate of particle clearance observed during the first 60 minutes of the MCC scan procedure (MCC60; units = % cleared/time), using clearance values determined every 10 minutes for 60 minutes following inhalation of radiolabeled particles. Results obtained immediately after tPAD treatment will be compared to baseline values. Similarly, average clearance through other time domains (30 min, 90 min, 24 hrs), and from specific regions of interest (central lung; peripheral lung) will be reported as secondary MCC outcomes.

Secondary Outcome Measures

Symptom survey

A customized survey of nasal, sleep, and respiratory symptoms will be administered to qualitatively assess the experience with the tPAD device.

Spirometry

For treatment visits, spirometry will be obtained before treatment and after the overnight treatment following the MCC study to assess safety of the assigned interventions.

Full Information

NCT ID

NCT02341183

First Posted

December 2, 2014

Last Updated

June 22, 2017

Sponsor

University of North Carolina, Chapel Hill

1. Study Identification

Unique Protocol Identification Number

NCT02341183

Brief Title

Novel Therapies for Muco-Obstructive Lung Diseases: Testing the Transnasal Pulmonary Delivery Device in COPD/CB Subjects

Acronym

tPAD

Official Title

Novel Therapies for Muco-Obstructive Lung Diseases: A Study of Tolerability and MCC Effect of Hypertonic Saline Delivered Via the tPAD in Patients With Chronic Bronchitis

Study Type

Interventional

2. Study Status

Record Verification Date

May 2016

Overall Recruitment Status

Withdrawn

Study Start Date

May 2016 (undefined)

Primary Completion Date

May 2016 (Actual)

Study Completion Date

May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of North Carolina, Chapel Hill

4. Oversight

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The primary objective of this study is to assess tolerability and effect of HS (hypertonic saline) delivered with the tPAD (transnasal Pulmonary Aerosol Delivery) device on mucociliary clearance (MCC) in chronic obstructive pulmonary disease/chronic bronchitis (COPD/CB) subjects. The investigators hypothesize that HS delivery via tPAD will be safe and and while, and will improve MCC.

Detailed Description

The beneficial effects of inhaled HS in CF patients (cystic fibrosis) have been well established. Concerns over safety and intolerability in patients with COPD/CB, based in part upon experiences with ultrasonic delivery devices, have limited interest in further exploring this therapeutic option. Although our clinical data suggests that HS delivered via jet nebulizer is generally well tolerated in patients with COPD/CB, our pre-clinical data suggests that cell shrinkage, the release of proinflammatory cytokines (i.e. IL-8), and transient cilia stasis is dependent upon the rate of aerosol delivery. Slow/continuous delivery may avoid most/all of these detrimental effects while promoting an even greater cumulative ASL (airway surface liquid) volume increase. To translate these data into a feasible treatment strategy, a comfortable, quiet delivery device that can be used for long time periods (i.e. overnight) was developed to slowly deliver HS via a nasal cannula device while avoiding aerosol rain-out in the device's tubing. Use of a computational model (MPPD: Multiple-Path Particle Dosimetry V2.0) predicts that this device, which generates a 2 um MMAD aerosol particle, will achieve -5-8% lung deposition. When tuned to an output of ~0.033 ml/min, 8 hours of use is predicted to deposit a minimum of 140 mg of NaCI onto airway surfaces. This compares favorably to the estimated mass delivered via jet nebulizer in the clinically successful study of HS in CF (110 mg/day, assuming 19.75% deposition fraction with the Pari LC PLUS). The proposed study is a single site, randomized, open label, cross-over trial designed to measure the tolerability and effect on mucociliary clearance following 7% HS delivered via tPAD for eight hours overnight to COPD/CB subjects. Comparison will be to measurements made following no treatment during an overnight stay. COPD/CB subjects meeting inclusion and exclusion criteria will be enrolled in the study. All study procedures will be conducted in the Clinical Translational Research Center (CTRC) at UNC Hospitals and the EPA building on Mason Farm Rd on the UNC Hospitals campus.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COPD, Chronic Bronchitis

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A: Treatment order: tPAD treatment, then no treatment

Arm Type

Active Comparator

Arm Description

Subjects will receive one overnight treatment with 7% hypertonic saline administered via the tPAD device. They will then have one overnight stay without treatment.

Arm Title

B: Treatment order: no treatment, then tPAD treatment

Arm Type

Active Comparator

Arm Description

Subjects will have overnight stay w/o treatment, and one overnight treatment with 7% hypertonic saline administered via the tPAD device.

Intervention Type

Device

Intervention Name(s)

tPAD

Intervention Description

7% NaCl administered continuously for 8 hours, overnight, via the tPAD device

Intervention Type

Device

Intervention Name(s)

7% hypertonic saline (510K approved as a device)

Intervention Description

Subjects will receive overnight treatments of 7% HS via the tPAD device in both comparators, but in a randomly assigned order as described.

Primary Outcome Measure Information:

Title

Mucociliary Clearance Rate (MCC60)

Description

Time Frame

The MCC outcome measure will be performed as quickly as possible (within 60 minutes) after overnight tPAD treatment

Secondary Outcome Measure Information:

Title

Symptom survey

Description

A customized survey of nasal, sleep, and respiratory symptoms will be administered to qualitatively assess the experience with the tPAD device.

Time Frame

The outcome measure will be assessed after visits 1 and 3, immediately following each overnight visit (tPAD vs. no treatment)

Title

Spirometry

Description

For treatment visits, spirometry will be obtained before treatment and after the overnight treatment following the MCC study to assess safety of the assigned interventions.

Time Frame

Spirometry will be performed before each treatment visit (tPAD vs. no treatment) on Visit 1 and 3, and again after completing the assigned treatment, approximately 12 hours later

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects who meet the following criteria will be eligible for study participation: Subjects aged 40 to 80 years (inclusive), and with a body mass index (BMI) < 35 kg/m2 Female subjects must be non-pregnant and must be either not sexually active, post-menopausal, surgically sterilized, or agree to use an appropriate "double-barrier" method (such as a diaphragm and condom); or, must currently be using a prescribed transdermal, injection, implant, or oral contraceptive during study participation Subjects who are in their baseline state of health, as determined by a medical history and examination Subjects who have normal lung function with a FEV1 of 30% - 80% predicted and a FEV1/FVC <70% Subjects who are capable of providing written informed consent in English to participate in the study Produces sputum two days per week or more, on average. History of smoking cigarettes ≥ 10 pack years. Exclusion Criteria: Subjects will be excluded from the study according to the following criteria: Subjects who use oxygen continuously or require it at night. Subjects with an FEV1 < 30% or > 80% or an FEV1/FVC of ≥70% at screening. Subjects who chronically require > 10mg per day of prednisone (or equivalent corticosteroid dose). Subjects with a concomitant presence of congestive heart failure, active coronary syndromes, or other disease that in the opinion of the investigator would increase the risk resulting from participation. Subjects with a recent change in respiratory medications, including new antibiotic or systemic corticosteroid interventions within the last 4 weeks. Subjects with a history of intolerance or hypersensitivity to hypertonic saline or short acting inhaled beta agonists. Subjects with significant bronchoreactivity by examination or PFT testing that, in the opinion of the investigator, would increase the risk of HS use. Subjects who have had radiation exposure within the 12 months prior to study participation that would cause them to exceed Federal Regulations by participating in this study. Subjects with symptomatically active, chronic or acute rhinosinusitis, or other nasal abnormality that could interfere with aerosol delivery or impact subject safety. Subjects with a positive pregnancy test or who are nursing. Subjects who have been diagnosed with obstructive sleep apnea. Subjects who, in the opinion of the Principal Investigator, should not participate in the study. -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Scott H. Donaldson, MD

Organizational Affiliation

Associate Professor, Department of Medicine, Division of Pulmonary/Critical Care Medicine, UNC Chapel Hill

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of North Carolina Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Novel Therapies for Muco-Obstructive Lung Diseases: Testing the Transnasal Pulmonary Delivery Device in COPD/CB Subjects

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