Clearance in Primary Ciliary Dyskinesia (CLIP)
Evaluating Non-ciliary Mechanisms of Airway Clearance in Muco-obstructive Lung Disease
Understanding mechanisms of mucus clearance from the airways may lead to treatments in muco-obstructive lung conditions. Mucociliary clearance (MCC) scans are a way to measure the rate at which a person's lungs can clear inhaled particles. Through a single-arm pilot study in participants with primary ciliary dyskinesia (PCD), the investigators will evaluate the effect of exercise as a way to increase clearance through a mechanism called gas liquid transport (GLT) where the faster flow of air through the lungs during exercise is able to clear more particles. The investigators will repeat MCC measures with exercise after administering hypertonic saline (HS) to evaluate the effects of mucus hydration on both GLT and cough clearance (CC).
Aim 1. To quantify non-ciliary, non-cough mechanisms of mucus clearance (i.e., GLT) in PCD through an MCC protocol that introduces a standardized exercise intervention after isotope delivery.
Aim 2. To evaluate whether exercise-induced GLT and/or CC are responsive to hydrator intervention, using a short acting bronchodilator with 7% HS prior to isotope delivery followed by MCC with exercise intervention.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
The investigators will perform an open label, single-arm interventional pilot study with all participants undergoing the interventions (exercise, and exercise with HS pretreatment) and serving as their own control to evaluate the effects of exercise on non-ciliary mucus clearance mechanisms in PCD to better identify role of GLT and CC. The investigators will also evaluate the effect of pretreatment with HS on GLT (if present) and CC, to determine if these mechanisms of mucus clearance are modifiable by future therapies in PCD and other muco-obstructive lung diseases.
Patients will be asked to attend a total of 3 study visits: screening visit 1 (V1), baseline exercise MCC (visit 2 (V2) or visit 3 (V3)), and HS pretreatment MCC (V2 or V3). Patients will be randomized to perform their baseline exercise MCC scan first or their HS pretreatment MCC scan first to minimize introduction of bias. The time between V1 and V2 will be 3 days to 28 days to allow for flexibility of scheduling, but participants already prescribed HS will be required to undergo a washout period of at least 3 days. V3 will take place at least 3 days after V2 to allow for remaining MCC isotope washout. At V1, tolerability and change in airway caliber in response to HS will be assessed by symptom assessment and spirometry, along with the performance of an exercise assessment to inform the exercise protocol in V2 and V3. From the baseline exercise MCC visit, the primary outcome of Whole Lung Total GLT will be measured. Through comparing the data from the exercise MCC visit and the HS pretreatment MCC visit, change in Whole Lung Total GLT and CC will be determined.
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- Nem alkalmazható
Kapcsolatok és helyek
Tanulmányi kapcsolat
- Név: Katherine A Despotes, MD
- Telefonszám: 919-966-1055
- E-mail: katherine.despotes@unchealth.unc.edu
Tanulmányozza a kapcsolattartók biztonsági mentését
- Név: Corinne Taylor
- E-mail: corinne.lawler@unc.edu
Tanulmányi helyek
-
-
North Carolina
-
Chapel Hill, North Carolina, Egyesült Államok, 27278
- University of North Carolina at Chapel Hill
-
Kapcsolatba lépni:
- Katherine A Despotes, MD
- Telefonszám: 919-966-1055
- E-mail: katherine.despotes@unchealth.unc.edu
-
Kapcsolatba lépni:
- Corinne Taylor
- E-mail: corinne.lawler@unc.edu
-
Kutatásvezető:
- Katherine A Despotes, MD
-
-
Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
- Felnőtt
- Idősebb felnőtt
Egészséges önkénteseket fogad
Leírás
Inclusion Criteria:
- 18 years old or older
- Diagnosis of PCD with supporting genetics
- Lung function with forced expiratory volume in 1 second (FEV1) percent predicted >30%
- Ability to exercise for 20 minutes (Exercise Assessment performed at screening visit)
Exclusion Criteria:
- Intolerance to 7% HS
- Failure of HS tolerance test (HSTT) at visit 1 (V1), defined as a decline of 10% in FEV1 from baseline pre-bronchodilator (BD) FEV1 after 7% HS
- Intolerance to levalbuterol
- Exercise-induced asthma
- Complex congenital heart disease or other exercise limitation
- Lung transplantation or listed for lung transplantation
- History of lung resection of the lung analyzed by MCC (depending on situs status)
- Pregnancy or unwillingness to use approved birth control during study period
- Recent hemoptysis (>60 ml in the last 3 months)
- Pulmonary exacerbation in preceding 4 weeks
- Change in pulmonary therapies within preceding 4 weeks
- Resting or exertional O2 requirement (nocturnal acceptable)
- Tobacco / smoking history (any within last year, and >10 pack year history in past)
- More than 2 chest computed tomography (CT) scans in the past year or a combination of procedures believed to have exposed the lungs to >150 millisieverts (mSv), including from other research studies
- Participation in another interventional trial within 30 days
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: N/A
- Beavatkozó modell: Egyetlen csoportos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
|
Kísérleti: Exercise with and without HS pretreatment
All participants will undergo interventions of exercise alone, and exercise with HS pretreatment, in two separate study visits according to randomization to intervention sequence.
|
At either V2 or V3, after 16 minutes of baseline MCC data collection, participants will perform 20 minutes of moderate-intensity exercise based on the Borg Rating of Perceived Exertion (RPE) scale, on a cycle ergometer.
The goal through this moderate intensity exercise is to increase respiratory rate and airflow velocity, thereby potentially inducing GLT.
Participants will then resume MCC scan data collection post-exercise to continue to measure the effects induced by exercise on clearance from the lungs.
At either V2 or V3, prior to the start of baseline MCC scanning, participants will undergo pretreatment with 4 puffs of inhaled levalbuterol (90 mcg per actuation, via spacer) followed by 4 ml of 7% HS via nebulizer.
Participants will then start MCC scan data collection, and after 16 minutes of baseline MCC collection they will then complete 20 minutes of moderate intensity exercise according to the Borg RPE on a cycle ergometer.
After 20 minutes, MCC scan will resume to continue to measure rates of clearance following HS pretreatment and exercise.
|
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Whole Lung Total GLT
Időkeret: Either Day 1 (Visit 2) or up to Day 28 (Visit 3) depending on randomization to sequence intervention
|
Through MCC scan with built in exercise protocol, the investigators will measure the effects of exercise on rates of clearance of radiolabeled isotopes from the lungs, thought to represent GLT.
The investigators will measure the difference between retained particles from immediately before (after collection of 16 minutes of baseline MCC data through eight 2-minute images) and immediately after 20 minutes of moderate intensity exercise on a cycle ergometer (40 minutes after start of MCC data collection).
This will represent Active GLT.
The investigators will then resume measurement of MCC clearance rate by serial 2-minute image collection of the whole lung from 40 minutes to 70 minutes.
This will represent Sustained GLT.
The sum of Active and Sustained GLT will represent Whole Lung GLT.
This measurement will occur at either Visit 2 or Visit 3, depending on visit sequence randomization.
|
Either Day 1 (Visit 2) or up to Day 28 (Visit 3) depending on randomization to sequence intervention
|
|
Change in Whole Lung Total GLT after HS pretreatment
Időkeret: Day 3 to 28, depending on timing of Visit 3
|
After pretreatment with levalbuterol and 7% HS, participants will undergo an MCC scan with built in exercise protocol.
The investigators will measure the effects of exercise on rates of clearance of radiolabeled isotopes from the lungs, thought to represent GLT.
The investigators will measure Active GLT and Sustained GLT after HS pretreatment, which taken together will represent Whole Lung GLT after HS pretreatment.
This measurement will occur at either Visit 2 or Visit 3 depending on visit sequence randomization.
The difference between Whole Lung GLT from exercise alone will be compared with the HS pretreatment Whole Lung GLT.
|
Day 3 to 28, depending on timing of Visit 3
|
|
Change in Cough Clearance (CC) after HS Pretreatment
Időkeret: Day 3 to 28, depending on timing of Visit 3
|
The investigators will measure the effects of exercise and HS pretreatment on rates of clearance of radiolabeled isotopes from the lungs during a period of controlled coughs at regular intervals.
During Visit 2 and Visit 3 MCC scans, from minutes 70 through 100 of MCC data collection, participants will be instructed to perform 30 voluntary huff-cough maneuvers while serial 2-minute images are obtained.
The change in clearance during this time will represent CC.
At one of these visits (either Visit 2 or Visit 3 depending on randomization to intervention sequence), participants will undergo pretreatment with levalbuterol and 7% HS prior to the MCC scan with exercise protocol.
The difference between CC after exercise alone and CC after exercise with HS pretreatment will be measured.
|
Day 3 to 28, depending on timing of Visit 3
|
Együttműködők és nyomozók
Együttműködők
Nyomozók
- Kutatásvezető: Katherine A Despotes, MD, University of North Carolina, Chapel Hill
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
- Ciliopathiák
- Genetikai betegségek, veleszületett
- Légúti betegségek
- Veleszületett rendellenességek
- Fül-orr-gégészeti betegségek
- Rendellenességek, többszörös
- Veleszületett, örökletes és újszülöttkori betegségek és rendellenességek
- Viselkedés
- Ciliáris motilitási zavarok
- Motoros tevékenység
- Motoros aktivitás
- Mozgás
- Izom -csontrendszeri fiziológiai jelenség
- Izom -csontrendszeri és idegi fiziológiai jelenség
- Gyakorlat
Egyéb vizsgálati azonosító számok
- 25-1650
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
IPD terv leírása
Gyógyszer- és eszközinformációk, tanulmányi dokumentumok
Egy amerikai FDA által szabályozott gyógyszerkészítményt tanulmányoz
Egy amerikai FDA által szabályozott eszközterméket tanulmányoz
az Egyesült Államokban gyártott és onnan exportált termék
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .