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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Katherine A Despotes, MD
- Telefonní číslo: 919-966-1055
- E-mail: katherine.despotes@unchealth.unc.edu
Studijní záloha kontaktů
- Jméno: Corinne Taylor
- E-mail: corinne.lawler@unc.edu
Studijní místa
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North Carolina
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Chapel Hill, North Carolina, Spojené státy, 27278
- University of North Carolina at Chapel Hill
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Kontakt:
- Katherine A Despotes, MD
- Telefonní číslo: 919-966-1055
- E-mail: katherine.despotes@unchealth.unc.edu
-
Kontakt:
- Corinne Taylor
- E-mail: corinne.lawler@unc.edu
-
Vrchní vyšetřovatel:
- Katherine A Despotes, MD
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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.
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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.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Whole Lung Total GLT
Časové okno: Either Day 1 (Visit 2) or up to Day 28 (Visit 3) depending on randomization to sequence intervention
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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.
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Either Day 1 (Visit 2) or up to Day 28 (Visit 3) depending on randomization to sequence intervention
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Change in Whole Lung Total GLT after HS pretreatment
Časové okno: Day 3 to 28, depending on timing of Visit 3
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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.
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Day 3 to 28, depending on timing of Visit 3
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Change in Cough Clearance (CC) after HS Pretreatment
Časové okno: Day 3 to 28, depending on timing of Visit 3
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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.
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Day 3 to 28, depending on timing of Visit 3
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Spolupracovníci a vyšetřovatelé
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Katherine A Despotes, MD, University of North Carolina, Chapel Hill
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Ciliopatie
- Genetické choroby, vrozené
- Nemoci dýchacích cest
- Vrozené vady
- Otorinolaryngologická onemocnění
- Abnormality, vícenásobné
- Vrozené, dědičné a neonatální nemoci a abnormality
- Chování
- Poruchy ciliární motility
- Motorická aktivita
- Motorická aktivita
- Hnutí
- Muskuloskeletální fyziologické jevy
- Muskuloskeletální a nervové fyziologické jevy
- Cvičení
Další identifikační čísla studie
- 25-1650
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
produkt vyrobený a vyvážený z USA
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