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.
研究概览
详细说明
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.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Katherine A Despotes, MD
- 电话号码：919-966-1055
- 邮箱：katherine.despotes@unchealth.unc.edu
研究联系人备份
- 姓名：Corinne Taylor
- 邮箱：corinne.lawler@unc.edu
学习地点
-
-
North Carolina
-
Chapel Hill、North Carolina、美国、27278
- University of North Carolina at Chapel Hill
-
接触：
- Katherine A Despotes, MD
- 电话号码：919-966-1055
- 邮箱：katherine.despotes@unchealth.unc.edu
-
接触：
- Corinne Taylor
- 邮箱：corinne.lawler@unc.edu
-
首席研究员：
- Katherine A Despotes, MD
-
-
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
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
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：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.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Whole Lung Total GLT
大体时间：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
大体时间：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
大体时间：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
|
合作者和调查者
调查人员
- 首席研究员：Katherine A Despotes, MD、University of North Carolina, Chapel Hill
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 25-1650
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
在美国制造并从美国出口的产品
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.