Hypertonic Saline in NCFB

Официальное название

Effect of Hypertonic Saline on Mucociliary Clearance in Non-CF Bronchiectasis

Обзор

The purpose of this single arm clinical trial is to evaluate the effects of 7% hypertonic saline (HS) delivered by nebulizer on clearance of mucus from the lungs in people with bronchiectasis (dilated airways) not due to cystic fibrosis. Mucociliary clearance (MCC) to measure the rate at which a person's lungs can clear inhaled particles will be assessed at baseline, and after acute (single dose) HS treatment, as well as after two weeks of treatment with HS. The study has two main questions: 1. Evaluate the repeatability MCC measures in people with non-CF bronchiectasis 2. Compare MCC at baseline (before treatment with HS), after a single dose of HS (acute effect of HS), and after two weeks of treatment with HS twice a day (sustained effect of HS). Participants will participate in up to 5 study visits if completing both Aim 1 and Aim 2: 1 screening/enrollment visit, 2 baseline visits (1 baseline visit if only participating in Aim 2), 1 visit during which first dose of HS would be administered and assessed, and 1 visit after 2 weeks of treatment with HS.

Подробное описание

The investigators will perform an open label, single arm pilot study of 7% HS as our treatment intervention in patients with NCFB. Participants will attend up to 5 study visits.

The first visit (V1) will be a screening visit to obtain informed consent if not already obtained, confirm that subjects meet all eligibility criteria through review of medical history and clinical records, and performance of a hypertonic saline tolerance test (HSTT). Participants meeting eligibility criteria will be enrolled in the study at that time, and subsequent study visits will be scheduled.

At each study visit, medical history will be reviewed. Pregnancy testing will be performed at all visits in participants who may become pregnant. Up to two baseline MCC scans (V2 and optional V3) will be performed under baseline conditions to assess variability, and expectorated sputum will be collected at either visit. Baseline spirometry and MBW will also be obtained at V2 and V3, and QOL-B will be assessed at V2 prior to any other study procedures that could impact their symptoms and responses.

At V4, the acute response to HS on MCC will be assessed after the first dose of HS is administered at the visit, marking the start of the two-week treatment period. Participants will be given a supply of HS to incorporate in their airway clearance regimen twice a day for two weeks (treatment period of up to 17 days, depending on exact timing of when V5 falls).

The evening prior to V5, patients will perform airway clearance and receive their final dose of HS. The following morning, they will hold airway clearance until after their study visit. At V5, they will complete post-treatment QOL-B, and Treatment Satisfaction Questionnaire for Medication (TSQM), MBW, spirometry, MCC (12 hours after last dose of HS, to assess sustained response to HS), and sputum collection.

Вмешательства

• Препарат 7% Hypertonic Saline via nebulization
  Twice a day treatment with nebulized 7% HS for 2 weeks as part of airway clearance

Первичные конечные точки

• Repeatability of Mucociliary Clearance (MCC) at 60 minutes [Срок оценки: Day 1 (Visit 2) up to Day 14 +/- 3 (Visit 3)]
• Average change in MCC60 from baseline (Visit 2 and 3), after acute treatment with HS (Visit 4), and after two weeks of treatment with HS (Visit 5) [Срок оценки: Day 1 (Visit 2) up to 7 weeks (Visit 5)]

Вторичные конечные точки (4)

• Change in Forced Expiratory Volume in 1 Second (FEV1) from Baseline (mean from visit 2 and visit 3, pre-HS treatment) to Visit 5 (post-HS treatment period) [Срок оценки: Day 1 (Visit 2) up to 7 weeks (Visit 5)]
• Change in Quality of life for Bronchiectasis (QOL-B) Domain Scores from Visit 3 (2nd baseline visit, pre-HS treatment) to Visit 5 (post-HS treatment period) [Срок оценки: Day 1 (Visit 2) up to 5 weeks (Visit 5)]
• Change in Quality of life for Bronchiectasis (QOL-B) Respiratory Symptoms Domain Sputum Score from Visit 3 (2nd baseline visit, pre-HS treatment) to Visit 5 (post-HS treatment period) [Срок оценки: Day 1 (Visit 2) up to 5 weeks (Visit 5)]
• Change in Lung Clearance Index (LCI) as measured by Multiple Breath Washout (MBW) from Baseline (mean from Visit 2 and visit 3, pre-HS treatment) to Visit 5 (post-HS treatment period) [Срок оценки: Day 1 (Visit 2) up to 7 weeks (Visit 5)]

Критерии участия

Критерии включения

• Adults >18 years of age able to provide informed consent
• Diagnosis of bronchiectasis confirmed on prior chest computed tomography (CT), involving at least 2 lobes, with at least one lobe of involvement in the right lung
• Forced expiratory volume in one second (FEV1) % predicted > 40%, inclusive
• History of prior bronchiectasis exacerbations (requiring antibiotics)
• Chronic cough

Критерии исключения

• Diagnosis of cystic fibrosis (CF), primary ciliary dyskinesia (PCD), chronic aspiration, or predominantly traction bronchiectasis due to interstitial lung disease (ILD)
• Unable or unwilling to undergo HS washout period of 2 weeks preceding first baseline MCC scan
• Concomitant inhaled acetylcysteine or dornase alfa use
• Recent pulmonary exacerbation in preceding 4 weeks
• History of intolerance to HS (bronchospasm, hemoptysis)
• History of significant hemoptysis (>60 ml) within the preceding 3 months
• Chronic supplemental oxygen use at rest
• Severe asthma, as reflected by need for chronic oral corticosteroids (>10mg/day), asthma biologic therapies, hospitalization for status asthmaticus within the past year, or bronchiectasis felt to have resulted from chronic asthma
• Significant bronchodilator response (>15% increase in FEV1 or forced vital capacity \[FVC\]) on pre-post spirometry testing during screening visit
• Failed HS tolerability test (HSTT) at screening, as indicated by:
• Intolerable symptoms after HS administration
• Decline in FEV1 % predicted by >20% when measured 15 min after HS administration
• Decline in FEV1 % predicted between 10-20% when measured at 15 min that does not recover to within 10% of baseline without intervention 1 hour post HS test dose
• Smoking/vaping, any substance within the past year, or >10 pack-years of cigarette use over their lifetime
• More than 2 chest CTs in the past year or a combination of procedures believed to have exposed the lungs to >150 millisieverts (mSv)
• Current/recent participation in other interventional studies for NCFB, allowing for appropriate wash-out time
• Pregnancy

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of North Carolina at Chapel Hill — Chapel Hill

Идентификаторы

NCT: NCT06242795 · 23-0185 · 005177D123

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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