The Role of Cholecystokinin and the Cholecystokinin Receptor in the Airway Smooth Muscle of Asthmatics
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Change in Airway Smooth Muscle (ASM) Cholecystokinin (CCK) and Cholecystokinin Receptor (CCK-AR) expression with coconut oil supplementation
研究概览
简要总结
In this proof of concept study, the investigators aim to determine if supplementation with coconut oil causes an increase in cholecystokinin and cholecystokinin receptor expression in the airway smooth muscle of lean asthmatics, and whether these changes correlate with changes in airway stiffness (estimated by bronchodilator reversibility, airway reactivity, and airway resistance) or symptom control.
The investigators propose a 5 week, single center trial in 20 lean patients with mild asthma (not taking inhaled corticosteroids) aged 18 and older. Subjects will supplement their usual diets with 3 tablespoons of coconut oil, a commercially available oil with high dodecanoic acid content, for 3 weeks. To quantify changes in airway smooth muscle cholecystokinin and cholecystokinin-receptor expression, each subject will undergo bronchoscopy with endobronchial biopsies before and after coconut oil ingestion.
For the secondary analysis, subjects will also complete spirometry with bronchodilator testing, methacholine challenge, body plethysmography, and an Asthma Control Questionnaire (ACQ) before and after the dietary intervention. This information will be used to compare the changes in airway smooth muscle cholecystokinin and cholecystokinin receptor expression to changes in bronchodilator reversibility, airway reactivity, airway resistance, and symptom control.
In the exploratory aims, the investigators will correlate the changes in airway smooth muscle cholecystokinin and cholecystokinin receptor expression with changes in FEV1 and peak flow measurements.
The investigators therefore hope to elucidate information about the mechanistic role of cholecystokinin in airway smooth muscle stiffness and contraction.
详细描述
20 lean (BMI<25) nonsmokers at least 18 years of age with mild asthma will be recruited from the Asthma Research Center database. A sample size of 12 asthmatics is needed to have 80% power to detect a 3-fold increase in cholecystokinin (CCK) post dodecanoic acid ingestion at alpha level of 0.05, assuming the standard deviation is ≤2.25 in cycle scale. To account for probable incomplete retention, 20 subjects will be recruited. While the calculated standard deviation is 1.775, the investigators chose to base our calculations off of a larger standard deviation because of our small sample size.
Study subjects will be asked to come to 5 visits, described in detail below.
Visit 1: Eligibility Screen Pre-screened Volunteers will be asked not to take their short acting bronchodilators or ipratropium within 6 hours of this visit. They will complete a medical history that includes detailed information about past and current asthma medications, ACQ, physical exam with weight/BMI check and spirometry with bronchodilator testing. They will undergo body plethysmography to measure baseline airway resistance.
Visit 2: Eligibility Screen, methacholine challenge Subjects will return at any point during the 1-4 weeks allowed between visits 1 and 3. They will be told to not to take their short acting bronchodilators or ipratropium within 8 hours of this visit and to avoid caffeine (coffee, tea, cola drinks, and chocolate) the day of the visit. This visit will be short, comprised only of a methacholine challenge, to measure baseline airway reactivity.
Visit 3: Bronchoscopy Eligible subjects will be asked not to take aspirin, anticoagulant (e.g., warfarin) or antiplatelet (e.g., clopidogrel) medication in the 7 days prior to this second visit. They will also be told not to eat or drink within 6hrs of the visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Male and female participants, age 18 years and older at enrollment
- •Never smokers or <10 pack year smoking history
- •Body mass index (BMI) <25
- •Clinical history consistent with asthma for >1 year
- •No use of an inhaled corticosteroid in the prior 3mo
- •Ability to perform reproducible spirometry according to ATS criteria
- •Baseline Forced expiratory volume in 1 second (FEV1) ≥ 60% predicted
- •Presence of bronchodilator reversibility, as defined by a minimum of 12% and ≥ 200 ml improvement after 4 puffs of albuterol, each 90 μg
- •Ability to provide informed consent, as evidenced by signing a copy of the consent form approved by the Institutional Review Board.
排除标准
- •Supplementation with fatty acids within the last 3 months
- •Pregnant or nursing
- •History of smoking (cigarettes, cigars, pipes, marijuana or any other substances) within the past 1 year, or >10 pack-years total
- •Use of inhaled corticosteroid in the prior 3 mo
- •Lack of bronchodilator response to 4 puffs of albuterol
- •Medical contraindication to bronchoscopy/biopsy, i.e inability to stop aspirin, anticoagulant, or antiplatelet at any point during the study; coagulopathy; inability to lay flat; asthma exacerbation requiring corticosteroids in the preceding 4 weeks; history of adverse reaction or allergy to sedatives; history of difficult airway, or past difficulty with intubation
- •Major medical problems prohibiting study participation, i.e presence of chronic or active lung disease other than asthma or history of unstable significant medical illness other than asthma
- •Evidence that the participant may be non-adherent to medication regimen, or may move from the performance site area before trial completion
结局指标
主要结局
Change in Airway Smooth Muscle (ASM) Cholecystokinin (CCK) and Cholecystokinin Receptor (CCK-AR) expression with coconut oil supplementation
时间窗: 3 weeks
次要结局
- Change in ASM CCK and CCK-AR expression with coconut oil supplementation, versus change in Asthma Control Questionnaire (ACQ) score.(3 weeks)
- Change in ASM CCK and CCK-AR expression with coconut oil supplementation, versus change in bronchodilator reversibility.(3 weeks)
- Change in ASM CCK and CCK-AR expression with coconut oil supplementation, versus change in bronchial hyperresponsiveness (PC20).(3 weeks)
- Change in ASM CCK and CCK-AR expression with coconut oil supplementation, versus change in airway resistance(3 weeks)
研究者
Elliot Israel, MD
Elliot Israel, MD
Brigham and Women's Hospital