The Effects of Salbutamol on Mannitol Induced Cough Responses in Healthy Controls
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Primary Outcome - Emax
研究概览
简要总结
The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing healthy controls with no evidence of bronchoconstriction (PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses) and if salbutamol can affect this. This is a double-blind, placebo-controlled analysis in healthy controls assessing the effects of salbutamol on mannitol induced cough.
详细描述
The study will have a maximum of 4 visits separated by at least 24 hours. The first 2 visits will determine eligibility. All eligible subjects will be invited back for a third and a fourth visit.
Screening Period (Visits 1 and 2) - For All Subjects Eligible subjects will be identified during the initial screening procedures with measures of spirometry, hyperresponsiveness to methacholine, complete history, physical examination, allergen skin test, and mannitol cough challenge. The screening procedures will be conducted over 2 separate visits.
Effects of Salbutamol (Visit 3 and 4) - For Healthy Control Subjects, Twenty subjects with no evidence of asthma will return for visit 3 and 4. These visits must be at least 24h apart and no longer than 7 days. Health controls will first receive salbutamol 2.5mg or saline placebo via a nebuliser and 15 mins later the forced expiratory volume at one second (FEV1) measured. Subjects will then undergo a mannitol cough challenge exactly like the previous mannitol cough challenges. These data will be used for determining the effects of salbutamol on mannitol-induced cough.
Visit Windows Each visit must be separated by a minimum of 24 hours, and a maximum of 7 days. Study visits can be performed in the morning or afternoon, however for each subject the timing should be consistent with Visits 2 at the same time of day ± 2 hours
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Able to understand and give written informed consent.
- •Male and female volunteers 18 through 65 years of age.
- •No airway hyperresponsiveness as determined by methacholine PC20>16mg/ml or mannitol PD15 > 635 mg, or < 10% incremental fall in FEV1 between consecutive mannitol doses.
- •Fall in FEV1 of ≤ 5% after any mannitol dose during mannitol challenge compared to baseline FEV1 at 0 mg at screening mannitol challenge (Visit 2).
- •Baseline FEV1≥ 80% of the predicted value.
- •Demonstrate cough response to inhaled mannitol.
排除标准
- •Current or former smoker with >10-pack-year history
- •Current or previous history of other significant respiratory disease
- •Significant systemic disease, including history of current malignancy or autoimmune disease
- •Pregnancy or breastfeeding.
- •Use of corticosteroids within 28 days prior to the first study visit.
- •Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of study visits or aspirin with 7 days of study visits
- •Use of antihistamines including those in cold and allergy medications within 72 hours of study visits
- •Use of caffeine-containing products within 4 hours of study visits
- •Use of ACE inhibitors
- •Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex including but not restricted to tricyclic anti-depressants, pregabalin, gabapentin, codeine, tramadol, or any other opioid.
- •Unwillingness or inability to comply with the study protocol for any other reason
研究组 & 干预措施
Healthy Control - Active Arm
Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4.
干预措施: Salbutamol 5mg/mL (Drug)
Healthy control - Placebo Arm
Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized 0.9% Saline given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4.
干预措施: Sodium Chloride 0.9% Inhl 3Ml (Drug)
结局指标
主要结局
Primary Outcome - Emax
时间窗: Through study completion, an average of 1 year
The effect of salbutamol on mannitol induced coughs Emax - the maximum number of coughs at any dose of mannitol.
次要结局
- C2(Through study completion, an average of 1 year)
- C5(Through study completion, an average of 1 year)
- Cough dose response curves(Through study completion, an average of 1 year)
- ED50(Through study completion, an average of 1 year)
- Cumulative number of coughs(Through study completion, an average of 1 year)
研究者
Gail Gauvreau
Professor Department of MEdicine
McMaster University