Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Baseline MCC (Ave60Clr; Average Clearance Over 60 Minutes)
研究概览
简要总结
The purpose of this study is to measure mucociliary clearance (MCC) in groups of subjects with the disease Primary Ciliary Dyskinesia (PCD) caused by mutations in different genes, and compare to healthy subjects. Some of these genes are associated with a milder clinical phenotype. This study seeks to determine if the milder phenotype is a result of mutations in a set of specific genes. The hypothesis is that subjects with PCD caused by mutations in the milder group will maintain a low, but significant rate of mucociliary clearance, while patients with mutations in genes in the more severe group will have a complete absence of mucociliary clearance. These studies will help inform future treatment strategies.
详细描述
Participants will undergo screening with basic physical exam and lung function testing at the start of the study. Participants will then inhale a radiolabeled substance and undergo medical imaging to measure the clearance of mucus in the airways. Albuterol will be administered after the first imaging is completed. Lung function testing will be repeated. Finally, medical imaging will be repeated two more times to further look at clearance of mucus in the lungs. The study will be completed in one day and will last about 6 hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 90 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, immunodeficiency, history of tuberculosis
- •Any acute infection requiring antibiotics within 4 weeks of study.
- •Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
- •Medications which may impact the results of the study treatment, or may interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents)
- •Active smoking to include e-cigarettes within 1 year of the study, or lifetime of > 10 pack years of smoking
- •History of vaping or current vaping.
- •Viral upper respiratory tract infection within 4 weeks of challenge.
- •Radiation exposure history in the past year which would be outside the safe levels
- •Pregnant or lactating women will also be excluded since the risks associated with radiation are unknown and cannot be justified
- •Use of the following medications:
- •Use of beta blocking medications
- •Receipt of Live Attenuated Influenza Vaccine (LAIV), also known as FluMist , within the prior 30 days, or any vaccine within the prior 5 days
- •Multivitamins, Vitamin C or E or herbal medications in the 4 days prior to the treatment visit
- •Non-steroidal anti-inflammatory drugs in the 4 days prior to the treatment visit.
- •Allergy/sensitivity to study drugs or their formulations:
- •Known Immunoglobulin E (IgE) mediated hypersensitivity to albuterol
- •Physical/laboratory indications:
- •Temperature > 37.8 degrees Celsius (C)
- •Subjects >15 years- Systolic BP >150 mm hg or < 90 mm Hg or diastolic BP> 90 mm Hg or < 50 and Subjects 12-15 years - Systolic BP > 130 mmHg or < 80 mmHg or diastolic BP > 80 or <40
- •Oxygen saturation of < 93 percent
- •Inability or unwillingness of a participant to give written informed consent.
研究组 & 干预措施
Genotypes associated mild phenotype
Subjects with 2 confirmed mutations in RSPH1, Radial Spoke Head Component 9 (RSPH9), Radial Spoke Head Component 4A (RSPH4a), or Dynein Axonemal Heavy Chain 11 (DNAH11). This group may also include subjects with mutations in newly identified genes that are associated with a milder clinical phenotype.
干预措施: Albuterol (Drug)
Genotypes associated mild phenotype
Subjects with 2 confirmed mutations in RSPH1, Radial Spoke Head Component 9 (RSPH9), Radial Spoke Head Component 4A (RSPH4a), or Dynein Axonemal Heavy Chain 11 (DNAH11). This group may also include subjects with mutations in newly identified genes that are associated with a milder clinical phenotype.
干预措施: Technetium99m - Sulfur Colloid (Tc99m-SC) (Diagnostic Test)
Genotypes associated with severe phenotype
Subjects with 2 confirmed mutations in DNAH5, Dynein Axonemal Intermediate Chain 1 (DNAI1), Coiled-Coil Domain Containing 39 (CCDC39), or Coiled-Coil Domain Containing 40 (CCDC40). This group may also include subjects with mutations in newly identified genes that are associated with a more severe clinical phenotype.
干预措施: Albuterol (Drug)
Genotypes associated with severe phenotype
Subjects with 2 confirmed mutations in DNAH5, Dynein Axonemal Intermediate Chain 1 (DNAI1), Coiled-Coil Domain Containing 39 (CCDC39), or Coiled-Coil Domain Containing 40 (CCDC40). This group may also include subjects with mutations in newly identified genes that are associated with a more severe clinical phenotype.
干预措施: Technetium99m - Sulfur Colloid (Tc99m-SC) (Diagnostic Test)
Healthy Control
Healthy subjects with no pre-existing lung disease.
干预措施: Albuterol (Drug)
Healthy Control
Healthy subjects with no pre-existing lung disease.
干预措施: Technetium99m - Sulfur Colloid (Tc99m-SC) (Diagnostic Test)
结局指标
主要结局
Baseline MCC (Ave60Clr; Average Clearance Over 60 Minutes)
时间窗: 60 minutes
The average percent clearance in subjects with Primary Ciliary Dyskinesia (PCD) caused by mutations associated with mild and severe clinical phenotypes. Prior to each MCC study, a transmission Co57 scan will be performed to define the lung boundaries, to assign regions of interest, and to normalize these regions for lung volume differences. Radiolabeled Tc99m-sulfur colloid will be delivered using a modified Pari-LC Star nebulizer. The subject will then (within a minute of final inhalation maneuver) be seated in front of a large-field-of-view gamma camera to begin acquiring consecutive 2 minute images. The first two-2-minute images will provide initial, time zero activity (i.e. 100% retention) followed by the same imaging at the start of every 10-minute period until 1 hour has passed to assess baseline MCC. Clearance will be determined by measuring the decrease in radiolabeled Tc99m-sulfur colloid in the lungs over time.
次要结局
- Change in MCC (Ave120Clr-Ave60Clr;Average Clearance Between 60 and 120 Minutes)(120 minutes)