Effect of House Dust Mite Allergen Challenge in Persons Using 1200 mg Gamma Tocopherol Supplements
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Post-treatment change in concentration of house dust mite-induced eosinophils in nasal lavage fluid (NLF), compared to pre-treatment baseline.
研究概览
简要总结
Twenty, house dust mite (HDM)-allergic non-smoking subjects with or without mild asthma between the ages 18-50 will be recruited. The primary endpoint will be nasal eosinophilia. Each volunteer will be screened with skin testing, pulmonary function testing and induced sputum. If eligible they will return for baseline nasal allergen challenge and lavage. Approximately two weeks later they will return for gamma tocopherol (gT) dosing visit. After completing 14 days of daily high dose (1200mg) gT, they will return for a second nasal allergen challenge. This visit will also include pulmonary function testing and blood draw. The purpose of this study is to determine if high dose gamma tocopherol therapy can reduce allergen induced nasal inflammation.
详细描述
This will be done using a single-group, prospective, descriptive proof of concept study design (Phase I) in which HDM-allergic adults will undergo baseline nasal allergen challenge and nasal lavage, then receive 2 weeks of treatment with gT followed by a second challenge and nasal lavage.
Primary outcome: Post-treatment change in concentration of house dust mite-induced eosinophils in nasal lavage fluid (NLF), compared to pre-treatment baseline.
Secondary outcomes: (a) NLF inflammatory mediators including eicosanoid products of COX-2 pathway, inflammatory cytokines relevant to innate immunity and allergic inflammation, cells other than eosinophils including neutrophils, total protein; (b) similar endpoints in induced sputum; (c) sub-analysis of all data for subjects with mild asthma.
Safety outcomes: Post-treatment change in coagulation markers (PT, PTT).
Study Protocol:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Specific allergy to house dust mite Dermatophagoides farinae confirmed by positive immediate skin test response.
- •Subjects may be enrolled with mild asthma if an FEV1 of at least 80% of predicted and
- •FEV1/FVC ratio of at least .70 (without use of bronchodilating medications for 12 hours), consistent with lung function of persons with mild episodic or mild persistent asthma is demonstrated. For the purpose of this protocol, an asthmatic individual will be defined as having a) positive methacholine challenge with a provocative concentration of methacholine producing a 20% fall in FEV1 (PC20 methacholine) with less than or equal to 10 mg/ml by the method used (see below); OR b) physician diagnosed asthma with symptoms and chronic daily therapy consistent with the mild asthma
- •Ability to withhold antihistamine medications for one week prior to study and one week prior to each nasal challenge visit.
- •Subjects must be able and willing to give informed consent. -
排除标准
- •Any chronic medical condition considered by the PI as a contraindication to the allergen challenge study including significant cardiovascular disease, diabetes requiring medication, chronic renal disease, bleeding disorder, or chronic thyroid disease.
- •Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months.
- •Use of systemic steroid therapy within the preceding 12 months for treatment of an asthma exacerbation.
- •Use of inhaled or nasal steroids, cromolyn or leukotriene inhibitors (Montelukast or Zafirkulast) within the past month (except for use of cromolyn exclusively prior to exercise).
- •Use of allergen immunotherapy.
- •Use of daily theophylline within the past month.
- •Use of nasal medications that might alter the response to nasal allergen challenge including anti-inflammatory and anti-histamine agents within one week of challenge.
- •Inability to withhold inhaled or oral bronchodilating medications for 12 hours prior to allergen challenge.
- •Pregnancy or nursing a baby.
- •Women of child-bearing age who are not using dependable contraception (such as birth control pills, IUD or estrogen patches) or who are not completely abstinent.
- •Cigarette smoking within the past 12 months of more than 1 pack/week.
- •Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- •Exacerbation of asthma more than 2x/week which would be characteristic of a person with moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
- •Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
- •Viral upper respiratory tract infection within 2 weeks of challenge.
- •Any acute infection requiring antibiotics within 2 weeks of challenge.
- •Participating in an allergen inhalation study within 2 weeks of this challenge or use of any investigational agent within last 30 days.
- •Use of tricyclics or beta-blockers.
- •Use of MAO inhibitors or any medications known to interfere with the treatment of anaphylaxis.
- •Subjects with a history of immunologic disease or undergoing immune suppression for cancer or other diseases.
结局指标
主要结局
Post-treatment change in concentration of house dust mite-induced eosinophils in nasal lavage fluid (NLF), compared to pre-treatment baseline.
时间窗: 4 hours
次要结局
- (a)NLF inflammatory mediators including eicosanoid products, inflammatory cytokines relevant to innate immunity and allergic inflammation, cells other than eosinophils, total protein (b)safety outcomes of cbc and coagulation factors(1 week)
研究者
Michelle Hernandez, MD
Investigator
University of North Carolina, Chapel Hill