Immunoglobulin Replacement Therapy for Immunoglobulin G Subclass 2 Deficient Patients With Bronchiectasis- A Proof of Concept Study
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Change in sputum bacterial load
研究概览
简要总结
Bronchiectasis is a common chronic lung condition where patients have permanent airways damage leading to daily symptoms of cough, sputum production and recurrent respiratory tract infections.
Preliminary studies in our research group have found a severe deficiency of the immune system as a rare cause of bronchiectasis (called immunoglobulin G subclass 2 deficiency) and occurs in about 1 in 20 bronchiectasis patients. The pilot work shows that these patients have more chest infections and their lung function deteriorates more rapidly.
There are no trials to date to guide doctors to decide whether we should replace this deficiency from donated blood or not. The aim with treatment is to prevent disease progression and avoid the need for long term antibiotics.
This trial will help us understand how this treatment works and its acceptability to patients. This study will help us decide whether investigators should pursue future formalised trials in many centres throughout the UK and how investigators should evaluate such a treatment.
We are looking to recruit 20 patients to this study 10 of which will receive weekly replacement therapy and the remaining 10 will receive standard care.
详细描述
Background What is bronchiectasis? Bronchiectasis is a chronic disabling condition due to permanently inflamed and damaged airways with patients suffering chronic cough, chronic sputum production and recurrent infections affecting 4-6 per 1,000 populations in the UK.
Causes of bronchiectasis There are a variety of causes of bronchiectasis with past infection being the commonest cause (29-42%). In about 30-53% no cause can be identified in bronchiectasis. National guidelines recommend screening for causes that are potentially treatable including immune deficiency, allergic bronchopulmonary aspergillosis, active environmental bacterial infection and cystic fibrosis as they all have therapies that may alter the disease progression.
Immunoglobulins in bronchiectasis Immunoglobulin A (IgA) and Immunoglobulin G (IgG) are the most common antibodies found in the lung, where they opsonize pathogens and protect the body from infection together with neutrophils and macrophages. Most bronchiectasis patients show higher than normal IgG and IgA antibody levels, which reflects the high degree of recurrent lung infections and chronic inflammation.
IgG has four subclasses (1-4), which bind to and opsonize different kinds of antigens. IgG2 primarily binds polysaccharides and carbohydrates that are found in bacterial capsules, the cell wall in gram-positive bacteria and the O-antigen of lipopolysaccharides found on the outer membrane of gram-negative bacteria, which makes IgG2 an important part of bacterial clearance in the lung.
The frequency of IgG2 deficiency in the general healthy population lies between 2 to 20% (N = 106). Paediatric studies show IgG2 deficiency was the most frequent IgG subclass deficiency, and in their study 10% already had bronchiectasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
1 group receiving standard care
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Active arm
Weekly subcutaneous immunoglobulin therapy (0.1g/Kg) Cuvitru 20% Injectable Solution for 1 Year
干预措施: Cuvitru 20 % Injectable Solution (Drug)
结局指标
主要结局
Change in sputum bacterial load
时间窗: 52 weeks
With IgG replacement therapy, does the sputum bacterial load change in treated versus untreated group
Proportion with bacterial load >=10(6) colony forming units/ml
时间窗: 52 weeks
With IgG replacement therapy, does the frequency with \>=10(6) colony forming units/ml change in treated versus untreated group?
次要结局
- Change of total IgG and subclasses(26 and 52 weeks)
- Change in sputum colour(26 and 52 weeks)
- Change in sputum volume(26 and 52 weeks)
- Change in sputum microbiome diversity(52 weeks)
- Change of forced expired volume in 1 second % predicted(26 and 52 weeks)
- Change of forced expired volume in 1 second(26 and 52 weeks)
- Change of forced vital capacity(26 and 52 weeks)
- Change of forced vital capacity % predicted(26 and 52 weeks)
- Change of incremental shuttle walk test(26 and 52 weeks)
- Change of cough related quality of life using Leicester Cough Questionnaire mean score(26 and 52 weeks)
- Change of cough related quality of life using Leicester Cough Questionnaire with 1.3 Unit or greater improvement(26 and 52 weeks)
- Change of quality of life using St George's Respiratory Questionnaire with 4Unit or greater improvement(26 and 52 weeks)
- Change of quality of life using St George's Respiratory Questionnaire mean score(26 and 52 weeks)
- Change of sputum myeloperoxidase(26 and 52 weeks)
- Change of sputum elastase(26 and 52 weeks)
- Change of sputum interleukin 8(26 and 52 weeks)
- Change of serum white cell count(26 and 52 weeks)
- Change of serum C reactive protein(26 and 52 weeks)
- Change of serum erythrocyte sedimentation rate(26 and 52 weeks)
- Change of serum intercellular adhesion molecule 1(26 and 52 weeks)
- Change of phagocytosis and killing of Pseudomonas aeruginosa(26 and 52 weeks)
- Change of phagocytosis and killing of Staphylococcus aureus(26 and 52 weeks)
- Proportion with specific antibody deficiency(Baseline)
- Time to first exacerbation requiring antibiotic therapy(52 weeks)
- Number of exacerbations(52 weeks)
- Frequency of exacerbations(52 weeks)
- Number of participants with side effects(26 and 52 weeks)
- Compliance rates of IgG therapy(26 and 52 weeks)
- Completion rates of IgG therapy(26 and 52 weeks)