Sinonasal Microbiome Transplant as a Therapy for Chronic Rhinosinusitis (CRS): A Randomized , Placebo Controlled Cross Over Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Region Skane
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Sino-nasal outcome test 22 (SNOT-22) (min 0 - max 110 higher being worse)
研究概览
简要总结
Chronic rhinosinusitis (CRS) is a disease associated with impaired quality of life and substantial societal costs. Much is still uncertain regarding the underlying etiology of the disease. Current treatment protocols are based on observed effects rather than a mechanistic understanding of the disease and thus patients often report unsatisfactory symptom reduction despite treatment with maximal medical therapy and even surgery.
CRS is subgrouped phenotypically based on whether or not polyps are observed. Recently an endotypical differentiation reflecting the underlying inflammatory profile has been recommended as well, especially for research.
Increasing interest in the role of the commensal microbiome inflammatory diseases has followed a growing understanding of its profound impact on the human immune system. Current research indicates that instability and dysfunction of the microbiome is linked to inflammatory disease rather than compositional differences. Previous research has shown that microbiome transplants are effective in restoring the commensal microbiome and reducing inflammation in gastrointestinal disease and in a previous pilot study the investigators showed that sinonasal microbiome transplants are feasible and were associated with reduced symptoms in chronic rhinosinusitis without nasal polyps (CRSsNP).
This study will examine if the positive effect on patients symptoms observed in a previous pilot study are sustained in a placebo controlled, blinded study. In addition to this the study will also examine any differences in microbiome structure, stability, and function between patients with CRS and healthy donors as well as any correlation to disease phenotype or inflammatory endotype.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(CRS-Patients):
- •2 nasal symptoms, 1 of which must be nasal obstruction or discolored discharge.
- •Sinusitis verified by endoscopy or CT scan
- •Duration > 12 weeks.
- •Signed informed consent to participate in the study.
排除标准
- •(CRS-Patients):
- •Antibiotic treatment in the last 3 months before study start.
- •Ongoing or recent participation in another clinical trial.
- •Any medication that might affect the results in an unpredictable manner.
- •Treatment with monoclonal antibodies (biologics).
- •Immunodeficiency other than low grade MBL deficiency.
- •Pregnancy or breastfeeding
- •Severe anatomical abnormalities.
- •SNOT 22 <
- •Inclusion Criteria (Donors):
- •No history of sinonasal or lower airway disease within the last two years other than the common cold.
- •Accepted as a donor by the patient.
- •Signed informed consent to participate in the study.
- •Exclusion Criteria (CRS-Patients):
- •Chronic rhinosinusitis.
- •Acute rhinosinusitis within the last two years.
- •Nasal polyposis
- •Antibiotic treatment within the last 3 months before the study start.
- •On going or recent participation in another clinical trial.
- •Findings in the pre study scan that makes the donor unsuitable.
结局指标
主要结局
Sino-nasal outcome test 22 (SNOT-22) (min 0 - max 110 higher being worse)
时间窗: 14 days before intervention, on the first day of intervention, 2 and 3 months after intervention and as a follow up 1, 2 and 3 years after the study.
Subjective symptom grading of the patients will be used to asses efficacy of the treatment and the duration of the treatment effect.
次要结局
- Endoscopy(2 weeks before intervention, 3 months after intervention and as a follow up 1, 2 and 3 years after the study.)
- Total Nasal Symptom Score. (min 0 - max 9)(14 days before intervention, daily during the five days of intervention, 2 and 3 months after intervention and as a follow up 1, 2 and 3 years after the study.)
- Metagenomics(6 and 2 weeks before intervention, 8 and 12 weeks after intervention and as a follow up twice with 4 weeks apart 1, 2 and 3 years after the study.)
- Metabolomics(2 weeks before intervention and 12 weeks after intervention and as a follow up 1, 2 and 3 years after the study.)
- Inflammatory markers(2 weeks before intervention, 12 weeks after intervention and as a follow up 1, 2 and 3 years after the study.)
- Adverse events(Entire study duration. Total study duration is 1 year and 5 months for the study and 3 years of follow up.)