Phase-II Randomized Control Trial of Nasal Microbiota Transplant Therapy in Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 5
- 主要终点
- Sino-Nasal Outcome Test (SNOT-22) - 22 Item Questionnaire
研究概览
简要总结
Chronic Rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal passage and paranasal sinuses that places significant burden on affected patients and global healthcare systems.
Current treatments for CRS such as long-term antibiotics, anti-inflammatory drugs, and surgery often reduce symptoms and signs of disease temporarily, however long-term results are much less satisfactory.
Recently, the theory of a damaged microbiome (dysbiosis) as a cause or promoting factor behind CRS has gained increasing evidence from the scientific community.
A condition of the gut with microbial dysbiosis (c.difficile) has previously employed microbiota transplant treatment with great success in long-term health outcomes. Such treatments are shown to repopulate bacterial microenvironment and restore protective commensal bacterial load.
A pilot study conducted by this study team trialed a novel intervention of a Nasal Microbiota Transplant in a small group of participants. Preliminary results suggested significantly improved CRS symptoms after treatment with a healthy donor microbiota transplant, compared to the pre-transplant baseline. The addition of a randomized-control trial with inclusion of a placebo group is the next step.
In this study, investigators aim to perform a two-arm, double-blinded, phase II randomized controlled clinical trial in order to assess the efficacy of a Nasal Microbiota Transplant against a placebo in a cohort of CRS patients without Nasal Polyps (CRSsNP).
详细描述
Current treatments for CRS such as long-term antibiotics, anti-inflammatory drugs, and surgery often reduce symptoms and signs of disease temporarily, however long-term results are much less satisfactory.
A microbiota therapy, as an alternative treatment to antibiotics, has the potential of improving outcomes for CRS patients long-term, whilst reducing the use of antibiotics in the community.
Several attempts of studies to define the role of microbiota of the nose and paranasal sinuses in health and disease have not yet been able to achieve a universal consensus. This is in part due to the significant inter-individual microbiota variation and complexity within humans. Such challenges have also limited the use of probiotic assemblages of one or a combination of few bacterial species in treatment of CRS.
The data derived from this study will add to our understanding of the role of the microbiome in the airways and its role in interfering with respiratory pathogens and host immunity. This is likely to have implications for CRS microbiome-based therapies, and also other potentially related respiratory conditions such as asthma, and chronic obstructive pulmonary disease (COPD).
In this study, investigators will recruit patients suffering from chronic rhinosinusitis without polyps (CRSsNP) and healthy participants that do not have a history of sinonasal disease. The sinus microbiome transplants will occur over a 2 week period, with regular follow up for up to 6-months post intervention. Main outcomes include change in disease severity, symptom severity, inflammatory changes, and microbial composition across the study period. Successful results from this trial may pave the way for a novel therapeutic for CRS patients.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
A biostatistician, not involved in assignment or care of the trial participants, will generate the randomisation sequence with a computerised random number generator. A research assistant, not involved in any other aspect of this study, will place the assigned treatments into sealed envelopes.
Participants (Patients and donors) will be blinded from knowing if they are in the intervention group or the control group. The nurse and doctors attending to the participants will also be blinded. A member of the study team who will prepare the Nasal Microbiota Transplant therapy will not be masked. The person doing the analysis will be masked.
入排标准
- 年龄范围
- 18 Years 至 80 Years（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
- •Exclusion criteria (patient):
- •Aged <18 or >80 years
- •Allergy to amoxicillin or clavulanate potassium and Clarithromycin.
- •Excessive Nasal polyposis
- •Antibiotic treatment in the last 4 weeks
- •Patients with a history supporting a diagnosis of immune deficiency will be tested (Immunoglobulin A (IgA), Immunoglobulin M (IgM), Immunoglobulin G (IgG) and IgG subclasses, MBL) and /or are immunocompromised due to disease and / or medication ( e.g., insulin dependent diabetes mellitis, systemic corticosteroids)
- •Patients who live with someone who is severly immunocompromised.
- •Patients with cystic fibrosis or ciliary dyskinesia
- •Patients who have been on an active investigational therapy within 2 months of screening
- •Patients who have clinically significant laboratory abnormalities
- •Patients who are pregnant, breast feeding or planning to become pregnant during the study
- •Patients who are not willing to use a double barrier method of contraception during the study that is:-
- •females must use contraceptive pill or Intra-uterine device (IUD) or similar and condoms
- •males must use condoms and spermicidal gel
- •Patients currently on any medication that may affect the results in an unpredictable manner
- •The patient does not agree to comply with or is unable to meet all study requirements for the duration of the study period
- •Patients deemed by the investigator to be unsuitable for participation in the study
- •Patients who have had Coronavirus-19 (COVID-19) within the last month.
- •Exclusion criteria (donor):
- •Findings in the prestudy pathogen scan that makes the donor unsuitable. Prestudy pathogen scan: Prior to first donation, the donors will be tested for HIV, Human T-lymphotropic virus 1 and 2, Hepatitis B and C, Syphilis, Tuberculosis, Herpes Simplex (HSV 1 and 2), Varicella Zoster (VZV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Methicillin-resistant Staphylococcus aureus (MRSA) and a standard panel for sinonasal pathogens (Pneumococci, H. Influenza, Beta-streptococci and M. Catarrhalis).
- •Donors who have had COVID-19 within the last 2 months.
- •If the donor is positive for Herpes Simplex, CMV or EBV they will be considered unsuitable as a donor for a patient negative for the same pathogen. If the donor is positive for any other pathogen they will be considered unsuitable as a donor entirely.
结局指标
主要结局
Sino-Nasal Outcome Test (SNOT-22) - 22 Item Questionnaire
时间窗: Week 1 (Day 1) to Week 20
Change of burden of disease as measured by the SNOT-22 (22 item sinonasal outcome test) questionnaire in patients. Each item graded 0-5. Minimum score 0, Maximum 105 Interpretation: Higher score indicates poorer disease control.
次要结局
- Cytokine level - Interleukin 2 (IL-2)(Week 1 (Day 1) to Week 20)
- Characterisation of microbiome within effective donors as compared to ineffective donors(Week 1 (Day 1) - Week 2 (Day 9))
- Adverse events of Participating Patients(From the day participating patients give signed consent (2-4 weeks before baseline) until the day of their End of study visit (Up to 33 weeks).)
- Cytokine level - Interleukin 13 (IL-13)(Week 1 (Day 1) to Week 20)
- Cytokine level - Interleukin 4 (IL-4)(Week 1 (Day 1) to Week 20)
- Lund-Kennedy endoscopic assessment score(Week 1 (Day 1) to Week 20)
- Characterisation of nasal microbiome in study participants(Week 1 (Day 1) to Week 20)
- Cytokine level - Interleukin 5 or (IL-5)(Week 1 (Day 1) to Week 20)
- Cytokine level - Interleukin 6 (IL-6)(Week 1 (Day 1) to Week 20)
- Cytokine level - Interleukin 10 (IL-10)(Week 1 (Day 1) to Week 20)
- Cytokine level - Interferon gamma (IFN-γ)(Week 1 (Day 1) to Week 20)