Clinical trial NCT03122795: Sinonasal Microbiome Transplant as a Therapy for Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
Official title: Sinonasal Microbiome Transplant as a Therapy for Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Rhinosinusitis (Diagnosis)
Lead sponsor: Region Skane
Sponsor class: OTHER
First posted: 2017-04-21
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients and donors who meet the inclusion criteria will be recruited and inclueded and put through the study in a cumulative fashion.
Primary purpose: TREATMENT

Brief summary: Chronic rhinosinusitis (CRS) is a disease associated with impaired quality of life and substantial societal costs. Though sometimes co-appearing with other conditions, such as asthma, allergy, and nasal polyps, many cases present without co-morbidities. Micro-biological diagnostic procedures are frequently undertaken, but the results are often inconclusive. Nevertheless, antibiotics are usually prescribed, but invariably with limited and temporary success. Accordingly, there is a need for new treatments for CRS.

Recent studies indicate that the sinuses are colonized by a commensal microbiome of bacteria and that damage to this natural microbiome, by pathogens or antibiotics, may cause an imbalance that may promote CRS. Therefore, treatments that restore the commensal microbiome may offer an alternative to current protocols. Arguably, as suggested by studies on patients with intestinal infections (next paragraph), one such possibility may be to transfer a "normal microbiome" to patients with CRS.

A disrupted microbiome is linked to intestinal clostridium difficile infections. Probiotic restitution therapy may be effective even in cases recalcitrant to antibiotic treatment. However, a key to effective probiotic restitution is selecting the bacteria that facilitate regrowth of normal microbiome. As an answer to this, researchers have chosen to simply transplant the entire microbiome from a healthy donor. In the case of clostridium difficile infection in the form of faecal transplants.

In this study, we will examine the possibility to treat patients with chronic rhinosinusitis without polyps (CRSsNP) with complete sinonasal microbiomes obtained from healthy donors. Our analysis will focus on symptoms and signs of disease as well as on nasal inflammatory and microbiological indices.

Detailed description: Over the last few years the theory of a damaged microbiome as a cause or promoting factor behind chronic rhinosinusitis has gained increasing interest from the scientific community.

A number of studies aimed at investigating the microbiota of the nose and paranasal sinuses in health and disease has been published with very varying outcomes. Furthermore, other studies have been aimed at probiotic treatment of sinonasal disease either locally or through immunologic manipulation via the gastrointestinal microbiota.

A problem common to all these studies is that studies examining the normal nasal microbiota have identified a great amount of different bacterial species. It is as of today not known which individual species or combinations of species that promotes health.

The probiotic assemblages examined in previous studies have consisted of one or a combination of a few bacterial species.

Probiotic restitution therapy has been proven very effective for intestinal clostridium difficile infections. The restitution therapy has then consisted of transplantation of a complete microbiome from a healthy donor in the form of a faecal transplant.

In this study the investigators aim at recruiting patients suffering from chronic rhinosinusitis without polyps (CRSsNP) and healthy participants without any history sinonasal disease. The patients and the healthy participants will be examined for infectious diseases in a manner similar to other medical transplant procedures to minimize the risk for the recipients. The patients will then be treated with antibiotics to reduce the bacterial load of the nose and the paranasal sinuses. After the patient has finished the antibiotic treatment a microbiome transplant will be harvested from the healthy participant as a nasal lavage. The raw lavage fluid will then be used to transplant the microbiome to the patient. The procedure will be repeated for five consecutive days.

The outcome measures analysed will focus on subjective sinonasal health and symptoms of the patients but also include nasal inflammatory and microbiological indices.

Eligibility criteria: Inclusion criteria (patient)

* 2 nasal symptoms: 1 of which must be nasal obstruction or discoloured discharge.
* Sinusitis verified by endoscopy or CT-scan.
* Duration \> 12 weeks.
* Previous surgery with patent ostia to the diseased sinuses.
* Signed informed consent to participate in the study.

Inclusion criteria (donor)

* No history of sinonasal or lower airway disease within the last 2 years other than the common cold.
* Accepted as a donor by the patient.
* Signed informed consent to participate in the study.

Exclusion criteria (patient)

* Nasal polyposis.
* Antibiotic treatment within the last 4 weeks.
* On-going or recent participation in another clinical trial.
* Any medication that may affect the results in an unpredictable manner.
* Immune deficiency.
* Allergy to amoxicillin or clavulanate potassium and clarithromycin.
* Pregnancy or breastfeeding.

Exclusion criteria (donor)

* Chronic rhinosinusitis.
* Acute rhinosinusitis within the last two years.
* Nasal polyposis.
* Asthma.
* Antibiotic treatment within the last 4 weeks.
* On-going or recent participation in another clinical trial.
* Clinical findings of sinonasal disease at the inclusion visit.
* Findings in the pre-study pathogen scan that makes the donor unsuitable.
* Pregnancy or breastfeeding.

Primary outcomes:
measure: SNOT-22
timeFrame: Day 1 to day 106
Secondary outcomes:
measure: Lund Kennedy endoscopy score
timeFrame: Day 1 to day 106
measure: Subjective symptom score
timeFrame: Day 1 to 106.
measure: Inflammatory burden
timeFrame: Day 1 to day 106
measure: Microflora
timeFrame: Day 1 to day 106
Other outcomes:
Locations:
city: Helsingborg
country: Sweden
facility: Departement of ORL
Study officials:
affiliation: Region Skåne
name: Anders Mårtensson, MD
role: PRINCIPAL_INVESTIGATOR
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