Treating Chronic Rhinosinusitis - SNOT transplant studies (Full version)

Dr. Amin Javer, MD, FRCSC, FARS, Otolaryngologist

Duration: 7 minutes

This is a trial that has two parts to it. The first part has just been completed and published. It is called the Sino-nasal Microbial Transplant trial or SNMT; otherwise also known as a SNOT transplant study. Most people usually laugh at that - but that's exactly what we're doing.

The group of patients that are the most difficult to treat in the sinus world are patients that get chronic sinusitis that never goes away despite maximal medical and surgical management. These are patients that have had surgery and failed on maximum medical therapy. Essentially, nothing we do works to fix their sinus problems. The reason, in our opinion, is that the chronic inflammation in their sinuses is secondary to a microbiome that has gone awry. This is what we call a “dysbiotic” microbiome. The microbiome contain the microbes that live in our bodies and on our bodies, ie within our living space – and keep things healthy for us. They amount to more than 10X the cells that make up our bodies. When this microbiome becomes dysbiotic – or loses it’s health, the body becomes unhealthy, and thereby activates inflammatory cascades resulting in inflammation.

The big question we've had so far is, what comes first: is it inflammation that damages the microbiome or does a damaged microbiome cause inflammation – a typical chicken or the egg question? We have not yet determined the answer to this question. We noted evidence of biofilm within the sick sinuses and felt that if we could correct the microbiome, we may subsequently improve and possibly clear the inflammation. This has been done previously in fecal microbial transplants which have become very popular and have saved many lives, and continues to gain popularity worldwide. In fecal microbial transplant, what they do is take healthy fecal material and put it in the bowel that is sick. What they found is that the bowel re-gained a healthy microbiome and the patient got better. We felt that the altered or sick micrbiome in the sinuses may be able to be corrected via a similar idea, ie place healthy sinonasal microbiome in a sick sinus and see what happens.

We just published a paper for our first nine patients; a true breakthrough. This was a patient group that we used to obtain enough data to apply for a CIHR grant. We were asked to carry out a pilot study to see if the idea would work in real life. In our initial paper which just got published last week in a very prestigious journal called, IFAR, or the International Forum of Allergy and Rhinology in the US, our trial basically showed that in our first few patients that got just the SNOT transplant actually did better than patients who got other therapies such as antimicrobial photodynamic therapy followed by the transplant, or antimicrobial photodynamic therapy on its own. Antimicrobial photodynamic therapy is another method of sterilizing the sinuses where we shine a blue light of 672 nanometers into the sinuses. It is supposed to kill 99.9% of microbes within the sinus. However, this method was not superior to the transplant by itself.

Our initial thought was that if we sterilize the sinus with the blue light to start with, and then place a healthy microbiome in it, those patients would possibly do the best. But to our surprise, those patients didn't do the best. The patients who did the best out of the entire group of nine patients were the three patients who just got the SNOT transplant and nothing else. This data was submitted to Health Canada and to the granting agency CIHR. The conclusion and final decision was that we should likely do a full and extended study on a group of recalcitrant patients with just the transplant and compare them to a similar group who would get a placebo implant.

We decided on 40 patients with a transplant by itself and 40 patients with the placebo by itself and compare the results. To date, we have completed our first 40 patients, so that 20 have had a SNOT transplant and 20 have had a placebo. We are currently carrying out an interim analysis to see what the effect is of the study, if any. This is a well done study with two PhD students and several clinical research fellows over several years. It's a massive team that's been running the show. There are several surgeons involved and two PI's (Principal Investigators), one is a surgeon, that's myself, and a PhD scientist Amee Manges from the lab at UBC.

The team is very dedicated to doing this in the best possible manner with all the checks and balances in place. We have received a CIHR grant for over half a million dollars to do this study properly. It is a double-blind placebo-controlled study, which means that the investigators and the patients do not know what they have received. This is the largest double blinded placebo-controlled trial done anywhere for SNOT transplants, and this is the first time that this has been done in so much detail, for example, we are looking at the metagenomics of the bacteria ie. we are identifying in detail the bacteria present in the sick sinuses, in the donor mucus and in the recipient patients over a period of 6 months to see if the bacteria change over time. We will be the first centre in the world to publish such detailed data.

We are also doing several offshoot studies, ie. studying whether microbial transplants can be properly persevered/stored and if so for how long. Can we end up building a SNOT bank from which we could extract healthy microbiome when needed? We are also trying to figure out what part of the transplant actually works ie. is it the bacteria or the supernatant or both? The donors are all healthy individuals who may or may not be related to the patient. The donor is heavily screened to ensure there is not a chance that they could pass on any viruses or diseases to the recipient.

During the course of our study, we are hoping for some breakthrough findings. In our first nine patients, we had three patients that had disease in their sinuses for over 20 years that completely cleared up. We were very impressed at how well they did. This is a study that's been in the making for over 20 years and it's finally coming to fruition. We are all very excited at the St. Paul's Sinus Center and UBC to have this finally come to fruition. Hopefully we'll have an 80 patient, double blinded, placebo-controlled trial published within the next year or two.

Presenter: Dr. Amin Javer, Otolaryngologist, Vancouver, BC

Local Practitioners: Otolaryngologist