Clinical Trial: Treatment of IBS with diarrhoea – titrated ondansetron (TRITON)

I was never diagnosed with Irritable Bowel Syndrome (IBS) but sometimes I feel like I now have it.  I know many others feel the same way.  But when I look at the alternatives, I can’t help thinking it’s a small price to pay given that one of them might be a slow degrading quality of life until shuffling off  this mortal coil. If I had the choice again, I would still take the surgery.

Before the article continues, let me be clear – I’m not suggesting this is a potential treatment for NET patients with post abdominal surgery side effects or side effects of any other treatment, nor am I suggesting it’s a potential treatment for those with carcinoid syndrome diarrhea.  I publish it because there is a connection to serotonin and it may be a useful read for the more curious amongst us. In fact, since publishing I’ve been contacted by several people telling me they are aware of the drug having been treated with it for nausea.

I once wrote about IBS in an article entitled “Were you irritated by your misdiagnosis” (click the link to read).  This was written after I completed an online IBS course.  I wrote the article in a balanced way in an effort to explain why many patients are misdiagnosed with IBS in the lead up to the correct diagnosis some time later.  This is an issue with other conditions, not just NETs.  It was also designed to capture IBS readers and offer them a chance to review their diagnosis to ensure there wasn’t anything else they might try to double-check (markers and scans mainly).

A new drug on trial for IBS

Given the connection between NETs and IBS, I was really interested to see this in a UK national newspaper and I subsequently researched for some formal papers to back up the headline.  What I found most interesting was the suggestion that a drug designed to inhibit serotonin was involved (…… but read on rather than get too excited).

Diarrhea – the IBS and NET Effect

Diarrhea is a big feature of IBS although there are several types including diarrhea mainly, constipation mainly and a mixed of both – you can read more in my IBS article linked above.   Diarrhea is also a big feature of several of the NET Syndromes, in particular Carcinoid Syndrome.  It is known that the cause of carcinoid syndrome diarrhea is the oversecretion of serotonin.  This makes is quite distinct from other reasons for diarrhea, including but not limited to side effects of intestinal surgery (as one example).

Clinical Trial: Treatment of IBS with diarrhoea – titrated ondansetron (TRITON)

What is ‘ondansetron’. It’s actually a powerful anti-sickness drug given to cancer patients and some of you may recognise it as ZOFRON.  Interestingly it’s a serotonin receptor (5-HT3) antagonist (5HT3-RA) for antineoplastic chemotherapy-induced nausea and vomiting. Ondansetron is a drug which blocks the 5-HT receptor, which is used to treat nausea and sickness, and has an excellent safety record.  Other 5HT3-RAs include Tropisetron, Granisetron, Dolasetron, Palonosetron, Ramosetron (the group of drugs in the class known as 5HT3-RAs are known a ‘setrons’).

It is being offered to those with irritable bowel syndrome (IBS), helping to ease the most embarrassing and painful symptoms of the condition.  According to the Daily Mail, if the trial is successful, it could throw open the doors to the first targeted treatment for the millions of IBS patients with bloating, abdominal discomfort and urgent bowel movements. Two people on the trial are featured in the newspaper article reporting good outcomes.

Information on the Trial.  Researchers are hoping to recruit 400 volunteers in the UK aged over 18 who have IBS to take part in the 12-week study.  You can read more about the trial in the reference documents below.

Read more here:

1. The Daily Mail article. Click here.
2. Trial Sponsor site.  Click here.
3. Clincial Trial Document.  Click here.

Would this work for carcinoid syndrome diarrhea?

I guess many of you will now be thinking that but I advise not to get too excited as things are never that straightforward.  However, if I was a pharmaceutical involved in NET research, I would certainly be watching this trial carefully.  None of us know the interaction between NETs, NET treatments and titrated ondansetron and its mechanism of action. It may be more directed at brain and central nervous serotonin rather than gut serotonin which is mainly the issue with carcinoid syndrome diarrhea, i.e. it may not work in the same way and/or have the same effect as other approved NET drugs such as somatostatin analogues (Octreotide/Lanreotide) and tryptophan 5-hydroxylase (TPH) inhibitors such as XERMELO.

Still, it’s an exciting trial.

I will keep this article live for any developments.  Finally please note this is not in any way medical advice and not a recommendation to try these drugs to control your diarrhea.

Thanks for reading

Ronny

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