# New study finds Alosetron (Lotronex) no better than placebo for IBS



## Guest (Aug 3, 2000)

Aliment Pharmacol Ther 2000 Jul;14(7):869-78 Effects of alosetron on gastrointestinal transit time and rectal sensation in patients with irritable bowel syndrome. Thumshirn M, Coulie B, Camilleri M, Zinsmeister AR, Burton DD, Van **** C Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA; Section of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA.BACKGROUND: Alosetron, a 5-HT3-receptor antagonist, relieves abdominal pain and improves bowel function in non-constipated, female patients with irritable bowel syndrome. 5-HT3 antagonists delay colonic transit, increase colonic compliance, and increase small intestinal water absorption. AIM: To evaluate the effects of alosetron on gastrointestinal and colonic transit, rectal compliance and rectal sensation in irritable bowel syndrome. METHODS: A double-blind, placebo-controlled, two-dose study of alosetron was performed in 25 non-constipated irritable bowel syndrome patients, with paired studies before and after 4 weeks of treatment with placebo (n=5), 1 mg alosetron (n=10) or 4 mg (n=10) alosetron b.d. Gastrointestinal and colonic transit were measured by scintigraphy. Rectal compliance and sensation were assessed by rectal balloon distention with a barostat. RESULTS: There was a trend (P=0.06) for 1 mg alosetron to increase rectal compliance (median pressure at half maximum volume 11 mmHg after alosetron vs. 15.6 mmHg before alosetron). The 1 mg b.d. alosetron dose non-significantly retarded proximal colonic transit. Alosetron and placebo reduced sensory scores relative to baseline values; none of the changes induced by alosetron was significant relative to placebo. CONCLUSIONS: Alosetron had no significant effect on gastrointestinal transit or rectal sensory and motor mechanisms in non-constipated irritable bowel syndrome patients in this study. Alosetron's effects on colonic sensorimotor function and central sensory mechanisms deserve further evaluation.--------------------------------------------The sample size was small, and the trend towards significance (P=0.06)may have reached significance with a larger subject population. However, this is not the first study to report that Lotronex was no better than placebo in reducing IBS symptoms. As the study authors note, stay tuned...


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## Guest (Aug 3, 2000)

Maybe I'm misreading or over-reacting to this - but it certainly seems VERY SIGNIFICANT, especially considering that the study apparently has the "Mayo Clinic" name behind it.Granted, the sample size was small, but the language of the study is pretty dramatic: "...non-significantly retarded proximal colonic transit..." and "...none of the changes induced by alosetron was significant relative to placebo...". Those are statements that would seem to poke a finger in Glaxo's eye. Yikes!!Anybody else see this as an issue, or am I just reading too much into it??BJP.S. Of course, there is always the circumstance of those for which alosetron seems to work. In those cases, it works, so who cares if it's a "placebo" effect. This study just seems to contradict what Glaxo says.


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## Rose (Mar 25, 1999)

I'm a C type and don't take Lotronex and probably never will, but this study shocks me. Looking at this board alone, it seems so many people have been helped by this drug, it is hard to believe that it is no better than a placebo. Personally, I know of a person taking it, who swears it works miracles for her. She does not take it everyday, but if she wakes up with "D" in the morning, after a few trips, she pops (1) pill and she says it stops the "D" dead in its tracks.------------------"Remember To Stop and Smell the Roses"Rose (C-type)


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## Clancy Garner (Apr 5, 2000)

Well... if it is the placebo effect I love it!! It has made a VAST change in my bathroom habits.


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## Bud (May 16, 2000)

Guy, your post is good and has significance. I just want to add that anyone reading the results of the study shouldnï¿½t question the possibility that lotronex can help them. My wifeï¿½s symptoms are severe abdominal pain and ï¿½Dï¿½. She started taking lotronex about three weeks ago and there was improvement within the first 24 hours and, in general, her quality of life has improved every since. In fact, this is the ï¿½FIRSTï¿½ time since this whole IBS nightmare started (1 Year) that she doesnï¿½t have diarrhea. Point being is that this study shouldnï¿½t act as a deterrent for anyone considering lotronex. Just like the diversified symptoms of IBS, the effects of different meds on different people will vary significantly.Thanks!


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## Guest (Aug 4, 2000)

Bob,This same Mayo Clinic group has published work establishing significant improvement of IBS-D symptoms in females (but not males). See my other post on this topic. Rose,The placebo effect can be quite large in some studies. For example, one Lotronex study which did find a significantly higher(41%) response rate to Lotronex relative to placebo nevertheless found that 29% of the placebo group also reported improvement in their IBS symptoms.


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## eric (Jul 8, 1999)

Guy, it just goes to show you the power of the mind, especially in IBS. This is an interesting thread and I don't even think Glaxo knows for sure as they are still testing and keeping an eye on the drug.I am sticking with the hypnotherapy personally, although if Lotronex helps you it helps you. I think other new ones will be out in the future.------------------ http://www.ibshealth.com/


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## flux (Dec 13, 1998)

> quote: but it certainly seems VERY SIGNIFICANT, especially considering that the study apparently has the "Mayo Clinic" name behind it.


That doesn't necessarily mean a lot. Not all of what they publish at least in this area is that great.


> quote:but the language of the study is pretty dramatic: "...non-significantly retarded...


It's statistical language, so I wouldn't interpret it as "dramatic." It just means that the effects could be due to chance and not the drug.


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## Guest (Aug 4, 2000)

A couple of observations about this thread and its contents...Eric, I agree with you - this has promise to become an interesting discussion.Rose, Clancy, and Bud - I agree with the notion that if it helps, it helps, and who cares "why". Plus, Bud, you make a very good point that studies like these shouldn't necessarily deter individuals from considering the drug's possibilities for them.Now for flux...I recall a thread not too long ago where you carried on an extended discussion with Mike NoLomotil about the virtues of sources and "reliable" studies. Your comment that the Mayo Clinic "name" on a study "doesn't necessarily mean a lot" brings that previous discussion to mind. I'm not rendering a judgement on your opinion about that, but I would like to know on what basis you consider this source "Not...that great".Secondly, notwithstanding "statistical language", a conclusion that "the effects may be due to chance and not the drug" does seem to be at odds with what Glaxo claims. My choice of the word "dramatic" may have been over-reaching, but I still think that the conclusion is of some note.This whole thing about this study brings in to question the moving target that studies present. I mean, one decade studies claim to show a connection between one thing or another and cancer, and the next decade studies reverse that view and claim it's OK to have coffee with caffein in it, or eggs with cholesterol, or use your cell phone without fear of brain cancer (with the new caveat that all must be done in moderation). You have to admit, it's a moving target a lot of the times. That's why I raise an eyebrow when I hear someone reference a study as their basis for an argument. Studies are often useful, but not as a stand-alone basis for a decision.BJP.S. Guy, I did see your other post on this topic, and made a reply to it. And I agree that more studies need to be done on this (so that the issue will become more confused?? ;-).


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## JeanG (Oct 20, 1999)

Thanks, Guy!







JeanG


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## sickntired (Jan 6, 2005)

Very interesting. Thanks so much for bringing this info to us. I think that lotronex is so new that no one knows a whole lot about it yet. I am always glad to know that people are still looking into it and doing tests. Even if the results aren't favorable







It is a relief to know that it is still under the microscope.


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## Guest (Aug 5, 2000)

Bob,I agree that single studies, by themselves, usually do not mean very much (though there are occasional exceptions). However, when studies come out which directly challenge tradtional viewpoints with good, solid data, they are useful since they stimulate others to take a second look. With only seven published studies of Lotronex in humans, some conflicting, it's clear that many more studies need to be done. For example, will a larger dose of Lotronex work for men? We don't know, but I'm sure someone (Glaxo)? will look at this. I'm speculating here, but my suspicion is that part of the reason the FDA approved Lotronex is that it appeared to provide relief to some people who had not found relief with any other treatment. Since IBS is more common in women, making a IBS drug available, even if it worked only in women, was likely seen as a significant advance. Lotronex is the first of what will probably be a wave of serotonin antagonist/agonist drugs for IBS D/C, and more potent drugs may be part of that wave; Cilansetron, for example, has been reported to be much more potent than Alosetron (Lotronex). For those men who do not find relief with Lotronex, Mirtazapine(Remeron) might be worth a try. This drug also antagonizes the 5HT-3 receptor, as Lotronex does, but works equally well in men.But, of course, I'm biased in suggesting that...


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## Guest (Aug 5, 2000)

I would like to meet the poor people that participated in this study. Can you imagine?Oh my.


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## flux (Dec 13, 1998)

> quote: but I would like to know on what basis you consider this source "Not...that great".


Well, with regard to colonic manometry, they are still using older methods of manometry, namely the non-ambulatory water-perfused manometry, which requires subjects to be confined to a bed for several hours while they are tubed and they are only collecting from distal parts of the colon. These tests are probably somewhat stressful on subjects. In addition, the water-perfused manometry may not be as accurate as the newer electronic transducers. In additon, the colon has to be flushed before the study is done and this non-natural state of the colon may affect how it behaves. Finally, at least some of their data has been oddly filtered, so what they are showing is not the raw data and that makes it difficult to compare to other data.One's judgement plays a role here. For example, I am making the value judgement that because of the reasons I have outlined above, I am sometimes somewhat skeptical of their data. So I may be inclined to judge their data in a negative light whereas I might judge other data-produced in another way-in a better light. It's possible, however, for that judgement although reasonable and rational to be outright wrong.


> quote:You have to admit, it's a moving target a lot of the times. That's why I raise an eyebrow when I hear someone reference a study as their basis for an argument. Studies are often useful, but not as a stand-alone basis for a decision.


Learning how the world works is not always an easy task. When an hypothesis is chosen to be studied, researchers face many hurdles to getting good, valid data. A sample must be chosen that is random and representative. In IBS, for example, this is difficult because there is no definitive way to identify it. Researchers must rely on the symptomatic definition in Rome II. If this definition is inexact, it can lead a contaminated population. Also, for example, IBS studies are often conducted in big cities and that could lead to a biased population of urban dwellers. Researchers must also rely on the biased subjective reports of patients whose main interest is in getting better and not necessarily the interest of science (and researchers may similarly be biased in looking for good data they can writeup). This is just sampling of issues that can spoil the accuracy and precision of the conclusions.


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## Guest (Aug 5, 2000)

flux,Thanks very much for the considered and "reasonable" response. Well put...BJ


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## Guest (Aug 5, 2000)

25 patients is WAY too small of a group to make definative conclusions with. Also, I am not clear on this, but I think the primary endpoint (what they were studying) was pain perception at the end of colon. So in 25 people, only some of them could decipher differences in pain with a balloon inflated in the rectum? If lotronex works on about 60% of people who use, yahoo! (no infrigement of trademark intended)In regards to "placebo effect", in the big study the FDA used to approve the drug, there was a sharp decline with the people who had relief when the drug was switched to placebo in the last 4 weeks of the study. Which meands their guts knew they went off the drug, even if their heads didn't! I dunno, if the stuff helps, God bless 'ya!


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