The Comeback Study: fecal microbiota transplant for ME/CFS

Some details are now know. I'm not happy about Chalder fatigue scale being used as primary outcome.

https://clinicaltrials.gov/ct2/show/NCT03691987

 

In theory it looks an interesting study, but in practice I agree with @strategist that the Chalder Scale is at best very problematic.

The recent Vink and Vink-Niese paper, though considering the studies used in the Cochrane GET review, has a very helpful section on the problems with the Chalder Scale (see http://journals.sagepub.com/doi/full/10.1177/2055102918805187 )

 

A null result in this study may not rule out a disturbed gut flora being implicated in the symptoms of ME. If the fecal transplant does not restore the microbiota balance are there other factors involved in perpetuating the imbalance?

On a totally unscientific and anecdotal level, when I have tried various approaches to rebalancing my gut flora (probiotics, capsules purportedly effecting fecal transplants, natural yogurt, etc) they have only seemed subjectively helpful when accompanied by a modification of my diet. However for me eating well is only consistent when my health is relatively good, so sorting cause and effect is difficult. Does eating well and having a balanced gut flora make me feel better, or is it only possible when I already feel better?

 

I believe this study was talked about at the 2018 IiME conference, thread here https://www.s4me.info/threads/fecal-transplants-in-me-cfs.4409/

 

Anyway, I am very curious about the results, considering case reports like this:

http://www.scirp.org/journal/PaperInformation.aspx?paperID=75761

 

In the reported case study, is it not internally inconsistent to refer to a condition as a 'functional disorder' at the same time as believing FMT provides a 'good medical therapeutic intervention'.

 

There is also the role of metabolites (build up of histamine in particular) that may be the root cause of the IBS rather than anything microbiological.

If this is the case, faecal transplants could have zero effect since the reason for the problem in the first place is unrelated. And that’s despite the use of a nonsense fatigue scale that doesn’t measure anything.

Also anecdotal: I had constant IBS before I was pacing effectively. It now only flares as part of PEM or if I’ve overeaten (too many calories in one sitting) and is frequently accompanied by itchy skin and hives. My flare can now quickly resolve itself within a couple of days, also indicating it’s unlikely to be a major disruption of gut flora to blame. Of course there could be a number of different factors at play including microbiological, but I doubt anyone interested in gut flora would be interested in exploring the biochemistry angle.

 

Canada Criteria (2011)? If they mean the ICC (2011), then they should make clear that this is a study into ME instead of CFS/ME (but maybe they just got the date wrong and they mean the CCC, (2003)).

Also: I would have selected a subgroup of ME/CFS patients with a higher probability for the treatment to work (for example in patients with comorbid IBS). It seems more feasible to expand a positive result to other ME/CFS subgroups, than to immidealily start with unselected ME/CFS patients. Heterogeneity might mask positive results for a subgroup, and it will be hard to attract funding after an initial negative result.

 

As others have already said, this might be very promising ... but why oh why can it not include objective outcome measures for reliably establishing if ME/CFS symptoms are truly resolved? I mean, why not?

It's good the groups are being effectively blinded to treatment. Hopefully full blinding, including trial staff not just participants. But given objective outcomes can so readily be measured, and have such high scientific value, I don't understand their problem.

Maybe it depends whether they think the dysbiotic gut flora is being caused by unhelpful beliefs?

For me this study is interesting because my gut feeling (deliberate pun ) is that gut issues and ME may have some correlation for at least a sub-group of ME patients. My wife's family has a history of having to be careful about what they eat, as well as auto-immune conditions. From what I read, this is far from unusual.

 

So, do they actually destroy the gut's microbiome prior to FMT, or do they just empty the gut? This is kind of glossed over in what I've read and I'm not certain that they are the same thing.

FMT can frequently cure C. difficile infection, but C. diff is not normally present in the gut (although some people who have it are asymptomatic).

I'm just wondering if FMT can restore a healthy microbiome balance to the gut, especially if the presumably dysfunctional balance is not entirely eliminated first.

Or is the theory that some unknown bacteria needs to be eliminated, as in the case of C. difficile?

 

Or possibly it is some unknown bacteria that needs to be replenished because it was wiped out due to infection or antibiotic use.

 

Unfortunately, since they haven’t mapped out what healthy looks like at a species level yet, no one knows what they are aiming for.

The whole microbiome disruption idea is just a very loose theory at the moment and rife with very poor meaningless studies as a result.

 

I experienced a permanent change in microbiome after an infection. Not the intestine though. I am pretty certain it was the pessary antibiotic that was used at that time. I was never the same again.

This was back in the 80s. I tried to get answers from doctors at the time but realised they knew nothing. So you can imagine after all these years hearing the microbiome discussed as an area of research now is exciting to me but also upsets me in that I have suffered a long time without answers. Then I got ME years later via a flu.

The question for me is what is the reaction that takes place between antibiotic and microbiome causing permanent change in composition, how does it happen, what is the process and further downstream effects of sudden permanent change.

I understand no one knows much about the microbiome but for me I have been waiting a long long time for microbiome research. I hope we get to understand it eventually and continue researching it.

 

The Norwegian research project on faecal transplantation and ME, The Comeback Study, are still recruiting. They are cooperating with prof. Maureen Hanson.
Here's an introduction to the study in English at the website Smart Patients - The Comeback Study

 

I've been told that they will not use the Chalder fatigue scale.

 

My onset was similar. From what I can tell, the current position of the medical industry is one of aggressive denial about the sometimes devastating and permanent alterations of the microbiome caused by (often needlessly) prescribed antibiotics, especially when given in infancy before a robust ecosystem has been established. And when the studies are shown to them, the answer turns to "well so what if antibiotics wipe out beneficial as well as harmful microbes, you don't need those bacteria anyway, they have no effect on human health". Yes, perfectly logical to think that that microorganisms our immune and metabolic systems co-evolved with for millions of years would have no effect whatsoever on our bodies.

 

Hi @Sid I'm about to take a break from the forum for a while. I'm so glad I caught your post.

I often think about the MEs with gut problems and whether they experienced the same altered composition in microbiome which made them vulnerable to getting ME, like me. My changes were vaginally after an infection so it was easier for me to notice a sudden and permanent change.

People with gut changes can't see their flora as easily as I can with the vaginal flora so not able to pinpoint as easily. I get pain only with pressure, so sex was painful for me.

I just hope someone out there might be able to see some connections and possibilities as to what may be going on. I think the microbiome changes (in some MEs) are kicking off downstream pathway alterations.

I wonder how many there are of us with the microbiome lead up to ME.

 

My son had occasional stomach problems when he was younger at 7, 8 and 9 years of age. Mainly in the evenings where he would be screaming in agony and we were told by various doctors that he needed more vegetables. I assume they thought he was somewhat constipated although they never specifically said as much. However, we have always had a relatively healthy diet so the suggestion seemed futile to me. Perhaps this was a precursor to the onset of CFS - an imbalance in his micro-biome. After the age of 10/11 he started to voluntarily give up a lot of processed foods e.g. processed meat, gelatine, ketchup etc This was followed by a year or so of headaches before the onset of ME/CFS at the age of 12. My daughter also had stomach problems at a similar age so I wonder whether ME/CFS is mapped out in her future?

 

Update from The Comeback Study, a study on ME and faecal transplantation.

This was one of 4 research projects that received allocation via the Norwegian Research Council's pilot project on user identified research. The study is taking place at Harstad in Norway.

It says (hastily translated by me):
Hi. Apologies for this late update, but here is a status on the trial per now. We've run a pilot study and the next step is to begin inclusion of participants for the main trial. The reason behind this has taken longer than expected are different factors concerning selection of donor and to build up a sufficient number of donor transplant. There is very strict regulation concerning donor selection, which is time consuming. The process is still ongoing, but it looks as if we're able to include participants starting in May. The inclusion process will take a few months (with a summer break), so some might not be contacted until the autumn. We'll publish a new status on this page once all participants are included. If anyone have questions you can send them as PM, and they will be answered as soon as possible. As inclusion is ongoing, people can still get in touch if they want to take part in the trial. Please do that by sending a PM with contact information (address, mail and telephone number). Please don't send sensitive information. Sorry for the wait and thank you for your patience.

 

I'm a bit worried that they've decided to use enema instead of colonoscope for the transplant. Somehow this doesn't seem to be an optimal way to deliver the bacteria to the whole colon.