Protocol Faecal microbiota transplantation (FMT) in Norwegian outpatients with mild to severe ME/CFS: protocol (...), 2024, Skjevling et al. Comeback Study

Study details were amended in February this year. History of changes can be seen here, https://clinicaltrials.gov/ct2/history/NCT03691987?A=1&B=2&C=merged#StudyPageTop, the headline change is, as mentioned above, they have removed Chalder Fatigue Scale.

From IiME newsletter

 

This just shows how ridiculous the BPS approach is. A trial of CBT for MS resulted in fatigued MS patients REPORTING less fatigue than healthy controls. Honestly

 

That combined with the positive self-reported results from the Rituximab trial makes it clear that subjective outcomes should be entirely eliminated as primary outcomes. Secondary? Sure, indicative of something possible, at best. But as primary outcomes? Might as well be doing particle physics using a hot-hotter-very hot-maximal hotness temperature scale.

I'm fine with secondary subjective outcomes. They mean almost nothing but you can still get some information out of them, mostly in how they align with objective primary outcomes. But there has to be a way to move for the complete elimination of subjective primary outcomes in medical research, it's completely corrupting the value of all medical research by making comparisons that may as well be apples to Roentgens.

 

Update from the Comeback Study, a trial on ME and fecal transplantation at the University Hospital of North Norway

(hastily translated by me)

Hi. A small update from the research group behind the Comeback Study. First of all we'd like to say thank you for the allocation from the Norwegian ME Association to the study. This is a great help in the further work with the study, both when it comes to progression and to make the most of the potential in the material which will be collected. As of today the study has included about 1/3 of its participants. This means there's still a chance to report your interest in participating in the study. We ask that you only give your contact info (telephone number, e-mail address and mail address) and no sensitive information. When it comes to the recruiting process there are several matters that must be taken into consideration when it comes to financial aspects for the project and feasibility for the participants, in addition to some given criteria for participation. We try to give direct response to everyone who are interested in joining, but ask for your understanding that this may take some time. If you don't hear from us and are still interested in participation, please send a new notice. Regards, the research group

 

A medical newspaper has an article about the ongoing clinical trial on fecal transplantation and ME; The Comeback Study.

No revealings regarding results, but researcher Linn Skjevling says it's been challenging for ME patients to travel to them for treatment, and that patients have put in a lot of work in order to make it happen.

Dagens Medisin: Håper på svar om link mellom tarmflora og sykdomsaktivitet
google translation: Hoping for answers about the link between gut flora and disease activity

quote:
- There has been more focus on this with intestinal flora and various diseases in the last ten years. There has been much more information about this connection that many have probably heard about and thus they are excited about whether it can have an effect.

According to Skjevling, what makes the study exciting is that they start at the opposite end.

- Studies have been carried out in other countries that look at the intestinal flora in those who have ME compared with healthy controls, while we have looked at whether you get healthier by adding new intestinal flora.

 

Looking forward to the results. Can we please have a positive trial, but I'm preparing myself for the worst...

 

I know of someone who got a FMT and that landed them in ICU with sepsis, so I am concerned about this trial.

 

Yikes, but then again. Any treatment can have dire outcomes for some people. Let's hope it's not the case for the majority.

 

I think the gut and other areas of microbiome problems have been caused by an immune reaction and it has seized the microbiota changing it permanently. It can't return to the original composition. I can't see how transplant will turn things around except for very temporarily. The microbiome will keep returning to the faulty composition because the programme has been changed permanently by the immune system. But in saying that I hope they will find leads.

I know immunology has MAIT states of muscoa: For those of us with altered microbiome I wonder if we have got a type of this without other of the usual symptoms that go with reactive arthritis.

 

Received 01 March 2023, accepted 11 March 2024, published June 10, 2024.

Faecal microbiota transplantation FMT in Norwegian outpatients with mild to severe myalgic encephalomyelitis/chronic fatigue syndrome ME/CFS: protocol for a 12-month randomised double-blind placebo-controlled trial
Linn Skjevling; Rasmus Goll; Hege Marie Hanssen; Peter Holger Johnsen

INTRODUCTION
The observed alteration of the intestinal microbiota in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the effect of transferring a healthy gut flora from a faecal donor using a faecal microbiota transplantation (FMT) will be explored in this trial.

METHODS AND ANALYSIS
This is a protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial, with 12 months follow-up. 80 participants will be included and randomised (1:1:2) to either donor FMT (from two different donors) or placebo (autologous FMT).

Participants will be included by the International Clinical Criteria for ME/CFS. The clinical measures of ME/CFS and disease activity include Modified DePaul Questionnaire, Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Health Survey (SF-36), ROMA IV criteria, Food Frequency Questionnaire, Repeatable Battery for the Assessment of Neuropsychological Status, heart rate variability testing and reports on the use of antibiotics and food supplements, as well as biobanking of blood, urine and faeces.

The primary endpoint is proportion with treatment success in FSS score in donor versus autologous FMT group 3 months after treatment. Treatment success is defined as an FSS improvement of more than 1.2 points from baseline at 3 months after treatment. Adverse events will be registered throughout the study.

ETHICS AND DISSEMINATION
The Regional Committee for Medical Research Ethics Northern Norway has approved the study. The study has commenced in May 2019.

Findings will be disseminated in international peer-reviewed journal(s), submitted to relevant conferences, and trial participants will be informed via phone calls.

TRIAL REGISTRATION
NCT03691987.


Link | PDF (BMJ Open) [Open Access]

 

Full title:
Faecal microbiota transplantation (FMT) in Norwegian outpatients with mild to severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): protocol for a 12-month randomised double-blind placebo-controlled trial

Abstract

Introduction The observed alteration of the intestinal microbiota in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the effect of transferring a healthy gut flora from a faecal donor using a faecal microbiota transplantation (FMT) will be explored in this trial.

Methods and analysis This is a protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial, with 12 months follow-up. 80 participants will be included and randomised (1:1:2) to either donor FMT (from two different donors) or placebo (autologous FMT). Participants will be included by the International Clinical Criteria for ME/CFS. The clinical measures of ME/CFS and disease activity include Modified DePaul Questionnaire, Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Health Survey (SF-36), ROMA IV criteria, Food Frequency Questionnaire, Repeatable Battery for the Assessment of Neuropsychological Status, heart rate variability testing and reports on the use of antibiotics and food supplements, as well as biobanking of blood, urine and faeces.

The primary endpoint is proportion with treatment success in FSS score in donor versus autologous FMT group 3 months after treatment. Treatment success is defined as an FSS improvement of more than 1.2 points from baseline at 3 months after treatment. Adverse events will be registered throughout the study.

Ethics and dissemination The Regional Committee for Medical Research Ethics Northern Norway has approved the study. The study has commenced in May 2019. Findings will be disseminated in international peer-reviewed journal(s), submitted to relevant conferences, and trial participants will be informed via phone calls.

Trial registration number NCT03691987.

STRENGTHS AND LIMITATIONS OF THIS STUDY

• In-depth characterisation of participants and biobanking at multiple time points will enable research on possible underlying mechanisms and mediators of an altered intestinal microbiota and might provide a future novel treatment modality.
  
  
• Whole-genome sequencing will provide information about both bacterial composition and functional potential of the microbiome in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), complementing primary and secondary endpoints elucidating the causality between an altered microbiota and ME/CFS.
  
  
• A study with a different donor chosen by the same criteria, with repeated treatments and/or another delivery method than enema (capsulated faecal microbiota transplantation, endoscopic delivery) might give a different result.
  
  
• Patients with very severe ME/CFS are not included in the study.
  
  
• Double-blind, randomised, placebo-controlled design.
  

Open access: https://bmjopen.bmj.com/content/14/6/e073275