Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study - 2020 - Rekeland, Mella, Fluge et al

There are no other great options if you have bad or progressive MECFS though are there ? Atleast it is a treatment study and perhaps with the potential of increased European funding, it’s something they can tap into, or else get a 50/50 split patient/ state funding as they did for rituximab.

just linking here to another treatment exploration study given there arent many I’m aware of
http://simmaronresearch.com/2019/04/help-simmaron-amplify-therapies-for-m-e/

 

They are comparing a group of 12 with the alleles with a group of 28 without. The numbers are just much too small to be reliable and meaningful. My bet is it is just random, it means nothing.

 

It seems that mild ME was reason for exclusion
Inclusion criteria were: a diagnosis of ME/CFS according to the Canadian criteria (4); age 18–66 years; disease duration more than 2 years; and disease severity mild-to-moderate, moderate, moderate-to-severe, or severe. Patients with either mild or very severe disease (completely bedbound and in need of help for all basic activities of daily living) were not included.

As far as I understand 3.200 steps pr. day was mean, not for everyone? So there might have been a few patients able to go for walks and thus pulling that number upwards for the rest. It's also interesting that they write:
“Steps per 24 hours” is an objective measure, but not a perfect way to validate symptom improvement because individual patients will use their improved energy for different purposes. Some will walk, while some will prefer to read or increase the time for social activity.

 

Ok so they were "mild-to-moderate" not mild. The subgroup of responders was doing 3,600 steps per day on average before the treatment. That's quite a lot considering that half of the general population walks less than that:

https://www.theguardian.com/society...-of-adults-walk-less-than-a-mile-a-day-survey

 

That might vary from country to country. I think the average in Norway is about 5 000 steps.

 

I dont disagree that we have to look at the results with great caution, but I dont think it is very likely that the study had so many patients that were undergoing a slow gradual spontaneous improvement. All research (not with canadia criteria mind u) suggests that around 5 percent undergoes spontaneous recovery, however, its possible they all are experiencing a placebo response (as seen in rtx-trials). Thats why we need a phase 3 to draw any conclusions

 

Has Ron Davis' team tried out Cyclophosphamide with the Nanoneedle test?

 

We dont know what the placebo rate will be next time though, it seemed unusually high for me

 

There are some of you that points out that cyclo should not be allowed by experimental doctors until a phase 3 study is performed with positive results, and the researches do too. I understand the possible risks.

Yet I disagree. I tried rituximab by the experimental doctor in Sandnes, and was glad that I wasn’t in the study. Then I had felt more obliged to adhere to the protocol and do all doses. I did four doses, and on the fourth I deviated from the protocol, having it 1,5 month late.
That was because I found myself an early responder, but the response vanished with the third dose. Then I decided I wouldn’t have more doses until the improvement came back, that was ok by the doc, I had to wait four months for that. Then I went for my fourth dose, got sick again, and never saw that improvement again. Of course I didn’t want more doses. But if I was in the study I would not feel free to just drop out. And possibly get worse by the remaining doses. That is what I think would have happened.

So, if cyclo was available for “buying” I would have bought one dose and see how that goes, and decide further after that.
But I also see the problems, yes.

 

But these patients were not experiencing spontaneous recovery. They were mildly improved at best and as Trish pointed out the results were comparable to the placebo arm of the RTX trial. Their SF-36 score was still terrible compared to the median score in the general population.

I strongly disagree that we need a phase 3 trial of this toxic drug that showed essentially null result in an unblinded study. I would hope that no one would fund such a study and that any ethics committee looking at such a proposal would put a stop to it before more people were harmed. Enough people have been harmed by RTX already, financially and otherwise.

 

There is probably a big auto-immune component in subgroups of ME patients. Since ME still is not a disease. After 5 years of having an ME diagnosis I got diagnosed with Primary Sjogren (no sicca symptoms). Cyclofosfamide is on the list of treatments for primary sjogren... Makes sense certain patients got better in this "ME" study.

 

@Sid

I respectfully disagree with your assessment. There was not a null result in this study. "Fatigue score and other outcome variables showed significant improvements compared to baseline." "At baseline, only two of the responders had part-time work participation. During follow-up, at least nine out of 22 responders returned to either part-time of full-time work or studies." This seems to be a good thing, no? There were side effects/adverse events, but this is expected in all drug trials.

Who was physically harmed by rituximab? I don't know of people who were.

Again a lot of this boils down to an unhelpful belief on these fora that the treatment/cure for ME/CFS will be very benign, like taking a vitamin pill. Almost all of the medications for chronic diseases have serious/dreadful side effects. So I vigorously support a Phase III trial.

 

I think the step count should be taken with a grain of salt, and referred to as an activity measure. That's okay if you are comparing like with like. The paper describes using SenseWear activity armband. So if you have sufficient arm movement it may count as steps.

I've no idea which version of armband they used but this papers conclusions should be taken into account.
Validity of the SenseWear armband step count measure during controlled and free-living conditions

 

Anecdotally I'm aware of a number of people who were. Given that they haven't gone public with their stories I won't reveal names, which I appreciate then means that I can't provide you with any proof, other than the fact that I believe there were. Additionally, 26% of patients (20 in total) in the stage 3 Ritux trial had adverse effects - can't access the full paper at the moment to look at what they where but that is the figure reported in the abstract.

I have seen no evidence of such a belief here. With almost every treatment there will always be a cost to go along with the benefit, and currently there is insufficient evidence of potential benefit that outweighs the potential cost to convince me to take cyclo, or to be comfortable in supporting people to try this outside of a trial.

I'm in two minds about a stage 3 trial of cyclo - the results from this trial seem to mirror the results of the stage 2 ritux trial too closely for my liking, which puts me off, but we might need a stage 3 trial to provide us with a, hopefully, definitive answer.

 

OMF in their new may fundraiser info say they plan to do two pilot treatment trials of kynurenine & mestonin. I think that the Later i am not impressed particular will certainly please a lot of people. Jen brea had help from it and a science graduate on Twitter has gone on it following a CPET test with abnormal results, and found it helpful I believe. So I’m delighted there are a few therapies being explored.

if this is considered too off topic please move but I thought that it Tied in with theme of current and proposed treatment trials.

 

I feel the same way. I'm hoping there might be a few more papers to come, perhaps trying to detect certain antibodies such as the peptide array method of this paper. Maybe they can identify something common among responders.
Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis Using a Random Peptide Microarray Differentiates Cases from Controls with High Specificity and Sensitivity.

I think Bateman Horne had promising findings on a similar peptide array study from a first cohort that they were running a second cohort through. But not heard anything on that for 18 months or more.......

 

That's interesting, I've read that people with Sjogren's have an increased risk of developing non-hodgkin's lymphoma. I believe that they first noticed that cyclophosphamide was having an effect when they treated patients for non-hodgkin's who also had ME and found that the ME improved after the treatment (this was certainly the case with rituximab but I think also the case with cyclophosphamide?) Might it be that those patients actually had undiagnosed Sjogren's prior to developing non-hodgkin's? Maybe in the trial it is helping the subgroup who actually have Sjorgren's?

nb/ - I might also be completely wrong about this, it's all a bit over my head, do correct me if this is irrelevant/wrong!

 

Yes 5 percent has been the mean in the studies looked at (not after strict criteria,), the systematic review being one of them. Im not claiming it is correct or anything but I know for a fact its not higher, hence why i used it for the sake of argument here.