Trial Report RESTORE ME: A RCT of Oxaloacetate for Improving Fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2024, Cash et al

I’m only well enough to scan and see if there was a longer term measure so might have missed something on that

but that is what these days I’m looking for having had experience of many things or pints in time where I feel or function a bit more short term only for that to catch up with me whether I stop or it catches up to stop me (it’s probably both as I’m pretty determined and then there’s a point where you realise you are getting worse and can’t do what you did)

I think this always used to be known given that’s surely why people warn stimulants etc don’t actually work

so I’m disappointed this isn’t much longer time points and also having some triangulation measures that ensure people aren’t kidding themselves because in some fatigue = how tired you feel / what you did to feel tired and not just whether you feel dozy or lethargic one day whether you were lucky enough to be lying around for weeks on end or had the peak time at work. And if people cut back and get tenacious about things like starting online groceries or just doing a quick tidy (knowing it will build up) or skipping x that week of getting early nights that matters vs their start point?

it’s one thing too if even if something ‘worked’ it makes you feel more alert for eg your six hours a day vs overall making you less exhausted vs both and you don’t get PEM fir doing more and you don’t crash every fortnight or months in

I don’t know how stuff like this is helpful because we can never really compare what does what even to have something as part of a combination of options to help different people if we don’t test all of these to see what it helps with what it doesn’t etc

I haven’t looked at what was covered by this ‘safety’ priority either but surely a 12month + follow up is also key here to make sure function hasn’t ended up below the start point etc (to at least give warnings or advice about it eg if it is in some but not others)

 

Had a look at the data and the group difference was 0.81 [95% confidence interval: -1.32 to 2.94], with a t-test p-value of 0.449. The cohen d effect size is 0.19 [-0.30, 0.68].

So nothing to see here unfortunately.

 

Yates's correction for continuityQuite a few patients scored a value of 0 at baseline or follow-up which seems weird given that these were the completer's analysis, so 0 doesn't indicate missing data.

The abstract writes: 'A greater proportion of subjects in the oxaloacetate group achieved a reduction in fatigue greater than 25% compared to the control group (p < 0.05)'. I could not replicate this and it is unclear what they did with controls who had a baseline value of 0. Setting their percentage difference to 0, I got the following results for 25% reductions in fatigue scores:



Using a chi-square test, this difference was not statistically significant (X-squared = 1.614, df = 1, p-value = 0.2039).
EDIT: It looks like the authors used ITT analysis here so 8/40 responders in the control group and 17/42 in the intervention group. That's how you get the p-value of 0.04. But it is recommended to use 'Yates's correction for continuity' (the default in R) which gives a p-value of 0.07.

 

I assumed nobody would take these results seriously as indicating a real effect but Suzanne Vernon wrote on the Bateman Horne clinic website:

https://batemanhornecenter.org/promising-clinical-trials/

 

The paper says:

 

I'm sure no one will need to tinker round the statistical edges when a treatment's found that actually works. In a real remission, everything's off-the-charts better.

Just imagine it not being a problem to stand in a queue at the bar. And when the craic's still going strong and someone suggests going on to a late-night place, the calculation's only about whether you fancy it, not whether you can.

A thousand little miracles like that.

 

Yep. Though to be fair, a treatment that can improve my functional capacity by something tiny like 5% on a bell scale would be lifechanging. I might be able to tolerate sound again, have short conversation, tolerate humans in my presence, properly wash, listen to music… Like a very small improvement could completely change my life for the better.