B-Lymphocyte Depletion in Patients With ME/cfs: A Randomized, Double-Blind, Placebo-Controlled Trial (2019) Fluge et al

[Andy]

I thought I could remember that we had more of a discussion on why there might have been so many responders in the placebo group, if I'm right can anybody point me towards it?

Secondary outcomes included [..] changes from baseline to 18 months in these measures and physical activity level

It would also be nice to know what this actually showed and how it was measured, does anybody have access to the paper for this detail? I still can't access it via Sci hub.

 

[ME/CFS Skeptic]

I found it interesting that in the 2015 report in PLoS ONE, they mention that the responder group had an impressive number of steps per day: almost a mean of 10.000.

12 out of 14 major responders in this study measured physical activity for 4–6 consecutive days in the time interval 15–20 months follow-up, with a mean value for “mean number of steps per 24h” 9829 (range 5794–18177)

One would think that this was more than just a placebo effect.

 

[Trish]

Does it say what their step count was before treatment?

 

[ME/CFS Skeptic]

Does it say what their step count was before treatment?

Good point, don't think so, no. Should reread the papers to be sure. But I suspect that one can assume that patients receiving a ME/CFS diagnosis in this study would have had a much lower amount of steps per day.

 

[lycaena]

I thought I could remember that we had more of a discussion on why there might have been so many responders in the placebo group, if I'm right can anybody point me towards it?

https://www.s4me.info/threads/rituximab-and-placebo-response.9704/ (discussion of this thread mostly about the open trial)

 

[adambeyoncelowe]

Good point, don't think so, no. Should reread the papers to be sure. But I suspect that one can assume that patients receiving a ME/CFS diagnosis in this study would have had a much lower amount of steps per day.

I think studies that measure step counts usually show that there's a wide range of activity with ME patients. Some are under- or over-active (as in over 10K steps per day), some are in the middle, but these figures are largely consistent (i.e., there isn't evidence of boom and bust).

I think it's feasible that some mild patients are actually doing more than 10,000 steps per day, provided they do them at their own pace. Especially those milder patients who manage to stay in employment.

ETA: I think Ramsay and the ICC both mention that athletes who get ME might still appear to do a lot comparatively, but it's still a relatively large loss of function compared to what they could do before.

 

[Trish]

There is also the question of how accurate step counters are. Commercial wrist worn ones are measuring wrist movement. Taking a jumper off while sitting has counted as 20 steps on mine!

 

[adambeyoncelowe]

There is also the question of how accurate step counters are. Commercial wrist worn ones are measuring wrist movement. Taking a jumper off while sitting has counted as 20 steps on mine!

Fanning oneself can cause hundreds of 'steps' to materialise out of nowhere too. The counters may not accurately measure steps but they might be considered a loose measure of 'activity' (or at least movement) instead.

Comparing patients with each other is probably less useful than comparing patients with themselves. That and using the same step counter over the course of the intervention might be useful at capturing changes in movement frequency.

My steps doubled when I changed to a different step counter. I wasn't more active, but it was measuring things differently. However, my activity levels are still the same.

 

[Andy]

https://www.s4me.info/threads/rituximab-and-placebo-response.9704/ (discussion of this thread mostly about the open trial)

Awesome, thank you.

 

[Rain]

There is also the question of how accurate step counters are. Commercial wrist worn ones are measuring wrist movement.

They used the brand Sensewear - used on the upper arm.

Edit: Sensewear, also track a lot more than a Fitbit. Position (standing/sitting/horizontal), temperature, galvanic skin response and more.

 

[Andy]

I've now got access to the text of the paper (thanks to the person helping me out there).

It says

Further, the same outcome measures did not change significantly from baseline to 18 months of follow-up, nor did mean number of steps per 24 hours between baseline and repeated assessment in the time interval 17 to 21 months (Table 2). In general, during 24 months of follow-up, both treatment groups had slight but significant improvements over time in mean values for all self-reported outcome variables and for physical activity level

I was initially confused by number of steps not increasing but physical activity level increasing but they explain

Additional secondary end points defined in the study protocol were differences between the treatment groups in repeated measurements of SF-36-mean5 (mean of raw scores for physical function, bodily pain, vitality, social function, and general health) through 24 months of follow-up and changes from baseline to 18 months in maximum number of steps per 24 hours and mean and maximum duration of physical activity of at least 3.5 metabolic equivalents (METs) per 24 hours.

So, on average, both groups did have a "slight" improvement in physical activity level but neither groups increased the number of steps taken, despite 35% of the placebo group and 26% of the treatment group self-reporting an improvement.

So, to me, this strongly suggests, at best, an improvement more in how the patients managed their ME through pacing than for any other reason, as I would argue that any practical improvement in their ME would result in noticeable increases in step count. I know that when I pace properly I can be far 'busier' around our home but that doesn't translate into any substantial increase in steps. I suppose it depends what, practically, 3.5 metabolic equivalents (METs) equates to in real life.

To answer that, there is this, from https://en.wikipedia.org/wiki/Metabolic_equivalent


Does how I'm thinking of this match what other people experience?

The reason I'm looking at it is that I have been asked if, from a patient point of view, the self-reported improvement in fatigue is likely to be meaningful in any way. I'm of the opinion that, without an increase in step count, it isn't.

 

[Trish]

The reason I'm looking at it is that I have been asked if, from a patient point of view, the self-reported improvement in fatigue is likely to be meaningful in any way. I'm of the opinion that, without an increase in step count, it isn't.

No questionnaire measure I've seen of fatigue is meaningful in ME, I think. We need objective outcomes.

I probably would have self reported more fatigue when my ME was mild and I was doing more, so the need to stop because of fatigue was more troublesome and the pain and drained feeling were worse. Now my life has more or less ground to a halt, I don't have to stop because of fatigue as often, because I'm not doing anything anyway. Similarly my pain probably less now too, because the more I do physically, the more pain I get.

When I had young babies and hardly any sleep I was very very fatigued, but also perfectly healthy.

Fatigue is such a slippery concept, measuring it is with a questionnaire is like measuring integrity with a ruler. It's meaningless.

 

[Ebb Tide]

Jennie Spotilla writes about METs in relation to her 2 day CPET in her Occupy Me blog: http://occupyme.net/exercise-testing-and-results/

Full Compendium Physical Activities of METs here: https://sites.google.com/site/compendiumofphysicalactivities/

METs in relation to pwME and 2 CPET is also discussed on pages 11 & 12 of the Workwell paper published earlier this year, discussed here, with useful information on Table 7:

https://www.s4me.info/threads/front...ion-in-me-cfs-prov-2019-davenport-et-al.8482/

If I am reading it correctly, Workwell found that 3.5 METs is beyond what the patients they have tested can manage and stay under their VAT with or without PEM.

 

[Sam Carter]

Am I right in thinking that the results of the three substudies mentioned in the trial's protocol have not been published? [*]

Even if there were no differences between the placebo and rituximab groups, I'd like to see how the participants' endothelial, cardiopulmonary and gastrointestinal function compared to what would be expected in age and sex matched healthy people.

[* from: https://clinicaltrials.gov/ct2/show/NCT02229942]

""""""
Three substudies will be performed:

Endothelial function: assessment of Flow-Mediated Dilation and skin microcirculation at baseline and repeated during the time interval 17-21 months.

Cardiopulmonary exercise test for two following days: assessment at baseline and repeated during the time interval 17-21 months.

Gastrointestinal function: assessment at baseline and repeated during the time interval 17-21 months.
""""""

 

[rvallee]

There is also the question of how accurate step counters are. Commercial wrist worn ones are measuring wrist movement. Taking a jumper off while sitting has counted as 20 steps on mine!

I have seen far too many times my Fitbit celebrating reaching the daily step count after spending a full hour or more sitting down to trust it.

The accuracy on wrists is terrible. And it wouldn't be much better on ankles, especially those with restless leg.

 

[Snowdrop]

This conversation has made me notice that I actually have more steps when feeling worse than usual. I expect this is a result of when I'm feeling more ill I actually move more -- not walking but agitated movement because I'm uncomfortable.

I often wondered (for like a nanosecond) why this seemed to be. But this thread made me stop and consider this is what is likely going on. I know I'm not walking more because my steps are so restricted and routine.

 

[andypants]

This conversation has made me notice that I actually have more steps when feeling worse than usual. I expect this is a result of when I'm feeling more ill I actually move more -- not walking but agitated movement because I'm uncomfortable.

I often wondered (for like a nanosecond) why this seemed to be. But this thread made me stop and consider this is what is likely going on. I know I'm not walking more because my steps are so restricted and routine.

When I’m feeling worse I tend to move more too. Partially because I crave distraction from feeling horrible and partially from being wired.

 

[Marky]

When I’m feeling worse I tend to move more too. Partially because I crave distraction from feeling horrible and partially from being wired.

Yes.. Haha

Ive had a worsening this summer after gradual exercise, and I have ended up doing whatever makes me feel bad twice because my thinking is like "there is NO way im going to bed unable to finish the dishes", so I go back to do it only to get PEM again.

 

[Andy]

Am I right in thinking that the results of the three substudies mentioned in the trial's protocol have not been published? [*]

As far as I'm aware, yes, you are right.

 

[Rain]

@Jonathan Edwards

Do you have a thoughts on VanElzakkers Twitter-comments on immunosuppression and ME? The theories behind both Rituximab and Cyclophosphamide was “switch off, switch on”, not permanent suppression, was it not?

Edit: I am not the one discussing with him on Twitter.