Norwegian Rituximab study starting 2014

[LaPerla]

http://mariasmetode.no/2014/03/rituximabstudies-an-update/

Scroll down for english translation.

 

[Bob]

Some interesting details about the study:

The researchers aim to include 152 patients from Norway.

In the study, half of the patients have rituximab and the other half salty water.

Everyone will get a total of six infusions...

Two infusions two weeks apart initially, then infusions after 3 , 6, 9 and 12 months .

The study will be double blinded until the last patient has been included in the 24 -month follow-up.

So it will be a double-blind trial with 152 patients (half receiving a placebo of salty water) with a 24 month follow-up period.

 

[CBS]

Thank you for the update. Forgive me if this seems obvious but I am assuming that study design takes into account that the placebo - saline, depending upon how much - can be a short-lived treatment for OI symptoms in ME/CFS patients. I suspect that even if the placebo controls are given enough saline to have a short term effect, the improvement for those responding to Rituximab will still be clearly superior, perhaps the difference being slightly smaller than it otherwise would have been. All that said, I'm not sure that I have a better idea for an appropriate control.

 

[Esther12]

24 month follow-up sounds like a good idea for a solid result... means a long wait for us though!

 

[Legendrew]

Thank you for the update. Forgive me if this seems obvious but I am assuming that study design takes into account that the placebo - saline, depending upon how much - can be a short-lived treatment for OI symptoms in ME/CFS patients. I suspect that even if the placebo controls are given enough saline to have a short term effect, the improvement for those responding to Rituximab will still be clearly superior, perhaps the difference being slightly smaller than it otherwise would have been. All that said, I'm not sure that I have a better idea for an appropriate control.

I remember having this discussion in another thread a while ago and we concluded that while saline may have transient helpful effects they would not be very pronounced and most importantly would not be long lasting. For those in the medical profession to take such a study seriously it needs to be double-blinded with a control and it'd likely raise more concern if they used a different placebo than the research standard.

 

[CBS]

I remember having this discussion in another thread a while ago and we concluded that while saline may have transient helpful effects they would not be very pronounced and most importantly would not be long lasting. For those in the medical profession to take such a study seriously it needs to be double-blinded with a control and it'd likely raise more concern if they used a different placebo than the research standard.

Perhaps one way to deal with this would be to have three groups. The treatment and placebo groups as described and then a control in which nothing was given and the natural course of the illness was documented in an appropriately matched group of patients. Again, this would likely only be of use if the saline was given in a quantity and/or frequency that was likely to have an actual therapeutic effect (my guess would be anything more than 500 ml or more often than once a week).
Another issue that would come into play with the potential therapeutic effect of saline is when follow-up questions were asked. It would definitely be a good idea to avoid having either group complete any reports/measures within a day or two of having received an infusion (treatment or control).

 

[Firestormm]

So approval has not yet been obtained, which means no definitive start date until they do I guess.

 

[Bob]

@CBS, I was slightly concerned about the saline placebo until I thought about the time scale involved. It's a 24 month study, and any effects from the saline would likely be short lived. I don't know at what points they are assessing the participants but it will probably be something like 3 months, 6 months, 12 months and 24 months. It won't be on the days following the infusion.

 

[Jonathan Edwards]

I think the point to remember here is that the saline is being given as placebo simply because the rituximab comes in that amount of saline. This is not a standard placebo - it just an 'empty rituximab bag'. All trials like this can only detect differences - in this case the difference in improvement between the two. So everything except the rituximab has to be the same if possible. It does not matter if there are any improvements due to the saline - they get cancelled out of the result. Another point is that a litre of saline once off is no big deal, except psychologically. This litre is given over a period of about five hours usually. So the impact on the circulation will actually be less noticeable than drinking a large bowl of salty soup for lunch - or eating a packet of crisps washed down with coke. We all take in this sort of amount of water quicker than that in a day and eat more salt than that in a big salty meal. All the salt and water gets into the circulation from the gut - and probably quicker than by very slow drip. The psychological impact can be significant though - which is the key reason for making the placebo as similar to the rituximab bag as possible.

 

[Firestormm]

I think the point to remember here is that the saline is being given as placebo simply because the rituximab comes in that amount of saline. This is not a standard placebo - it just an 'empty rituximab bag'. All trials like this can only detect differences - in this case the difference in improvement between the two. So everything except the rituximab has to be the same if possible. It does not matter if there are any improvements due to the saline - they get cancelled out of the result. Another point is that a litre of saline once off is no big deal, except psychologically. This litre is given over a period of about five hours usually. So the impact on the circulation will actually be less noticeable than drinking a large bowl of salty soup for lunch - or eating a packet of crisps washed down with coke. We all take in this sort of amount of water quicker than that in a day and eat more salt than that in a big salty meal. All the salt and water gets into the circulation from the gut - and probably quicker than by very slow drip. The psychological impact can be significant though - which is the key reason for making the placebo as similar to the rituximab bag as possible.

Not addressed specifically to Prof. Edwards, but can anyone remember for me, how they will attempt to measure improvements? Only I have forgotten. Thanks