Trial design for drug trials for ME/CFS - discussion thread

Caroline Struthers

Caroline Struthers

Senior Member (Voting Rights)
Posts discussing trial methodology and possible drugs to trial have been moved from a thread about a specific trial
The LIFT trial (OMF) - Pyridostigmine (mestinon) and Low Dose Naltrexone (LDN)


Is there any reason why there couldn't be an application to the NIHR or other funder to copy the LIFT trial blueprint in the UK/Europe? Perhaps have a protocol for the trial designed by patients. I want to try and develop a standard way of involving patients in designing trials called Trialblazers - recent presentation of this idea here . Perhaps even testing different "promising" off label medications from a patient/doctor generated shortlist - ie not LDN and Mestinon, but other/s
 
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Caroline Struthers said:
Is there any reason why there couldn't be an application to the NIHR or other funder to copy the LIFT trial blueprint in the UK/Europe? Perhaps have a protocol for the trial designed by patients. I want to try and develop a standard way of involving patients in designing trials called Trialblazers - recent presentation of this idea here . Perhaps even testing different "promising" off label medications from a patient/doctor generated shortlist - ie not LDN and Mestinon, but other/s
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Do you think it would help with a funding application to explicitly acknowledge that it is copying from LIFT, but maybe add in the commitment to turbo-charge it with the involvement of patients - ie make it deliver useable results much much faster by being more pragmatic about the design - maybe randomise in clusters, deliver the treatments via primary care... this is a bit of stream of consciousness.....And also avoid using an annoying acronym unless patients approve it in advance :-). "LIFT-OFF" anyone?
 
Caroline Struthers said:
Perhaps even testing different "promising" off label medications from a patient/doctor generated shortlist - ie not LDN and Mestinon, but other/s
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I don't know whether it might be appealing to funders, but I can see there could be issues about trialling medications that might result in it getting bogged down. We don't really have enough medication options to try, at least not meds that have enough of a potential disease modifying action to show clear outcomes.

I think we'd need questions we're likely to be able to answer. One of mine, for instance, would be does pre-emptive rest actually help people with moderate ME/CFS avoid PEM? I doubt it would have any appeal whatsoever to a funder, but there might be other questions that are more substantial/imaginitive/etc.
 
Kitty said:
I don't know whether it might be appealing to funders, but I can see there could be issues about trialling medications that might result in it getting bogged down. We don't really have enough medication options to try, at least not meds that have enough of a potential disease modifying action to show clear outcomes.

I think we'd need questions we're likely to be able to answer. One of mine, for instance, would be does pre-emptive rest actually help people with moderate ME/CFS avoid PEM? I doubt it would have any appeal whatsoever to a funder, but there might be other questions that are more substantial/imaginative/etc.
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The only reason I went for trialling medications was firstly that it hasn't been done properly in the past. LIFT seems to be a good template for a trial of medications for ME. Also, testing medications was second in the top ten list generated by the James Lind Priority Setting Partnership for ME research https://www.jla.nihr.ac.uk/priority-setting-partnerships/ME-CFS/top-10-priorities.htm. James Lind is supported by the NIHR, so I would hope they would welcome an application to design a trial to test potentially helpful medications, especially with a placebo control, as they are doing with LIFT.
 
Caroline Struthers said:
The only reason I went for trialling medications was firstly that it hasn't been done properly in the past.
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It's not that I don't think it's a good idea, and it would be popular with patients. I just worry about what the realistic medication options are, and how many have enough convincing potential to sway a funder. Specially if it's not going to include LDN or Mestinon.
 
Kitty said:
It could be, but there seem to have been endless problems getting the manufacturer to part with any—or something like that. That could be resolved now, though, I've lost track. It seems to have been on the list of possible disease modifiers for yonks.
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yes, someone told me there was an ampligen trial planned, or even underway, but there were issues with supply of it. I wrote to the lead researcher involved and didn't hear back from him...will go back and look for his name and post to see if anyone else knows anything
 
Caroline Struthers said:
yes, someone told me there was an ampligen trial planned
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I remembered wrongly...it was a trial of LDN for Long Covid I was alerted to, NOT Ampligen for ME. The researcher was Louis Nacul, who was allegedly having problems getting hold of it, but he didn't respond to an inquiry about the trial. This is the link to the trial registration so it seems to be going ahead fine https://clinicaltrials.gov/study/NC...ntr=Low Dose Naltrexone&rank=1#study-overview
 
MEMarge said:
I tyhink David Strain isn interested in Ampligen
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I filled in a form to contact him when I found out he's got one of these new roles of UK Parliament Thematic Research Lead for Health

https://www.parliament.uk/trls/
Health - Dr David Strain, University of Exeter

Based on the concept of Chief Scientific Advisers, Thematic Research Leads (TRL) bring their impartial expertise, extensive policy knowledge and strong network of research connections to a variety of teams in and out of Parliament. They work for three days each week in Parliament, while continuing their role in their own academic institution. Each TRL leads on a specific policy area. Following a successful pilot, six new thematic areas have been created and the new TRLs, including David Strain will join Parliament in September 2024:

I filled in this form to re-introduce myself and the Trialblazers project which I'd talked to him about a few months ago with Sonja Choudhery. At the time Sonja and David seemed to think it wasn't focussed enough on ME, as it was aiming to develop a way of involving patients and the public in trial design in general, using ME as a proof of concept/case study.
https://forms.office.com/Pages/Resp...s2as3NStUMDFVTzFDNkJDTVBRUVE5WjVSMlFOQVY3NS4u

I thought I'd saved the text of the form, but it seems it's lost in the ether. It won't reach him until September either, so I'll probably write directly to him as well. Will mention Ampligen
 
Some drugs being trialled elsewhere for ME and LC that UK trials would be worth considering if the current trials bear fruit

Rapamycin
IVIG/SCIG
Baricitinib
Bc007
Truvada
Daratumumab


There is also a b cell depleting drug in trial for fibro in the UK, and tocilizumab for LC which should be tried in ME if there is a positive result. Also bateman hornes antiviral plus celecoxib and two drugs in canada i dont remember the names of.

I agree that mestinon/ldn would be a good starting point but just thought I'd flag these up in case you weren't aware of any of them.

It would be great to do a proper blinded ampligen trial with a well selected cohort and put the question to bed once and for all.

Edit: Baricitinib LC trial won't read out til 2029 so a trial before then would be strongly preferable imo, considering the JAK STAT based theories for ME and LC.
 
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Caroline Struthers said:
Will mention Ampligen
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From an immunologist point of view, ampligen fills me with no enthusiasm. It is unclear to me what if anything it does to the immune system. It seems to be a drug someone made hoping it would be useful but for very obscure reasons. We already have trials that came to no very clear conclusion.

The real problem with setting up trials in ME/CFS at this point is that we do not have any of the sort of preliminary data one normally wants to justify exposing people to unknown dangers. With the initial rituximab study at least there was a clear hypothesis relating to B cells. For ampligen we don't even know what it does, if anything.

A lot of the drugs being suggested are really quite dangerous and in unpredictable ways. Both rituximab and tocilizumab were tried in polymyalgia with disastrous effects of an unpredictable sort. And at least there was a strong theoretical basis for trying them.
 
Jonathan Edwards said:
From an immunologist point of view, ampligen fills me with no enthusiasm. It is unclear to me what if anything it does to the immune system. It seems to be a drug someone made hoping it would be useful but for very obscure reasons. We already have trials that came to no very clear conclusion.

The real problem with setting up trials in ME/CFS at this point is that we do not have any of the sort of preliminary data one normally wants to justify exposing people to unknown dangers. With the initial rituximab study at least there was a clear hypothesis relating to B cells. For ampligen we don't even know what it does, if anything.

A lot of the drugs being suggested are really quite dangerous and in unpredictable ways. Both rituximab and tocilizumab were tried in polymyalgia with disastrous effects of an unpredictable sort. And at least there was a strong theoretical basis for trying them.
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I am currently weighing up whether going into the surgery to get an issue checked out is worth the crash and covid risk, or whether I should wait weeks for a home visit. Doing nothing is not neutral because having severe ME means normal everyday things make you sicker. It is difficult to access medical care. Every day I am in this state is dangerous. Getting a serious illness while this sick could cause a huge deterioration. We are vulnerable to an NHS that doesn't believe us and hates us. Finding a drug is urgent.

I was talking about if there is a positive signal in another trial for LC or ME. Which last time this discussion occured you said would merit a UK trial.

I wasn't aware of that r.e. tocilizumab. Nobody here was suggesting rituximab.

Aware of the dangers of Baricitinib but there is also a pretty clear hypothesis about why it might work.
 
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Jonathan Edwards said:
From an immunologist point of view, ampligen fills me with no enthusiasm. It is unclear to me what if anything it does to the immune system. It seems to be a drug someone made hoping it would be useful but for very obscure reasons. We already have trials that came to no very clear conclusion.

The real problem with setting up trials in ME/CFS at this point is that we do not have any of the sort of preliminary data one normally wants to justify exposing people to unknown dangers. With the initial rituximab study at least there was a clear hypothesis relating to B cells. For ampligen we don't even know what it does, if anything.

A lot of the drugs being suggested are really quite dangerous and in unpredictable ways. Both rituximab and tocilizumab were tried in polymyalgia with disastrous effects of an unpredictable sort. And at least there was a strong theoretical basis for trying them.
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That is a very important point.

Personally I am keen to avoid drugs of known high toxicity, so wouldn’t sign myself up for any trial of chemo or immune suppression and would think carefully about anti virals.

But I wonder about drugs that have been knocking around a long while, generally considered relatively safe. Is that still an ethical problem be cause of the ‘relative’ part or because we don’t know what ME is, so we don’t know what’s okay for us?

I just want some relief. I don’t think it’s fair that only people who can afford private healthcare can experiment or have hope of trying things that could improve their lives.

But I can also see that anything might prove hard to justify.
 
V.R.T. said:
Finding a drug is urgent.
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I understand that but we cannot expect individuals to take part in trials on the basis of the good of all unless they are honestly told that the chances of something very bad happening to them are almost certainly greater than anything very good. Given that we can be fairly sure that is true for 99 out of every 100 drugs in the pharmacy it is difficult to set up trials with good levels of recruitment on that basis.

I realise that rituximab is no longer being suggested, I simply mentioned its use in poly myalgia as an example of how unpredictable these things are.
 
Ash said:
But I wonder about drugs that have been knocking around a long while, generally considered relatively safe. Is that still an ethical problem be cause of the ‘relative’ part or because we don’t know what ME is, so we don’t know what’s okay for us?
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Not that many drugs are that safe to be honest. I am horrified now to think of how I used to think they were. Everything is relative, of course, but I have tried to think of 'safe' drugs that might be worth trying and consistently failed to find anything I can get enthusiastic about. Naltrexone seemed a reasonable thing to try simply because they are a lot of reports of individual benefit. You might say that about ampligen but there have been trials already there with inconclusive findings.
 
Jonathan Edwards said:
I understand that but we cannot expect individuals to take part in trials on the basis of the good of all unless they are honestly told that the chances of something very bad happening to them are almost certainly greater than anything very good. Given that we can be fairly sure that is true for 99 out of every 100 drugs in the pharmacy it is difficult to set up trials with good levels of recruitment on that basis.

I realise that rituximab is no longer being suggested, I simply mentioned its use in poly myalgia as an example of how unpredictable these things are.
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I understand your perspective, however I was talking about UK trials of drugs that are in trial elsewhere in the world on the basis of a hypothetical positive signal from said trials.

Baricitinib being the exception and maybe that was a bit rash.
 
V.R.T. said:
Some drugs being trialled elsewhere for ME and LC that UK trials would be worth considering if the current trials bear fruit

Rapamycin
IVIG/SCIG
Baricitinib
Bc007
Truvada
Daratumumab


There is also a b cell depleting drug in trial for fibro in the UK, and tocilizumab for LC which should be tried in ME if there is a positive result. Also bateman hornes antiviral plus celecoxib and two drugs in canada i dont remember the names of.

I agree that mestinon/ldn would be a good starting point but just thought I'd flag these up in case you weren't aware of any of them.

It would be great to do a proper blinded ampligen trial with a well selected cohort and put the question to bed once and for all.

Edit: Baricitinib LC trial won't read out til 2029 so a trial before then would be strongly preferable imo, considering the JAK STAT based theories for ME and LC.
Click to expand...
So useful -thank you!
 
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