How to Start a Clinical Trial w/ARV's for XMRV+'s

Navid

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This is the new thread to discuss how to get a clinical trial started in the US. Anyone who has ideas or knowledge on how to do this, please contribute.
 

gracenote

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This is from Rrrr's interview with Dr. Coffin.

See full interview on the thread Interviewing Dr. Coffin. See post #80.

How do you know if XMRV is the cause of CFS? If you treat the infection, and if you thus address the symptoms, then you know. Though others in his field may not agree the time is right, he would like to see a controlled clinical trial with antiretrovirals now: if they work to treat the symptoms, then we are on to something. . . .

When I asked how do we get a doctor on board without a paper confirming/replicating the link between XMRV and CFS, he said that this is the problem, can you get a controlled clinical trial before that association is confirmed? He said that is hard, but that he would like to see such a trial now, without more waiting. . . .

His hope would be that someone would set up a good controlled trial. Without doing a good placebo controlled trial, we can't move forward. But the issue is, could one justify starting a controlled trial now, without a clear association between XMRV and CFS. [Coffin says he thinks it a good idea to do this type of study now, though others may not agree.] You'd need a good way to measure that the meds are having a good virolological effect in this study. With HIV, they were surprised that the meds helped. But they did. They treat HIV with meds and the body will recover. With xmrv, he does not know if this will happen. Usually a retrovirus causes early damage, and that is the damage to the body, and treating the virus in the present does not help. This was not the case with HIV. With HIV, treating the virus *did* help, much to their surprise. If this is the same case with XMRV, that would be a good thing. But he has no idea which type of retrovirus XMRV is. We need to lobby for a controlled trial to be set up. It would not be a bad idea to do this, though others in his field would not agree.
Thanks shebacat for starting this new thread. And thanks Rrrr for doing the interview. You rrrrock!
 

Rrrr

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so glad this thread is started. thank you all for doing this.

just a reminder... I spoke to Dr. Coffin via phone on May 14. 2010, for half an hour. I have his permission to post this info from our talk on our CFS forum, but it is important to know that though I typed his answers as he spoke, and though I tried to type them as I heard them, I may have gotten Dr. Coffin's wording or even his complete thoughts wrong. And I later re-looked at the interview and tried to clarify some of my mistyping of his thoughts and wording as best I could. Again, I could have gotten some of this wrong. So please do not quote him on any of the things written above. He really does not want to be misunderstood or misquoted. Any mistakes in misquoting him are all mine. -- Rrrr
 

parvofighter

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Thank you Rrrrr and Shebacat

Firstly, a huge thank you to Rrrrr and Dr Coffin for conducting the interview, and to Shebacat for starting up this thread.

I have two key thoughts...then will be mostly incommunicado for a few days while getting a vasculitis consult:
  • A/ Might I suggest that you target the manufaturers of the 4 anti-HIV drugs that were shown by the U of Utah and Emory to have the greatest in vitro effect on XMRV? These might be the most promising early targets for a clinical trial. Here is the background info:

Researchers from the University of Utah and Emory University tested 45 compounds, including 28 drugs approved for human use, for activity against XMRV in a laboratory study. They found that 4 anti-HIV drugs raltegravir, tenofovir (Viread
, also in the Truvada
and Atripla
coformulations), zidovudine (AZT ; Retrovir)
, and the experimental integrase inhibitor L-000870812 also inhibited XMRV replication.


When used together, these agents exhibited synergistic effects, offering the potential for combination therapy to delay the emergence of drug resistance. However, the study authors noted, XMRV has limited genetic diversity compared with HIV, indicating less capacity to develop drug resistance mutations, and suggested that 2 drugs may be adequate ; notably, they were unable to select for raltegravir-resistant XMRV after trying for several months.

"While it is not yet clear if any illnesses are directly caused by XMRV, our data indicates that XMRV infections might be prevented or treated with specific antiviral agents," they concluded. "In the presence of any evidence of causality of human disease, our findings should provide the basis for designing clinical trials to treat them."


You might also consider targeting Glaxo Smith Klein, who are doing their own CFS/XMRV study.

  • B/ Don't necessarily rule out multi-national clinical trials. Admittedly, this is enlightened self-interest as a Canadian. But consider also the challenges folks are having to get funding for XMRV projects. A multi-national spread of a clinical trial might accomplish several things:

  • Prove that the virus exists outside the US - and prove that treatment works for those strains (if there are different prevalences of XMRV strains internationally)

  • Spread out the funding pain; build economies of scale, so for example administrative costs are shared across a variety of institutions internationally

  • Increase the catchment area for open-minded clinicians willing to participate in early clinical trials. Keep in mind that it may be a challenge to find such clinicians at this early stage.
Thanks again for your great efforts.

Parvo:Retro smile:
 
G

Gerwyn

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We need to decide what we are going to measure. My suggestion would be cytokines or another immunological marker such as nitrogen oxide.IL-6 levels seems linked to a great many of our symptoms.Alternatively It is possible to measure levels of gene transduction.We can then establish antiviral activity.We then need to ibclude measures of functionality PEM, treatmill cognitive function and so on. They must be objectively measueable and I would include some form of pet and spect scanning.

We need to consult a statistition to make sure that our study contains enough people to give robust generalisaeale results and is run for long enough to enable measureable changes to occur.

The in vitro work would guide us regarding of the kind of improvement we should expect over a given time and thus enable to construct the study accordinly interms of powering confidence intervals of data.

The criteria for constructing a randomised controlled trial are well documented. Essentially it is a reproducible recepie book

We need a controlled group because of remission---that could be a sticking point and ethics approval
 

jewel

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I think part of the clinical trials process -- possibly pre- formal clinical trials -- is establishing safety, but the safety profiles should already be known if you are using existing medications, unless they are being used in novel combinations. (Sis is a medical researcher; as for mayslf, I am out of my league here with regard to the science.)
 

omerbasket

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I think that perhaps the best company to adress here is "Merck", the manufacturer of "Raltegravir", and that is because:
1) Raltegravir currently seems as the best drug to treat XMRV.
2) Raltegravir, if I'm not mistaken, still has a patent - which might make it much more profitable for "Merck" to invest in research to that drug, as oppose to drugs that have generic competent (I don't know, however, if the other drugs here don't have patent too).
3) We know that Glaxo Smith Kline already makes a study regarding XMRV presence in ME/CFS - I guess since they might want to make clinical trials to see how much AZT helps for ME/CFS patients. Therefore, I guess they are already "in this bussiness", and we would not get much from trying to convince those who are already convinced...