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Status of Rituximab-ME/CFS Studies

Discussion in 'Rituximab: News and Research' started by Persimmon, Feb 15, 2012.

  1. Snow Leopard

    Snow Leopard Senior Member

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    It depends on who funds the research. Govt and academia have no problems with funding trials for drugs with patents that are about to expire. Drug corporations on the other hand..

    As far as side effect profiles go, it is completely uncertain until larger trials are done - no matter how wonderful the in vitro testing or even murine testing goes, there are always examples of drugs that had unexpected (and sometimes deadly) effects. Mammals are complicated... ;)
     
  2. Firestormm

    Firestormm Guest

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    Thanks Snow. I hadn't considered the funding.

    Hypothetically, if the Norway trial proves a success, but this new drug is introduced, will the trial results still count? I'm guessing that they will because Rituximab will presumably have been replaced. There must be precedent for this happening.
     
  3. Snow Leopard

    Snow Leopard Senior Member

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    In short, no. The new drug will have to be demonstrated to be safe and effective in trials compared to the old drug.
     
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  4. shannah

    shannah Senior Member

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    Hi Rach,

    I assume you're with Dr. Kogelnik. You're the only one that I've heard of who's starting Rituximab.

    I, for one, will be very eager to hear how it goes for you. I hope you'll keep us posted.

    Best Wishes for success!
     
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  5. Foggy

    Foggy

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  6. Snow Leopard

    Snow Leopard Senior Member

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  7. Persimmon

    Persimmon Senior Member

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    A UK Rituximab study?

    It appears that a small-sample Rituximab trial is either under way or imminent, as part of a larger UK study.
    The larger study is already funded, and being conducted by researchers who appear genuinely interested in the biological basis of ME/CFS.
    However, I haven't been able to track down details of the study.


    The CEO of the UK's Medical Research Council (MRC), Professor Sir John Savill, spoke at a meeting of the UK's All Party Parliamentary Group on M.E., held of 24th January 2012. According to the minutes of that meeting, he commented on the MRC's recent funding initiatives pertaining to biological research into ME, and communicated that:
    "One of the studies plans to use an existing cohort of patients to get a
    molecular handle on a finger print of fatigue. Within that study is a small group
    of patients who are being trialled with Rituximab, so this study seeks to
    compare and contrast symptoms with a known study."

    He was presumably referring to the research of Dr Wan-Fai Ng and Professor Julia Newton, both of the University of Newcastle. According to the ME Research UK website, they received two of the MRC's five biological ME grants, of which one was for investigation of:
    "Biological fingerprints of fatigue using whole blood gene expression profiling. Using primary Sjogrens syndrome (an autoimmune condition with several clinical features similar to ME/CFS) as a disease model, the researchers will undertake a comprehensive analysis of the immune system to identify biological fingerprints. Subsequently, they will explore whether these biomarkers are present in ME/CFS patients, and whether they have a role in improving diagnosis and treatment."

    Professor Newton's research focus is upon the role of autonomic dysfunction in the pathogenesis and severity of fatigue (and cognitive impairment) in cirrhosis, ME/CFS and Parkinson's Disease.

    Dr Ng's research focus is upon the pathophysiological mechanisms of Sjogren's syndrome (with particular reference to lymphoma risk and the symptom of fatigue); the role of autoantigen-driven immune responses and regulatory T cells in autoimmune diseases, particularly RA; and looking for T cell related biomarkers for RA.

    Further reading:
    http://www.meassociation.org.uk/wp-.../CHAIR-APPROVED-APPG-ME-Minutes-24-01-12-.pdf
    http://www.meresearch.org.uk/mrcaward.html
    http://www.ncl.ac.uk/biomedicine/research/groups/profile/julia.newton#tab_research
    http://www.ncl.ac.uk/biomedicine/research/groups/profile/wan-fai.ng#tab_research


    ** CORRECTION **
    - I've just been PM'ed with a message that Sir John's comments were alluding to Sjogren's patients being administered Rituximab as part of the study, not ME/CFS patients. (It seemed too good to be true!)
     
  8. sensing progress

    sensing progress Senior Member

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    thanks for the update Persimmon!
     
  9. Snow Leopard

    Snow Leopard Senior Member

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    Dr Wan-Fai Ng and colleagues had interest in doing a trial of Rituximab for Sjogrens syndrome patients and that is probably what they are talking about.
     
  10. Persimmon

    Persimmon Senior Member

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    Thanks SL,
    It appears you are spot on - I've just added a correction to my last post.
     
  11. oceanblue

    oceanblue Senior Member

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    Open Medicine Institute trial of Rituxan (Rituximab)
    I don't know if this study has been referred to already, but the Open Medicine Institute are putting together a mulit-centre trial

    Dr. Kogelnik interviewed in MECFS Alert Episode 22

    (Rituximab bit starts about 2/3 way through)
     
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  12. Firestormm

    Firestormm Guest

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    Can't see anything on their website Blue. Indeed the website seems a little sparse of any information. Will have a watch of the video now methinks...

    http://www.openmedicineinstitute.org/Research.html

    Edit: Yeah he does mention a pilot doesn't he? And they are involved with Ampligen. Maybe the website just doesn't get updated very often (at all)? Or it's the members of their 'research network' who are more involved? Be interested to hear more from them either way.
     
  13. LHCTom

    LHCTom

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    More on the Open Medicne Instute and Rituximab

    I'm a patient of Dr Kogelnik at the Open Medicine Institute. He gave me a brief summary of the hypothesis they are working on with Rituximab and did mention its one of the trials his collaborative group is pursuing. Here is how I understood it. One, some or all of the implicated herpes viruses, EBV, CMV and HHV-6 can enter and damage and cause B cells to become dis-regulated. B cells are key to creating antibodies specific to a particular antigen. When your B cells have been damaged by one of the viruses, they do not function correctly and may even produce harmful antibodies. Rituximab is used in cancer treatment to destroy B cells which have become cancerous. In CFS/ME, B cells that are damaged must be removed so the body can regenerate new fresh B cells. By combining antivirals and Rituximab, your current B cells are destroyed and the antivirals prevent the virus from reinfecting the new fresh B cells. The hypothesis is that by first killing off all your B cells with Rituximab and allowing your body to generate news ones while preventing re-infection of the new ones with anti-virals, one of the CFS mechanisms is halted.

    The subset of patients where this would make sense would be those where your B cells are involved. I'm not yet sure how that is determined or if its based on which of the 3 virus is involved. My understanding is that each of the 3 Herpes viruses infect immune cells but I do not know if one is specific to B cells and therefore defines the subset. I have high HHV-6 titers but none for EBV or CMV. He mentioned after testing that I probably wasn't a Rituximab trial candidate. The next time we speak, I was planning on asking about the specifics.

    The collaboration team he is working with looks quite impressive. You can see elsewhere on the news that they are now working directly with the CDC plus NIH which is new for a Clinical research team. Its a serious team and one of the members of the team is Jay Levy from UCSF's HIV research group who was a co-discoverer's of the HIV virus. Dr Kogelnik and Jay Levy are 2 of the collaborators on the work and paper that led to the finding that the XMRV virus was not involved in CFS. The combination of the quality of the team members plus their new connection with the CDC seems like very good news for CFS/ME research since its combines the best basic researchers with best clinical researchers collaborating as a team with the CDC involved in a real way. That is something that has been missing in the past.
     
  14. Firestormm

    Firestormm Guest

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    Thanks Tom. Look forward to hearing more.
     
  15. Wally

    Wally Senior Member

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    I am a patient of Dr. Kogelnik and I had planned on writing a response to a general question about Dr. Koglenik and his clinic, but when I saw this thread I thought I would add a response here about what I know about the Rituxan pilot study.

    I believe the study started late last fall and as of January (if not before) infusions were already in full swing. I qualify for the study, but I have not yet been able to participate. I am not sure what the medical qualifications for the study are, but I do have high EBV titers that would have qualified me for the Stanford Valcyte trial. I also believe that I do have positive blood results for HHV-6 (however I need to go back and look at my results again - foggy brain). My standout virus is EBV (with no other viruses except HHV-6 detected). I have also participated in both of the Stanford studies where they are looking for a host of known and unknown viruses. I will not get the results for the NIH study, but I will receive results from the Lipkin deep sequencing testing. I believe there are 150 CFS/ME patients who qualified for this particular study. I have also given my blood to the Open Medicine Institute for any research studies that will be conducted through their bio-bank.

    Dr. Kogelnik has been working closely with the original CFS/ME Rituxan researchers out of Norway. I believe that Dr. Kogelnik was the first doctor in the U.S. to start a pilot study for this drug using CFS/ME patients. It is my understanding that there is a lot of interest/collaboration in many scientific circles going on behind the scenes related to this drug, as well as other antivirals.

    The cost of being part of the pilot is very expensive $$$. This is due to the cost of the drug, as well as the cost associated with the delivery of the drug via infusion. I am not aware of any insurance company in the U.S. paying for the cost of Rituxan unless the patient qualifies for treatment related to rheumatoid arthritis or one of the other illnesses where Rituxan is already being used. However if you do not have insurance or your insurance will not cover Rituxan, it is possible that you can qualify for a patient assistance program through Genetech where the drug will be supplied without cost to the patient. The patient assistance program is available to qualified patients with a household income of $100,000 or less per year.

    I can't remember the exact number of infusions involved in the trial (perhaps someone else has already posted this answer or can provide additional information). I believe there are going to be about 5 to 6 infusions over an 18 month period. The spacing of the infusions starts at about 2 weeks, then approx. 4 to 6 weeks later, and then the time between infusions continues to be lengthened. Along with administering Rituxan during this trial, participants will also be taking an antiviral. I am unclear as to the timing of taking the antiviral in relation to receiving the Rituxan treatment, but I believe some people will take the antiviral before, some during and some after using the Rituxan. Valcyte is one of the antivirals that will be used for this trial, but I do not believe it will be limited to this particular antiviral.

    Rituxan has had a history of some very serious side effects including deaths, so entering into a trial for this drug needs to be weighed carefully by each individual. While side effects to the drug can be extremely serious, the drug has been tested in many patient populations for a number of years. The number of patients encountering life threatening side effects from the drug appears to be very low and may be related to other co-morbid conditions.

    While Rituxan is known to effect B cells, the exact mechanism of Rituxan is not yet known and it appears that it may possibly be effecting T cells, NK Cells etc... Since EBV is known to hang out in B Cells, I think patients with high EBV titers may be good candidates for seeing how this drug suppresses symptoms. It is my understanding that the three top herpesviruses that seem to pop up in a viral subset of CFS/ME patients is EBV, HHV-6 and CMV. While EBV likes to hang in B Cells, HHV-6 likes the T Cells and CMV likes to invade the monocytes. I don't believe the individual viruses restrict themselves to these sites, but this is where they seem to like to party. Could Rituxan be acting as an antiviral? I don't know, but it is interesting that Ampligen is also thought to have antiviral properties.

    Back in the late 1980's and early 1990's the idea of a herpesvirus (EBV) having a causal effect in CFS/ME was shot down in large part to the work of Dr. Strauss and his research using Acyclovir (fairly low dose given for 6 weeks). Looking at the reseach conducted by Dr. Lerner, Dr. Glasser, Dr. Montoya, Dr. Kogelnik, Dr. Peterson and other pioneering CFS/ME specialists the herpesvirus link to this illness, as well as to other neuroimmune illnesses such as ME, RA, Parkinson's and Autism may be much closer than we realize. Is it possible that 20 plus years of research into this illness could have been so derailed by one psychiatrist??? Dr. Strauss was a psychiatrist at the NIH tasked to investigate the illness that occurred in Incline Village and Lyndonville. Dr. Strauss passed away in 2007, so it will be interesting to see if his findings related to herpesviruses and "CFS" maybe coming to an end.
     
  16. Firestormm

    Firestormm Guest

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    Posted on IiME: http://www.investinme.org/InfoCentre-Library-NMEA-Newsletter-1203.htm

    What is Happening with the Research into ME and Rituximab?

    By Anette Gilje

    Secretary General, Norwegian ME Association

    The cancer doctors ystein Fluge and Olav Mella, Haukeland University Hospital, published their study on ME and rituximab last autumn. Following their sensational and promising findings that some people with ME had benefitted from the immune modulator rituximab, the Government allocated two million Norwegian Kroners (approx. 220 000 ) to the Western Norway Regional Health Authority to help funding a larger follow-up study.

    This is far from enough to fund a larger, double-blinded multi-center study which is necessary to determine the scientific research question: Does rituximab have an effect on this patient group, or not, says Professor Mella.

    We do believe it has, but this has to be confirmed in a larger study to gain scientific credibility internationally. To be reasonably certain to answer the question, the study probably has to include between 120 and 140 carefully selected patients that meet the Canadian Consensus criteria. The patient-sample will be divided into two groups, one of which will receive active treatment with rituximab, the other placebo (i.e. inactive substance). Both groups will be closely observed for potential effects and adverse reactions.

    Providing the study can confirm a significant effect in the group that was given rituximab and the adverse reactions are acceptable, the placebo group will be offered treatment with rituximab at a later point of time.

    A scientific study of this scale cannot be initiated before the whole project is fully funded. So far Drs Fluge and Mella are working to a draft protocol for a larger study in corporation with the ME/CFS-Centre, Oslo University Hospital (Aker). When the preliminary protocol is completed, it is time to establish collaborations with other research communities that want to take part in the study. After that the research protocol will be submitted to the Committee for Medical and Health Research Ethics and the Norwegian Medicines Agency.

    Professor Mella says it is extremely important that the research centers included in the study are dedicated to the task. They need people who are very good at diagnostics and that can administer the rituximab treatment in a safe manner for the patients. - If you cant accommodate this, its probably better for the study to be carried out in fewer institutions.

    Adverse reactions

    Rituximab is known to have some serious, but very rare adverse reactions.

    Our experiences in working with cancer patients show that this is a drug that do not trigger a lot of adverse reactions, Mella says.

    What you do, is to deplete the B-cell lymphocytes which are normally responsible for production of antibodies. Because this is done only for a limited period of time, many of the mature B-cells are still circulating in the blood stream. The increase in infections in most patients receiving this treatment is small. There is, however, a theoretical risk for serious infections. That is why it is necessary to be alert when looking for emerging signs of infection.

    Dr Mella explains that rituximab is a protein substance that is partly produced from human material and partly from mouse material. The tendency for allergic reactions is increased compared with some other drugs. That is why it is important that the patients receive the drug under observation, preferably at a rheumatological-, neurological- or a cancer ward.

    If you are used to administer rituximab and know what to do if allergic reactions occur, we see this as an easy treatment, Dr Mella reassures.

    The patients must be under observation for some hours when they receive the treatment in the ward, and they are admitted for 24 hours to make it possible to deal with potential adverse reactions.

    It is important to stress that we do not know if ME patients may have more or other side effects compared to patients with cancer or rheumatological diseases.

    Biomarkers

    Drs Fluge and Mella have worked for almost three years in their search for biomarkers for ME, thanks to the funding from Western Norway Regional Health Authority. In their search, biological samples from the study participants are investigated in the laboratory. The patients clinical picture is the researchers starting point in their search for biomarkers. From there they can reflect where the problem might be located and search for abnormalities. Dr Mella admits that there is always a need for money for research, more can be done and things can move forward a little quicker.

    Translated by

    Ellen V. Piro and Eva Stormorken

    Norwegian ME Association

    16th March 2012

    The translation has been approved by Professor Olav Mella and is published with his permission.
     
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  17. Enid

    Enid Senior Member

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    Thanks for posting Firestormm - hope their studies can continue without more delay.
     
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  18. Wally

    Wally Senior Member

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    It is my understanding that the size of such a study would probably cost between three to five million dollars. If this research can be conducted with an international consortium of researchers and clinicians it has the potential to blast open some new frontiers in treatment of this illness. I thought Dr. Bell's remarks about Rituxan being the most promising potential treatment that he has seen in 25 years was quite significant. Especially spoken by someone who has fought so gallantly in the trenches to triage symptoms while continuing a passionate quest in search of answers to this debiltating illness.
     
  19. Tia

    Tia Senior Member

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    Just wanted to say thank you to Tom and Wally for their explanations and reviews on Dr. Kogelniks work, very interesting read. :thumbsup:

    Firestormm: I'd be surprised if they weren't granted more funds for ther studies since it's Norway. That country is rich due to their oil and it usually isnt a problem of getting funds. Same thing in sweden. Scandinavia is great that way, so if they dont have the money for it, they will. The state usually pays for this.
     
  20. Firestormm

    Firestormm Guest

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    Hi Tia,

    Like Wally, I think perhaps the only way to proceed is for a European or International joint venture. Here in the UK the ME Association are looking to help fund a similar clinical trial. The cost will be approx. 200,000 to get it off the ground (I don't have specific details).

    Charities do fund research of course but clinical trials? Might be a first particularly in the UK. Still, if all the charities banded together, along with the regulatory authorities perhaps, and reached across the North Sea? Anyway, the question will be raised at the next Forward ME meeting (which is a groups comprising charities and Members of Parliament).

    I do still have personal reservations about Rituximab and I'm not convinced a clinical trial necessarily means 'full steam ahead' or that such a trial among a much larger cohort will be successful. But, what the heck, right? Let's give it a spin. We've got nothing to lose.

    Perhaps even the drug manufacturer can be persuaded to help fund a proper trial (especially if the parties above all dip in to their pockets)!
     

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