Rituximab Phase III - Negative result

[Londinium]

And how would you explain that Ron Davis and his team found the same anomalies in metabolism in every ME patient and that his nano-chip also works in every ME patient?

FWIW, I believe the nano-chip test was only on severe patients. But to be honest we have little to go on as it’s not been published in a peer reviewed paper and I will remain wary of the nano-chip findings until it is, so that sufficient detail on possible limitations/confounding factors can be seen.

(Same with the flow mediated dilation stuff above - looks interesting but needs more info, for example on whether sedentary vs healthy controls would give a similar difference).

 

[Martin aka paused||M.E.]

FWIW, I believe the nano-chip test was only on severe patients. But to be honest we have little to go on as it’s not been published in a peer reviewed paper and I will remain wary of the nano-chip findings until it is, so that sufficient detail on possible limitations/confounding factors can be seen.

(Same with the flow mediated dilation stuff above - looks interesting but needs more info, for example on whether sedentary vs healthy controls would give a similar difference).

I thought they successfully tried it on the second round (non severe) patients too...

 

[pibee]

I wonder if there's anyone out there who hasn't tested "positive" on these antibodies.

weird, i got the impression almost eveyone tests vey low..i couldnt find anyone who had even close to mine results..highest is Muscainic M4 result 49 > 7.0 U/ml: positive.

But i still dont know what it means...


Since cut off is top 10% results in Loebel et al, healhy person has 1/10 chance scoring positive (but if you look at graphs CellTrend seems to put cut off at 5%, but not sure, just basing on graphs from Loebel study), so for 9 antibodies would be 61% (1-0.9^9) chance of scoring positive for at least one antibody

If you disregard the fact that correlations in scores for antibodies are quite high 0,5-0,8, so this lowers number of healthy controls that score positive, but still considerable number will have at least 1 positive

And most PWCFS's I've seen are pos for 2/9, which we dont know how significant is, if t is at all
Without more raw data from Loebel study

 

[pamojja]

what was my first thought yesteday when negative results were published...was sadness how many more suicides in the following years will come because of not only lack of treatment but recognition it's a real disease..so isolation...because positive results would forever shut psychobabblers mouth

The point I was making yesterday is, there also isn't any hope even with well studied deathly multi-factorial diseases like CVD or cancer. It still can be beat. With preliminary science of natural compounds, which will never get approved for treatment. Since none would waste incredible amounts on double-blind studies for natural compounds which can't be patented, and profited from. Sure CVD and cancer patients are more acknowledged, from personal experience the treatment options offered are just as crazy and hopeless most of the time.

 

[Martin aka paused||M.E.]

The point I was making yesterday is, there also isn't any hope even with well studied deathly multi-factorial diseases like CVD or cancer. It still can be beat. With preliminary science of natural compounds, which will never get approved for treatment. Since none would waste incredible amounts on double-blind studies for natural compounds which can't be patented, and profited from. Sure CVD and cancer patients are more acknowledged, from personal experience the treatment options offered are just as crazy and hopeless most of the time.

I don't know if I get the point. But I would be very happy if I had those "crazy" treatment options like cancer patients...
And there are "natural" treatment options in lets say cancer with modern studies behind that doctors use... for example high dose vitamin c infusions...

 

[pibee]

Study dont get funded if product cant be patented.
If one double blind placebo showed IVIG at 2g/kg worked for 40% of CFS, why there wasnt a study later?
Only 3 studies, all together, all small.
Same with other natural treatments. Which doent mean they work.

 

[jimells]

A slide showed they found p-001 decreases in flow mediated dilation in both RITUXME-baseline patients and pilot patients, and also a prolonged systemic hyperemia response after a POHR-test (http://www.perimed-instruments.com/post-occlusive-reactive-hyperemia)

They ask why?

I suggest they might want to look at the role of mast cells in ME. Mast cells behaving badly can cause an incredible array of symptoms. A Pubmed search on "hyperemia and mast cells" turns up over 80 articles.

There is a substantial body of research on mast cells. They can cause most or all of the symptoms commonly reported by ME patients. But so far as I can find out, no researcher has even bothered to ask the question, "Could mast cells be causing ME symptoms?" or even, "How many ME patients also have mast cell problems?"

It sounds too easy to be true, and it has only been a few weeks, but since I added 1/2 aspirin tablet every 4 hours to my regimen of anti-histamines, I have finally managed to stabilize my blood pressure to the point where I can actually stay upright a few hours a day without triggering PEM, migraines, and IBS.

The research literature on this is pretty thin, but apparently aspirin inhibits production of prostaglandin D2, a documented mast cell mediator (there are over 200) known to cause vascular havoc.

 

[TreePerson]

Try this:

THE INTERNATIONAL CONSENSUS CRITERIA What is it? Do I fit the criteria?
Posted by MEadvocacy Advisory-Committee 5sc on October 29, 2016

Thanks. They give the same info as ME- paedia which is that only three out of five symptoms required in Section 3. The ME Association also say this.

So the information provided in the chart above is incorrect. Pwme do not need to catch regular viral infections in order to qualify under ICC criteria.

 

[TreePerson]

FWIW, I believe the nano-chip test was only on severe .

They definitely tried it on moderate patients as well. I remember Ron Davis saying in a talk that it had worked on everyone they tried, including more moderate patients.

However in the recent bedside chats with Ben interview, Ron Davis said they had now had one person who didn't cause much impedance to the nanochip. He was considering the fact that this person was taking a number of different medications as a possible reason for this outcome.

It was my understanding that he intended to investigate and test these medicines.

 

[PinkPanda]

I think in order make more progress on Rituximab use in ME/CFS, it would be important to get more knowledge on the possible subtypes of ME/CFS. Of course we'll have to wait till the study is published full, but the main conclusion you can draw seems to be, that Rituximab does not lead to a cure or significant improvement for everyone who has ME/CFS.

There are indications of subtypes in ME/CFS
https://forums.phoenixrising.me/index.php?threads/jarred-younger-on-cfs-subgroups-video.52354/
and if one subgroup has autoimmune disease as a cause and might respond to Rituximab, this might not show sufficiently in a study that doesn't differentiate between subtypes at all.

 

[Woodyrob]

The difference.between the Phase II and Phase III trials is unbelievable. Maybe these Norwegian researchers were just out for funding? It kept them employed for several years. Or maybe they were too honest, I don't know, but I'm sceptical on scientific spin, especially when I see earlier studies looking 'too good'

The BBC Inquiry did a radio program on how many researchers fudged or made mistakes in hast with their data for various reasons.
Many studies published in top journals can't even be replicated. (Not about ME research but you'll be surprised how much trash science gets funded and published)

Is the Knowledge Factory Broken?
BBC Inquiry
http://www.bbc.co.uk/programmes/w3csvsy8

 

[andyguitar]

Looking to Rituximab to provide a cure for everyone with ME or CFS is like supposing other treatments that have helped some will work on everybody. ME and CFS is really just a group of symptoms that the Medics have stuck together to make life easier for themselves.

 

[neweimear]

Looking to Rituximab to provide a cure for everyone with ME or CFS is like supposing other treatments that have helped some will work on everybody. ME and CFS is really just a group of symptoms that the Medics have stuck together to make life easier for themselves.

I totally disagree. It is one disease, we just haven't found a treatment.

 

[unicorn7]

I'm just so disappointed
I don't care about the rituximab or the negative results. I'm very happy that they're doing proper research, no meddling with the facts, not like PACE.

I really thought there was a good chance there would be a good effect in the study and that it would have enormous impact on the medical establishment. Even if it wouldn't work on everybody, it would have put the disease on the map for doctors, pharmaceutical companies, researchers, etc.
The whole argument with the CBT/GET crowd and about the PACE trial would have died in an instant.

Maybe it was just too good to be true It was kind of a shot in the dark.

Moving on... I do think that there will be different groups within this disease. I think the common denominator will be that we all have an acquired functional problem in our mitochondria (as opposed to a genetic defect of the mitochondria). That's the energy/PEM problem. I think the cause and the course of the disease have a lot of difference within the whole group.

I really think the biggest step now, is to find out the most common groups, find a good biomarker for those groups and get on with the research.

 

[unicorn7]

Some good news though...
A slide showed they found p-001 decreases in flow mediated dilation in both RITUXME-baseline patients and pilot patients, and also a prolonged systemic hyperemia response after a POHR-test (http://www.perimed-instruments.com/post-occlusive-reactive-hyperemia)

They ask why? This is normally seen in patients with severe hypertension. Is the NO-production compromised? And by what? Autoantibodies? (which still is possible, there are other autoantibody-producing cells, and it might be going on in tissue too). Other negative bloodflow-regulators in bloodstream? And how does these findings relate with exercise or brain activity, e.g. reading).

Findings yet to be published..

View attachment 25178

I would be very interested in all the things they did find. Do you know when they will come out with these findings?

There is research that has been done on the NO-production.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964747/

 

[Londinium]

They definitely tried it on moderate patients as well. I remember Ron Davis saying in a talk that it had worked on everyone they tried, including more moderate patients.

However in the recent "in bed with Ben" interview, Ron Davis said they had now had one person who didn't cause much impedance to the nanochip. He was considering the fact that this person was taking a number of different medications as a possible reason for this outcome.

It was my understanding that he intended to investigate and test these medicines.

Ah ok, I’m out of date. I just wish they’d go ahead and start formally publishing these findings rather than rely on YouTube updates or similar.

 

[Ben H]

FWIW, I believe the nano-chip test was only on severe patients. But to be honest we have little to go on as it’s not been published in a peer reviewed paper and I will remain wary of the nano-chip findings until it is, so that sufficient detail on possible limitations/confounding factors can be seen.

(Same with the flow mediated dilation stuff above - looks interesting but needs more info, for example on whether sedentary vs healthy controls would give a similar difference).

Hi @Londinium

The nano needle chip has actually been tested on a handful of patients, not all of them severe.

It is preliminary for sure, but just wanted to clear that up.


B

 

[Bander]

Ah ok, I’m out of date. I just wish they’d go ahead and start formally publishing these findings rather than rely on YouTube updates or similar.

That was a long video chat with Ron, but there were useful nuggets in there. He talked about the tension between publication and sharing of ideas. It's best to publish, but that takes a long time. The patient community would prefer to hear ideas right away. The problem with that is that sometimes the ideas are really in the early stages of exploration, so we always have to take all of these comments with a huge grain of salt. In general, I feel that Ron has struck a great balance between keeping us informed of the most promising leads they are pursuing versus sending us off on wild goose chases that might be a waste of our time.

As another example, I was extremely grateful that the negative finding for the Rituximab study was released so quickly. I was on the edge of my seat ever since October rolled around. I was finding myself thinking I had to vow not to read any more Rituximab messages on the forum until the actual research gets published even though that won't be for a year or so. I'm not happy with the finding, but I appreciate that they cared enough to share the overall results early.

Here's another example of how this dilemma plays out. As someone said, Ron mentioned that a patient they tested didn't produce a signal with their sensor and he is wondering whether it's because she is taking a lot of medications. The immediate reaction was, "What the hell medicines is she taking? I want to know NOW." Ron might even regret sharing this tidbit because it was so likely to lead to that follow-up question. I really appreciated the story because it gives me a better sense of what his life is like day-to-day as a researcher, which is the whole point of what Ben is trying to accomplish with this new series. But he should definitely not tell us that list of medications because then we might all start taking the same cocktail "just in case." It's best for him to investigate the lead and report back something more specific if he finds something useful.

 

[Jo Best]

As Ron Davis said at the 2016 Invest in ME Conference, "Cancer is complicated. ME/CFS is complicated".

Olav Mella said at the 2017 Invest in ME Conference words to the effect that it would be surprising if the first couple of drugs they tested for ME/CFS were found to be the best.

Also remember that Invest in ME Research has been funding Jo Cambridge and Fane Mensah at UCL to conduct the B-cell research aiming to be able to identify likely responders to rituximab, adding value to the Phase III trial and preliminary to the UK trial they announced in June 2013 that they were planning in discussions with researchers.

Invest in ME Research commented on Facebook -

We would caution that nothing is certain yet. We hope to meet with the researchers and there are still grounds for optimism. One of the reasons that an early statement was made by the Haukeland team was to avoid patients going for treatment outside of clinical trials and with unselected patients . One of the reasons for the delay in the UK trial of this drug has been due to the desire to find likely responders and it is this caution that the Norwegian researchers have brought out in their results. So we await more news. Stay hopeful until we hear more.
https://www.facebook.com/groups/5804522506/permalink/10155173096892507/

That Facebook post links to their statement: http://www.investinme.org/IIMER-Newslet-1711-03.shtml

We have an excellent research team in Norway which has served the ME patient community and their families with honesty, integrity, professionalism, determination and an empathy which had never been seen before in this field.

We have established good working relationships between the Norwegian researchers and the UK Centre with input from UCL and UEA/Quadram Institute.

We have data now – more than before.

We have research which IiMER has established and a foundation for the Centre of Excellence for ME.

We have international collaboration in research into ME that will continue.

And we have new plans – already in the making.

The researchers from Haukeland will give more detail on their results and publish a paper or two which will benefit all studying ME.

For us, we have invited the Haukeland team to Norwich to discuss the way forward.

We remain positive. Another setback, another day.

We have already been in discussion with our advisors and with the Norwegian team and we will meet to clarify the best way forward in the near future with our major funder and researchers.

We still have much good research being funded and being planned and feel our stategy is, and will pay off and lead to the most rapid route to finding cause(s) of ME and effective treatments.

http://www.investinme.org/IIMER-Newslet-1711-03.shtml

 

[pamojja]

The point I was making yesterday is, there also isn't any hope even with well studied deathly multi-factorial diseases like CVD or cancer. It still can be beat.
...
Sure CVD and cancer patients are more acknowledged, from personal experience the treatment options offered are just as crazy and hopeless most of the time.

I don't know if I get the point. But I would be very happy if I had those "crazy" treatment options like cancer patients...

I'm not keen on the in average of all cancer-treatments possible 3% 5-year mortality reduction, compared to no treatment. And all the devastating side-effects of chemo, radiation and surgery. Of course, there are but only a few kinds of cancer were the chances are much higher. Still, lack of long-term data with a recurring disease like cancer should make everyone suspicious.

And there are "natural" treatment options in lets say cancer with modern studies behind that doctors use... for example high dose vitamin c infusions...

There isn't any successful double-blind study with vitamin C infusions. Just the point I made, there are relatively harmless natural compounds with preliminary findings. Therefore your hospital usually wont apply or health-insurance wouldn't cover.