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Norwegian rituximab study to start 2014

Ninan

Senior Member
Messages
523
http://mariasmetode.no/2013/11/update-haukeland-english/

12 fresh millions for the Rituximab study

The Stoltenberg administration (the former Government) did propose a continuation of the economic support to the studies of CFS/ME by Helse Vest. Helse Vest have been granted funds for a national clinical multi centre study of CFS/ME both in 2012 and 2013. The proposal is to continue the support pursuant to cap. 781, post 79. This is understood to imply that the two millions that are now granted by the government budget are for the Rituximab study at Haukeland Hospital, as the four millions that have been granted over the government budget at an earlier stage. There are no comments or signals that indicates otherwise. This means that in total six million NOK have been granted over the government budget.

Last week, the news was out that The Research Council had finally decided the spesific number of their contribution to be 10 million NOK. That means that it´s now 19 million NOK for the multi center Rituximab-study. 10 from The Research Council, 3 from MEandYou and 6 through the governmental budget.

Multi center study
The coming study is a multi center study. This means that several centers will, in accordance to a common protocol, treat a predetermined number of patients with Rituximab to study the effect. The datas with the results will be collected and treated at one location, with the participation of, and transparent to, all participating centers

Where will the studies take place?
As of today there are five centers that each will be in charge of a group of patients. Who will be part of the groups, and how many patients at each location, have not been decided yet. The locations are Oslo, Trondheim, Notodden, Tromsø and Bergen

When will the studies start?
When the studies will start at the various locations have not as of today been decided, but most probably during spring 2014. The researchers are in contact with each other and are doing the final work on the protocol for the study, in addition Forskningsrådet have not yet decided on how much their contribution to the study will be

What is a protocol?
A protocol describes in minute detail how the study is to be carried out. That the protocol is thorough and closes any holes that can be questioned at a later time are of uttermost importance. This takes time – but it pays to wait a bit extra to achieve a solid study that produces valid results

How many have applied to take part?
Don´t write more letters! We have received more than a thousand letters and referrals. So many, that it have been impossible for the researchers to reply individually. Your letter has been read even if you have not received a reply. All applications have been read, roughly classified by region, and will be forwarded to the nearest of 5 institutions

How many patients are needed?
It looks like 144 of this 100 will participate in the study. Half of these will receive medication, and the other half salty water (this is called placebo).

Who will be selected?
The decision is made by the institution as long as it is within the numbers that have been agreed upon. All the selected patients have to qualify according to the Canadian criteria, and have to be residents of Norway. Patients that have received Rituximab at an earlier time can not take part in the study. Although all the patients will be Norwegians, the results and knowledge found in this study, will be of benefit for both patients and doctors abroad.

What happens with those participiants who do not receive medication?
Half of the participants will not receive medication, but a small dose of salt water. This has no effect on the disease itself. At the same time we know that ME, over time in some patients, will improve without treatment. We want to control for this effect by the use of a placebo group in the study. If it turns out, after the study have been analyzed, that Rituximab have effect, and the cost of medications can be covered. those who received salt water will get Rituximab, possibly in a new study. That may only take place when the current planned study have been done and analyzed. This might take three years

How will I know if I have been selected?
Those who might be candidates will be contacted when the day of selection approaches. Then you will be called in for a pre-examination, then you will be notified whether you are selected or not

Do we need more studies after this?
For a medication to be approved for the use for a specific disease the use must be approved by «legemiddelverket» in Norway, and/or FDA in the US. If the result of this study turns out positive Rituximab will be much closer to approval. Whether the study is enough depends on the quality of the protocol – and consequently how reliable the result is. This is one of the reasons for the time and work spent on the reliability of the protocol.

How much time before we might receive treatment with Rituximab?
First all the patients have to go through the study, this will take two years starting when the last patient is included. All data will then have to be controlled, analyzed and published. FDA and the Norwegian «Legemiddelverket» will evaluate the data and decide wether there may be a new indication for Rituximab. This will at least take 4 years, possibly more. Rituximab will certainly not be a medication for all ME patients. As with any kind of illness or condition it is probable that different ME patients need different kind of treatments and medication

Work is done on symptom directed treatment
Do not despair! The researchers are aware of how horribly ill patiens are and how difficult life is for ME patients. Intense work is done paralell to the rituximab study to find symptom directed treatment for the patients as patients. Several different medications are being tried.
 

Seven7

Seven
Messages
3,444
Location
USA
that's exciting!

however, saline is not placebo in ME.
HOLLY C! good point, giving me Saline once a month would be enough to improve like 3 to 4 points for me!!!! Even though they say a small doses. If it is a few CCs might be ok.
 

Ninan

Senior Member
Messages
523
Saline once a month does nothing for me or anyone of the ones I know who have tried it. Dr Bell says so too. Must be at least three times a week to make any difference for me. There are probably exceptions but for most PWME:s the dose they give shouldn't make a difference.

And yes, it's great news! :)
 

CBS

Senior Member
Messages
1,522
Saline once a month does nothing for me or anyone of the ones I know who have tried it. Dr Bell says so too. Must be at least three times a week to make any difference for me. There are probably exceptions but for most PWME:s the dose they give shouldn't make a difference.

And yes, it's great news! :)

Glad to see this moving forward. I agree that saline in ME patients is not a placebo. Whether or not it would effect results will depend upon the amount of fluid given and the timing of functional testing and collecting reported activity/symptoms relative to the time of the infusion.
 

Ninan

Senior Member
Messages
523
Since the amount of fluid given should be the same in both groups there shouldn't be a difference in response. The researchers are aware if it so I can't see it distorting the trial in any major way. There is no alternative, that I can think of, anyway.

Anyway, we're up for at least six years of waiting. I hope that Roche and the others are pickning up and doing their own trials when they develop the successors of Mabthera. There are many new meds like it coming.
 

CBS

Senior Member
Messages
1,522
Since the amount of fluid given should be the same in both groups there shouldn't be a difference in response. The researchers are aware if it so I can't see it distorting the trial in any major way. There is no alternative, that I can think of, anyway.

I agree that there may be no suitable alternative to using a saline based placebo but I'm less comfortable assuming that there is no potential for significant issues with doing so. Comparisons between groups should remain valid but comparisons to baseline may dismiss some degree of improvement as "regression to the mean" if saline used as a placebo has a therapeutic effect. This is where good design and awareness of potential issues become essential.
 
Last edited:

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Lets look at it this way. Saline is mildly to moderately beneficial. Using that as the control means if they get successful results then they would be really good results. If however Rituximab gets dismal results, it will help to discredit the research. I do not think this likely however, from all reports the phase 2 trials were quite successful.

They don't have many choices however. They need to deliver a liquid control comparison. They cannot use just distilled water as it might induce electrolyte problems. Saline is about the best they can do I suspect.
 

Legendrew

Senior Member
Messages
541
Location
UK
Lets look at it this way. Saline is mildly to moderately beneficial. Using that as the control means if they get successful results then they would be really good results. If however Rituximab gets dismal results, it will help to discredit the research. I do not think this likely however, from all reports the phase 2 trials were quite successful.

They don't have many choices however. They need to deliver a liquid control comparison. They cannot use just distilled water as it might induce electrolyte problems. Saline is about the best they can do I suspect.

Exactly - criticizing the use of saline as a control is fairly ridiculous, more questions would be raised if it wasn't, given that saline is the standard control in medical trials of this nature. I admit that saline may be slightly beneficial for those who suffer low blood pressure and have ME associated with POTS or OI, however, if anything but saline was used I suspect it would be picked up on and used to criticize the design of the trial.

That said I look forward to the results of this trial in a few years time!
 

aimossy

Senior Member
Messages
1,106
All I can say is thankyou Norway and YAY.
This could turn out to be the turning point in ME history....I hate to think what if they thought nah lets not bother about this thing that was noticed.....how much longer could we have been waiting for this to have perked doctors interest......fingers crossed and another YAY.
 

Ninan

Senior Member
Messages
523
I wonder which other meds are being tried. I would guess gammaglobulin is one of them. And they are using Enbrel for patients who don't respond to rituximab.
 

Ninan

Senior Member
Messages
523
Any improvements from the saline would be short lived anyway. im guessing the rituximab infusions are given weeks or months apart. for saline to have an affect one would need saline infusions atleast twice a week??

Three times a week, in my case. Dr Bell says once a week makes one good day and six bad days.
 
Messages
15,786
Saline is an appropriate placebo. Rituximab is given as an IV fluid from what I understand, so the results patients experience are from the drug + the fluid increase. By just doing a fluid increase in controls, it's accounting for the effect of the fluid increase in Rituximab. Thus the actual improvement due solely to the drug can then be determined.
 

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England

Firestormm

Senior Member
Messages
5,055
Location
Cornwall England
From what I've read (I'm Swedish so I read Norwegian) they seem to be pretty ambitious. They know they'll scritinized, big time, whatever the result.

I am of the opinion that fair scrutiny is needed. I want all ME research to be put under the microscope so that there can be no doubts. I recall well the 'arguments' put forth in the comments on PLOSONE I think it was when the orginal study was published. The Norwegian doctors were excellent in their rebuttal. My fingers are crossed that this forethought with regards to outcome measures means a better all round result for the study.
 

Persimmon

Senior Member
Messages
135
They're using the CCC!

When Fluge & Mella conducted their initial blinded RCT, they used Fukuda.

Possibly the decision to use CCC this time is driven by ethical constraints - who would sit on the ethics board and risk approving the administration of Rituximab, a potentially deadly drug, to fatigued individuals who don't have a disease?

Another possible motivation for the change is that CCC presumably gives Fluge & Mella a better chance of clear-cut positive results.

A third possiblility is quality control. No doubt Fluge and Mella selected patients carefully in their prior studies - picking genuine ME patients from among those who met Fukuda. This time, each trial centre is to independantly assess potential participants within its geographic catchment area. Using CCC would give Fluge and Mella a greater assurance that all the study centres will be selecting suitable cohorts.

Whatever their reasons, they are voting with they're feet and bypassing the HHS/IOM circus!