最新のRituximab Study

・Thu, 6 Jun 2013 14:25:02 -0500

 要約:ノルウェー、Multi-Center、Rituximab トライアル、臨床研究支援基金を受ける

 (注:他のCFS関連プロジェクトも基金を受けた)

 

以下原文:

Norwegian multi-center Rituximab trial receives funding
http://www.forskningsradet.no/prognett-kliniskforskning/Nyheter/Disse_far_midler_fra_Klinisk_forskning/1253987111966/p1228296189450?WT.mc_id=facebook

(Google translate from Norwegian)

Results of the application process:
These are funds from the Clinical Research

Research program for clinical research grant support to ten projects.
NOK 40 million was announced in this application round.

Here is the list of projects receiving funding:

B-lymphocyte depletion with Rituximab induction and maintenance in
CFS/ME. A multicenter, randomized, double blind, placebo-controlled
study.
Project Manager: Fluge, Øystein
Project Owner: Haukeland University Hospital, Helse Bergen

(note: another CFS-related project also received funding)

Irritable bowel syndrome and chronic fatigue following infection with
Giardia lamblia. Premorbid factors and long-term consequences.
Project Manager: Wensaas, Knut-Arne,
Project Owner: Uni Research AS

・Altered functional B cell subset populations in patients with chronic fatigue syndrome compared to healthy controls

http://onlinelibrary.wiley.com/doi/10.1111/cei.12043/abstract
 
 
 

以下、2010-2012年の情報

B-cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Very Severe Chronic Fatigue Syndrome

http://clinicaltrials.gov/ct2/show/NCT01156922

 


Source: University of Bergen
Date:   October 31, 2011
Author: Jens Helleland Adnanes
URL:    http://www.uib.no/news/nyheter/2011/10/solving-the-cfs-riddle


Solving the CFS-riddle
----------------------
For years there has been no cure for chronic fatigue syndrome. But new research in Bergen gives hope to sufferers of the disease.

Two doctors at Haukeland University Hospital have made great progress in their work to solve chronic fatigue syndrome (CFS). Trials cancer medicine has improved the health of two out of three CFS patients. - There is a clear impact. There is hope, professor and senior consultant Olav Mella recently said to Norway's TV2 broadcaster. Mella works at the cancer unit at Haukeland University Hospital, a part of the University of Bergen (UiB). Together with consultant Oystein Fluge, Mella has written a research report in the medical journal PLOS one.

The two doctors have done research on 30 patients with chronic fatigue syndrome (CFS) - or myalgic encephalomyelitis (ME). Half of the patients received a placebo. The other half received the cancer medicine Rituximab. The trials show that the cancer medicine has been very beneficial for CFS patients, according to TV2, and two out of three patients report that they are feeling better thanks to the medicine. The main symptoms of chronic fatigue syndrome are pathological fatigue and malaise after exercise, which does not cease after a period of rest.


Autoimmune disease

The researchers believe that CFS is an autoimmune disease, according to UiB's internal newspaper Pa Hoyden. When patients suffer from an autoimmune disease, the body's immune defence attacks its own tissue. Mella and Fluge told TV2 that their results may be the first step on the road towards discovering a cure for CFS and improve the process of setting a diagnosis. - We will find a cure, Mella said to TV2. - But it may a few years before this treatment will be offered to all patients with CFS.

--------
(c) 2011 University of Bergen    

関連論文(Oystein Fluge, Olav Mella, Cambridge)

http://www.biomedcentral.com/1471-2377/9/28

http://www.ncbi.nlm.nih.gov/pubmed?term=Edwards[Author]%20AND%20Cambridge[Author]

http://www.ncbi.nlm.nih.gov/pubmed?term=Fluge[Author]%20AND%20Mella[Author]



Rituximab study その後、(2012年12月)

Note: Norwegian Health Minister Jonas Gahr Store comments on his
Facebook page about the denial of funds for a Rituximab replication
study. Following is a reply from Barbara Baumgarten-Austrheim on the
issue.

----------------------------------------------

https://www.facebook.com/jonasgahrstore

Today Research announced the projects that will receive funding from the so-called free prosjektmiler. 
Applications for research projectsof pain and / or fatigue symptoms (ME) / CFS did not have funds in this round.

We need knowledge of these disorders that affects many Norwegians. We need serious research.

Therefore, I will in the award letter to the Research Council for 2013 make it clear that research into the causes and treatment of these
disease states will be given priority in research council's program plans. The projects that are not reached in the competition for free
project funding in this round, you will be able to apply for funding under the programs for clinical research, mental health and health
care services research funded through the Health and Human Services Department budget. There will be tendered funds in spring 2013.

In addition, we will continue to grant to RHA West and other regionalhealth authorities for the implementation of the planned multi-center
study on the treatment of ME.

---------------------------------------------

(Google translation)

Dear Jonas Gahr Stohr!

When the first Rituximab study was published in October last year had the great attention both in Norway and internationally. In an article
published on its website TV2 day study was published, 20.10. 2011, one can read the following: "- This looks very promising. From what I
hear, this is perhaps the key for many, Strøm-Erichsen. "

"- If this can help to make many healthy, then it's absolutely amazing, says minister having seen the feature from TV 2. She promises
to follow up the breakthrough that has given new hope to millions of CFS patients. "

Later it was allocated two million from the state budget for further research on Rituximab (only medicines in a follow-up study costs over
eight million), was modest further that research had to be soughtthrough the normal channels, ie NFR and RHF'ene. Everyone knows that
only a fraction of the projects that are seeking funds and this procedure has delayed a follow-up study is necessary to know whether
the findings of the first "small" double blind study is to rely on, with at least one year. When the study so far have not received funds
will reference to new applications in earmarked funds delay trial with at least nine months.

Professor Mella and Dr Fluge is very sober researchers note that the findings of a relatively small phase 2 study must first be confirmed
in a larger Phase 3 trial, before one can recommend a treatment.
Doctors who work with ME patients in other countries are often not equally sober. Both in Germany and the USA, there is fremståede
doctors who work with patients with ME who begin to treat these patients with Rituximab only of double-blind study that was done on 30
patients. Several patients have already approached me, asking if I think it is wise that they travel to the U.S. for treatment, something
I have dissuaded because I support Fluge and Meller attitude that we need at least a larger study to confirm the findings .

In Norway, we have very conservative estimate, based on the most stringent diagnostic criteria, between 5500 and 10 000 patients with
ME. All these are, at least partially disabled and depending NAV benefits. Many of them for many years, or for life. These people can
not pay taxes, but on the other hand needs to receive benefits.

According to figures from Statistics Norway Average wages in Norway in 2011 453.000 million, between 30 and 40% of this goes to the
government in form of taxes. If we assume that each ME sick on average receive benefits equivalent to the minimum in 2011 was about 164 000
needed only 30 CFS patients' return to work to pay it Fluge and Mella're about NFR, to conduct multi-center study in which 140
patients with ME are included.

In this study, 70 patients receive Rituximab and 70 will receive placebo. If the response is in line with that seen in the study from
last year and that one still sees the ongoing pilot study 46 patients will be significantly better. If one assumes that only 2/3 of them
come back into the workforce, these alone have funded the study during the first year of the job!!
ME affects mostly women and onset usually in the age group 20 - 40 years. These patients lose important years in their life, they lose
the opportunity to get an education and many lose the ability to have children. Here we talk about the many lost years of quality of life
and ability to contribute to society, for every year a Phase 3 trial is delayed.

As long as there will now be earmarked funds for MOH which will then be distributed by application and we know that there is no one else
who can carry out such a study, I have one prayer: Please, Jonas, skip one delaying bureaucratic joints and increase budgetary allocation
from two to nine million, so the study could start in January!
Patients have waited long enough!

Sincerely, Barbara Baumgarten-Austrheim, outgoing Head of ME / CFS
Center, Oslo University

For more info on conference plus links to conference videos-
https://listserv.nodak.edu/cgi-bin/wa.exe?A2=CO-CURE;919c41c3.1210A

------------------------------------------------------------------------

http://rme.nu/sites/rme.nu/files/1_6_miljoners_nr4_2012.pdf

1.6 Miljonerklubben Nov. 4, 2012


Joy Notification by Professor Olav Mella:

Cancer medicine gives ME/CFS sufferers hope!

Cancer medicine Rituximab, according to a Norwegian study published in 2011, led to improvements in two of three patients with the
neuro-immune disease ME/CFS (chronic fatigue syndrome).

Now a follow-up study that the effect is also considerably more prolonged than had previously been seen. This statement gave joy Olav
Mella, a professor at Haukeland University Hospital in Bergen and one of the researchers behind Rituximab studies, in a speech at a
well-attended ME/CFS conference in Stockholm early last fall. The results of the current study is unpublished, but the preliminary
findings are clear, according Mella. Has already been seen that drug Rituximab helps with ME/CFS, in isolated cases, a dramatic improvement
has been observed. Now we can see that the preparation has benefits for the long term. However, he is still secretive about the details of
the current study, expected to be published during the first half of 2013.

28 ME/CFS sufferers treated with Rituximab in the ongoing follow-up study. They get six infusions over a 15-month period, compared with
the old, placebo-controlled study, in which two infusions were given for 14 days, and patients were then observed for one year. The
previous study, published in the prestigious scientific journal PLoS One, 2011, gained international attention and gave ME/CFS sufferers
worldwide hope for a future effective treatment for the disease.

Rituximab suppresses blood B lymphocytes. The research team Olav Mella and Oystein Fluges findings indicate that there are autoimmune
components linked to ME/CFS. At the seminar in Stockholm also appeared Professor Christopher Snell from Pacific Fatigue Laboratory,
California, who has studied in one of the main symptoms of ME/CFS, namely deterioration after exertion. It is well known that ME/CFS
sufferers exhibit worsening malaise and general symptoms increase even after relatively little effort, and it requires at least one day of
recovery afterwards, sometimes considerably longer, depending on how sick you are and how much overworked himself. That's why ME/CFS
sufferers can not train themselves to a better functional capacity.
The deterioration is often a delay of several days.

Christopher Snell's published research showing by objective markers that ME/CFS sufferers become significantly worse during cycle tests
repeated after two days. He has also shown that this deterioration is different from the fatigue that can be seen after repeated stress in
healthy people and in people with other diseases. The most important measurements are aerobic capacity and oxygen uptake at the so-called
anaerobic threshold. The results are an important piece of the puzzle for the understanding of ME/CFS.

The seminar also appeared Per Julin, chief physician for ME/CFS project at Danderyd Hospital, who presented the project experiences to
date, and Professor Kristian Borg, Department of Clinical Sciences at Danderyd, who pointed to parallels between ME/CFS and post-polio
syndrome.

The seminar was held in a crowded county hall in County Hall in Stockholm, and was organized by the National Society for ME patients'
local union in Stockholm in collaboration with the Adult Education Association. 131 listeners had flocked to the seminar, including many
nationally leading researchers in the field, as well as doctors, government officials, and of course patients and relatives.

MORE ABOUT ME/CFS

ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), previously known as chronic fatigue syndrome. The disease affects men,
women and children. Most common age at onset is 30-50 years. More than 70% are women. Nearly 40,000 people in Sweden is estimated to have the
disease. It is therefore more common than some other neurological diseases such as MS and Parkinson's. The onset usually occurs suddenly
and symptoms are many. Fatigue, even after small effort, sleep problems, headaches, muscle and joint pain, fever, sore throat, memory and concentration problems, confusion, sensitivity to light and sound,
dizziness, indigestion etc.

The cause is unknown. Triggers can include: infection, often flu-like, recent vaccinations, surgery, physical trauma, environmental toxins,
etc.. There is no cure for ME/CFS, only palliative treatments. Less than 10% are healthy. Besides clinic at Danderyd, is just another
specialized unit for ME/CFS, namely Gottfriesklinien in Mölndal, which receives patients from Västra Götaland and Halland. 17 of 20 counties
is therefore without such receipt. Research on ME/CFS is conducted primarily in the U.S., UK, Japan, Belgium and Australia. Patient
Association RME's website: www.rme.nu

The article below was published in Norway's biggest print newspaper, A
magazine, on Dec. 14, 2012. (Google English translation below)

---------------------------------------------------------

A Magazine Dec. 14, 2012

Original text (in Norwegian)-
http://me-foreningen.com/meforeningen/innhold/div/2012/12/ME-A-magasinet.pdf

Hopes on a miracle
Desperate Norwegians travel to California for treatment-with same
cancer medicine looks to cure CFS patients in Bergen.


Maria Gjerpe is 44 years and has had ME since she was 16. For just
over a half ago she lay under the covers 21.5 hours a day. Now she
sits full of pep at Haukeland University'cancer ward. In the hand, she
has a cannula in face a wide smile and eyes that glows. Beside her
stands chief Øystein Fluge and oncology nurse Helle Øvrebø. Rarely do
they see so striking transformations in patients.

- When you came here for the first time in April, it was as far as we
got up from the wheelchair to the bed. You were shaky, unwell and very
difficult to talk with, recalls Øvrebø.

- I hardly remember it. All that concerned was to survive, replies Gjerpe.

This is the fourth time she's in Bergen to be given the cancer drug
Rituximab. Earbud and the dark sunglasses she wore on her first,
exhausting journey from Oslo, she long since put away.

- How's it going? ask Fluge

- I must exert myself for not only a grin: I am perfectly well!

- How is your activity level?

- I go for walks in nine miles, without break and without getting
tired. I read, lectures and writes feature articles, reply Gjerpe
proud. In better times she has been able to train as a doctor, but it
took her 12 years.

- There is no longer any doubt: You approaching complete response to
medicine, concludes Fluge, while Nurse Øvrebø almost feel honored.

- I did not like this was possible. It's incredibly nice to be with
when people get their lives back. I had no idea that so many suffered
so terribly with ME, she says.

STUMBLED INTO. It had no powers over Øystein Fluge and his colleague
Professor Olav Mella either, until they observed something surprising
in 2004: A woman with ME had lymphoma and was treated with four
different chemotherapy regimens. Six or seven weeks out of one of
them, she was suddenly temporarily relieved by ME symptoms.

Doctors analyzed cell poisons she had received and decided that it was
probably a drug that affects B-cells (a type of white blood cell),
which had had the unexpected effect of ME disease. After she recovered
from cancer, why they chose to give her the cancer drug Rituximab,
which targeted reducing the number of B-cells.

Mella and Fluge knew that Rituximab also be applied to autoimmune
diseases such as rheumatoid arthritis and lupus. Could it be that the
"mysterious disease" ME belonged to the same category?

Having seen the response in another two pilot patients, implementing
the a small, double-blind study. 15 ME patients received within 14
days two infusions of Rituximab, as many received only saline
(placebo), and neither the doctors nor the subjects knew who got what.

The results of the study were published in the medical journal PLoS
One last fall and attracted attention world over 10 of the 15 who had
received Rituximab, were significantly better. But jubilation over the
breakthrough was not unanimous.

SHOCK. Ignite a peppery, roll in a minefield and pour gasoline on the
fire. About as explosive, the Norwegian ME debate.

In one corner: those who believe ME / CFS is a psychosomatic illness
that can be cured with cognitive techniques such as Lightning Process
(LP) or mindfulness. In the other: those who argue that ME is a
clearly defined physical diagnosis that will be cured as researchers
find biomarker and forensic medicine.

Duellantene lashed out swing punches to beat counterpart knockout.
With the imminent danger to frame even those who have inadvertently
ended up somewhere in the middle.

People like Mella and Fluge.

- Our field is cancer. We had no idea how inflamed ME discussion is.
Fasten a ME conference in London sat patients and hollering and
whistling at debate panel. That aggression is not exactly accustomed
to cancer conferences. But there also experiencing the patients to a
greater degree to be taken seriously, says Mella.

- I stay away from all the noise on the Internet, avoid google ME and
chronic fatigue syndrome.

War of words is just distracting. I understand why we are taken to the
income a purely biological view, but that is to underestimate us. The
psychic and the physical hangs course together, says Fluge.

CALIFORNIA DREAMIN '. After their study became known last year, Fluge
Mella and received over 500 inquiries, many of them utterly
heartbreaking, from ME sufferers who desperately want to try
medication.

- I am almost sick when I read. It is lidelseshistoríe by
lidelseshistoríe, but it gives inspiration to work on this, says
Øystein Fluge.

Some medicine he can not offer those who contacts. It can, however,
the American physician Andreas Kogelnik at the Open Medicine Institute
outside San Francisco. He has begun to accept Norwegian CFS patients
for examination and treatment.

- We have been contacted by over a dozen Norwegian patients, and a set
of them are now participating in our studies, says he to A magazine.

One of them is "Maya". She lives in Oslo Area, is 28 years old, has
had ME since she was 16, and the last four years the disease has taken
over her life. She is partially disabled, has at times been in need of
care, and she knows that for every helpless today as yesterday, be
more dreams in ruins.

She believes that medicine made her a little better, but that the
effect slackening journey is so insanely exhausting. In January, she
travels back in the wheelchair and companion, for another infusion.

 - I have to pay for this with loans all sides, which puts me in a
future financial difficulty. I no guarantee that the treatment going
to work, and it is therefore an immense physical strain to travel so
far. Yet I have not really been in doubt. I think no one in my
situation would have been.

 For not only is life put on pause; she also fear being regarded with
suspicion at all levels, that many believe she only makes itself. It
is not to endure.

 - I can not let this stand untested. For the chance to get myself and
my life back, I am willing to sacrifice everything.

FRUSTRATED. In Mid-Norway live "Unni" another of Kogelnik's Norwegian
patients. When Fluge and Meller study published last fall, was
23-year-olds hope. That soon was turned to frustration.

 - To know that there was a medicine that might help me, but I at best
to wait for several years to make, was cruel. I want the to live a
life now!

At Christmas last year, she started and family to probe the
possibility of â Rituximab get outside Norway. They knew it would cost
enormously, both of money, time and effort, but decided to let it rip.

 - For me it would have been luxury to take the mail without any
problems. At times I have to lie down and recuperate for â grab a
glass of water. Travel to California seemed impossible. In addition
did we that I could end with no response or with serious side effects.
Yet I decided to try.

So far she has been three times in Kogelnik. Without getting better.
The last month is she on the contrary become much worse.

- It's awful tough. I do not know about deterioration due to
medication. But I try to keep up hope.

The next visit is scheduled for January. The family has already spent
over 200,000 dollars on travel and treatment. Unni knows she is lucky.

- There will be a class distinction between ME patients either alone
or with family's assistance may buy assistance and those who can not
afford. I think it is incredibly unfair.

NOT MYSTERIOUS. Since the first study of its fame in October, have the
verbose enthusiastic Bergenser Fluge and Mella, which carry serenity
of his home district Kongsvinger deep forests, conducted a open-label
study of 28 patients who know that they receive Rituximab.

The results are not yet published, but at conferences, there have been
shows that also in this study, approximately two of the three
participants significantly response. Kogelnik report corresponding
payout on their patients, and says that he is now of organizing a
double-blind and placebo-controlled Rituximab study at six or eight
international research centers.

- I will get back to coordinate with Fluge and Mella, he assures.

Meanwhile, only two of the ten recovered in Fluge and Mella's first
study avoided relapse. Much suggests therefore, the medication must be
taken over a long time, as it is used by people with arthritis.

- If the ME is an immunological disease, so we believe it will be the
rule, says Mella.

But this is also a disease that can be cured with mental coping
techniques? Mella and Fluge invalidates no experience of ME sufferers
who after three days of Lightning Process Course gets up from the bed
and declares healthy, but tries to balance them against their own
Rituximab studies.

Their theory is that CFS symptoms not always directly caused by the
underlying disease.

- We know that especially in the frontal lobe brain through very
active thinking can affect and suppress the involuntary nervous
system. That's probably a major reason for the LP and other extreme
forms of cognitive treatment can provide as rapid effect. For some
lasting effect, and then probably the underlying disease state "Burned
out." In others effect of such techniques are at best transient. When
we believe that the underlying cause, the disease state, probably
still present, explain Mella.

NOT EXPERTS. Many other question remains: Why respond some of
Rituximab after six weeks, others for six months? And what about those
who do not have known effect at all, neither in the first or second
trial?

Plays possibly immune system T-cells a larger role than B-cells with them?

- We try not to appear to be experts on ME. Both our studies has clear
weaknesses: The first was small, the other is open and without the
placebo group. But we are quite confident that we have fallen into
something that is true, says Mella.

- A mysterious illness is not. When their mechanisms underlying
available, we think, of course, that's it! For we know that Rituximab
works, what remains is to find definitive answer as to why, adds
Fluge.

COLLECTION. That's why searched the Research Council for nine million
to implement a large, double-blinded and randomized national study in
140 ME patients next year.

Last week came the answer: 34 projects of more than 400 applicants in
health, medicine and biology were awarded a total of 234 million.
Mella and Fluge were not among them.

The reactions were not long in coming. Patients and families
desperately, Ema Solberg called the decision sad, both Maria Gjerpe
and ME Association announced that it would start rolling penny, a
upset Laila Dâvøy (KrF) rushed right the Parliament's rostrum and
demanded that the government immediately allocate 9 million, and
Health Minister Jonas Gahr Støre expressed surprise the Research
Council's decision, however, without giving binding promises.

The only ones who seemed to make the decision calmly, was Mella and Fluge.

- It actually came as no big surprise. There were many very strong
candidates, and we had under 10 percent chance of getting a yes. But
we continue to plan our study. I'm sure there will be funds
eventually. There is appropriated two million both this year and next
year budget, and with time we will have accumulated enough money. For
Fluge and me this is not a tragedy. But it's a pity for the patients,
said Mella.  oIa.henmo@aftenposten.no

------------------------------------------

Zumba Dancer

Lene Loe (39)
Married, two children

I've had ME since 2007. When I got the offer to participate in the
first study to Mella and Fluge, I lay in my room, full of anxiety,
despair swell. They could offered anything.

I had nothing to lose.

As month after month passed without any thing happened, I was sure I
had received placebo. But then. After about six months, it began to
ease.

It lasted not. One year after infusion, I was almost back where I
started. Fortunately I got Rituximab again from the autumn of 2010,
and experienced exactly the same: After six to seven months I was
better. I, who had not been in town for years, endured the sudden both
light and sounds.

Now I have received infusions of between three and six month
intervals, the last in February, and shape improvement has been
remarkable. I am back at work as a teacher, zumba dancing and going to
yoga. I have nearly repressed how sick I was.

----------------------------------------

Up and down and up and down and up

Mariann Ripel (41)
Married, three daughters

- I was one of those who received Rituximab in Mella and fly first
study in 2008. The effect came after just seven weeks. I got better
and better. Started to go for walks and socialize. It lasted approx.
six months.

Then it turned.

In 2009, I join the second their study. The same thing happened this
time, but now I got multiple doses, and progress only continued. In
January 2011, I received the last dose. Then I had ten months without
recurrence. So said the pang.

Within two months I was back in the bottom.

In January this year, I luckily be the pilot for the next trial, and
history has repeated itself. It is just not possible to say that this
is a coincidence. Now I work 40 percent as a nurse and has begun to
further study to be a nurse.

The way it looks now, I can not continue on the medication forever. I
hope that the disease burns out, and try not to think that I can get a
new relapse. No one knows what the future holds, I can in a car
accident tomorrow, and I refuse to take your sorrows in advance. I
have one infusion again. After that I have at least ten good months to
look forward to. Those I enjoy.

-----------------------------------------

Newly saved

Hanna (30)
Married

When I was in the first study, I slept up to 20 hours a day, was dizzy
and nauseous. I had a huge hope that medication would help, but knew
that it was 50 per cent chance that I was given medicine without
substance. Then after a year I was informed that I had received
placebo, I was so happy. Then I knew you it was still likely that the
medicine would work on me.

I got to be involved in the maintenance study in 2010. Mella and Fluge
said it probably would not take long before I noticed any response, so
I was not really waiting, but after infusions in October and November,
I knew that something was happening in the body. Suddenly, I was
refreshed after sleeping. After a few weeks I asked my husband if we
were to walk, and so it has continued.

I will say that I'm 100 percent healthy. I have finished Master degree
gave-my friend and is working full time, but I have not told about the
disease to my bosses. I fear that it will cleave to me if I seek new
jobs. Therefore, I will remain anonymous in A magazine well. There are
many prejudices ME. Many people think that it is really just to pull
himself together.

I can only imagine how painful it is to read about people like me, for
those who do not get medicine. I've got my life back and hope that
everyone gets this chance. I seems certain newly saved, but it's so
wonderful to live and work normally. Now I've been healthy for two
years. I am no longer afraid of relapse. This is going to hold.