In this post we will give a introduction of the studyprotocol to the Lillestrøm Health Clinic XMRV study: The Norwegian study of CFS, NO-CFS, Stage 1: Confirmarory stydy for the detection on Gammaretrovirus related Gene Sequensces by Dr. med Mette S. Johnsgaard.
This study is an collaboration with Dr. Judy Mikovits at WPI and Dr. Med. Mauro Malnati at San Raffaele Scientific Institute i Milano in Italy.
The study protocol is released and supervised by Norwegian National Committee for Ethics in Medical Research (REK).
These patients are often given up on by their local GP. Most have been through quite extensive diagnostics without any certain pathological findings. Some have been classified as psychiatric diseases.
A few of these patients do over time recover to a certain degree, but it is very seldom a patient returns to normal life after being so sick. Many barely get out of bed, but function to a better degree. However some patients are bed-ridden for years and years without any sign of any recovery whatsoever.
These patients are often more or less over-looked by health authorities and often no physician has visited them for years. They are often, by family and caretakers kept at home as they are too sick to be able to cope with hospital stressors, giving a huge amount of stress to family who looks alter them, often for years.
In Norway there is no certainty to the number of bed-bound disabled ME/CFS patients, however, we believe to find 50- 100 all over Norway with 20-40 others having recovered to a certain degree.
Information on Lillestrøm Health Clinic:
Lillestrøm Health Clinic in Norway is a private health clinic specializing in the assessment, treatment, and research of chronic diseases such as chronic fatigue syndrome and myalgic encephalopathy/myelitis, chronic digestive problems, fibromyalgia/chronic pain conditions, and more. Medical director of Lillestrøm Health Clinic. Center for Treatment of Chronic Diseases is Dr. med. Mette S. Johnsgaard.
Image: Employers at Lillestrøm Health Clinic.
We work with national and international clinics, specialists and researchers. Our research is primarily carried out in laboratories in Norway, though qualified international laboratories are used when necessary. Our treatments focus on a holistic approach that includes nutritional advice and supplements.
We strive to be a leading institute for the treatment of chronic diseases, especially ME/CFS and fibromyalgia. Through cooperation with national and international researchers and clinics, we provide the best and most innovative services to our patients.
We treat relatives and patients with respect, dignity, and compassion in a safe and secure environment. We promise to give patients the best treatment available.
Research into new and better treatments is an important and integral activity at the clinic.
Our secondary clinic offers private GP services, occupational health and a compliment of services such as nutrition counseling and therapy.
Lillestrøm Health Clinic offers assessment and treatment of patients with individual attention to their situation and needs. Assessments and treatments are constantly changing based on clinical experience at the clinic, research results, and changes in the experiences of our partners, both in Norway and abroad.
Lillestrøm Health Clinic has collected expertise in the treatment of ME/CFS with well-known specialists. We use several types of drugs, in addition to a number of nutritional supplements and diets.
Lillestrøm Health Clinic uses only clinical laboratories that are quality assured. We also provide quick results to relevant tests.
Introduction to the XMRV/gammaretrovirus study:
The etiology to this disease is still unknown. There are different hypotheses including pathogenetic mechanisms within immunology, genetics, virology, endocrinology and even psychiatry. A multifactor etiology has been considered, including both host and environmental factors. There is a need for understanding etiology and pathogenesis, so one can develop biomarkers and diagnostic tests. This Will lead to specific therapeutic revenues.
One of the main arguments concerning etiology of ME/CFS is immune deregulation, often after an external stimulus, often a viral infection.
In 2009 two researchers (Mella and Fluge) at Haukeland Hospital in Bergen, Norway, published a pilot study on 3 ME/CFS patients treated with Rituximab, a B cell depletory. On this background they have a hypothesis concerning ME/CFS being an immunological disease where especially the B cells are involved in the pathogenesis.
This can mean there is a certain autoimmune process going on in these patients. However an alternative theory is that the B-cells are directly involved in a retroviral infection.
In October 2009 a study was published showing the presence of a novel retrovirus XMRV (Lombardi et al (2009), Later studies have not reproduce these findings. New publications are supporting the findings (L/Alter et al (2010), however, the need for a specific PCR analysis (serology and co-culture) for accurate diagnostics seems imperative at this stage.
Project administration and collaborators:
Main Investigator: Mette Sophie Johnsgaard, M.D.
Medical director of Lillestrøm Health Clinic. Center for Treatment of Chronic Diseases, Norway.
Supervisor: Prof. Dr. Med. Ola Didrik Saugstad.
Professor of Pediatrics, Director of Department of Pediatric Research. Rikshospitalet Medical Centre, Oslo University Hospital, Univ. of Oslo. World Renowned d Neonatal Specialist and WHO Advisor, ME lobbyst.
Research: Prof. Dr. Judy A. Mikovits, Whittemore-Peterson Institute (WPI), Reno, USA.
Specialist in XMRV virus, cancer, retrovirology, virology, molecular and cellbiology.
Research: Dr. Med.Mauro Malnati Colleague of Prof. Dr. Paulo Lusso), Milan, Italy
Institute: San Raffaele Scientific Institute, Milano, Italy. In 2001, the San Raffaele Institute was knowledged by the Health Minister as the IRCCS for Molecular Medicine.
Profile: Doctor, researcher and group leader In Human Virology. He is also a top expert in the design and validation of medicular diagnostic assays for human viruses based on Tagman real-time PCR. Deputy Chief of Human Virology at the DIBIT – 5. Raffaele Scientific Institute.
Research: Dr.med. Ingrid Lund,
Lillestrøm Health Clinic. Center for Treatment of Chronic Diseases, Norway
Research: Dr. med. Sigrid Holterman Holmen,
Lillestrøm Health Clinic. Center for Treatment of Chronic Diseases, Norway
There are restrictions with regard to disclosure and publication of the results from the project. It’s written agreement (CDA) between WPI and San Rafaelle Scientific Instiltute (Italy) and LHK regarding this.
The results will be coordinated through WPI.
The project started October 15, 2010, and the first blood samples were sent by LHK at the end of November. The project is expected to end April 30, 2011.
It is not given official government support for the project, mainly financed by Lillestrøm Health Clinic.
Sampling in the United States and Italy, financed by the mentioned research institutes there. Delivery of samples covered by LHK.
Research participants have no financial expenses in connection with the study
Critically ill ME / CSF patients who have an ongoing MLV related virus infection as a guess could be the cause of their condition. Close family members may also have a latent retrovirus infection.
We want to look at the difference between patients with severe form of CFS, healthy families / relatives and healthy controls with respect to the statistical prevalence.
We also want to look at biomarkers of immune dysfunction including cytokineprofile and also the detection of antibody. We believe that it is likely to find biomarkers that can describe and be used for monitoring of the disease.
We think there is a possibility that there are reservoirs of retroviruses in B-cells. This may also explain the positive effect we have seen with the use of the drug Rituximab. Mature B cells that express CD20 in this case must bear the main load of retroviruses. Yet one that whenever an immature B-cells are formed from stem cells in bone marrow and plasma cells as virusload increases and thus the symptoms as the effect of Rituximab decreases.
The main study is ongoing and ends in 2011.
See if the Murine leukemia Viruses (MLV) viruses related Gene Sequences can be found
in extremely disabled patients diagnosed with ME/CFS in Norway.
Look for other characteristics in retroviral cytotoxicity.
Look into disease association and prevalence in healthy relatives and healthy controls.
Look for the major viral load in live PMBC
Look for characteristic cytokine profiles and develop biomarkers for monitoring disease activity.
Patients: The selection of patients included in the study have a known CFS diagnosed according to recognized criteria (Canadian criteria) and who have or have had a greatly reduced level of functioning (KS 40 or lower). Children under 12 years are included in the study. Total n = 29
Selection of control: Selection of control is divided in two, healthy controls with close contact with the patient (family member etc) and a control group of healthy who do not have had contact with the sick.
Control group – healthy family members and any others who have been in close contact with patients: the retrovirus has been detected in people who have been in close contact with patients with ME / CFS (ref Dr. Judy Mikovits). Total n = 15?
Control group – healthy with no contact or connection to patients with CFS: In this control group there will be people who have no connection to ME / CFS or other chronic diseases, as well as not having any kind of accumulation of chronic illness in the family. Total n = 15?
In total, the study consists of 62 participants, of which 29 are patients and 33 controls.
XMRV Blood sampling will be performed through Lillestrøm Health Clinic where that is possible. As many patients live too far away and are extremely disabled, some blood testing will have to be performed through the patients GP. LHK will have to receive the blood sample within 6 (8) hours for preparation. Detailed written information will be sent out to ensecure correct samples.
Immune and regular samples will be send to AHUS, like Hb, Lkc diff, IgA IgG IgM total, IgG subclasses.
Relevant questionnaires in this study:
1. Symptom assessments:
Canadian consensus criteria
2. Assessment relevant to etiology.
The start of symptoms/length of disability
Any relevant disorders before they became disabled
Any traveling: (Asia, Africa, south Europe, South America and North America, special attention to any disease acquired on these travels)
Genetics, how many relatives have autoimmune/chronic diseases
How many children and if or not they have following disease:
Allergies, digestion problems, ADHD, ADD, other chronic diseases.
Degree of self-assessed stress earlier on in life.
Any other relevant information that can explain any triggers, or lack of triggers.
Importance of this study:
It is also important that this patientsgroups has no form of treatment today and we consider it important to explore disease mechanisms to identify potential treatment options. If there are relevant findings in this patient group, we believe it will be used on multiple patients with the same diagnosis but with less degree of disability.
If it turns out that the retrovirus is the cause of the disease, we hope we can get started with studies on relevant medications during 2011. At present there is no approved clinical treatment for MLV related virus infections.
It is a great advantage that the samples are sent to two separate institutes to ensure good test results.
The results from this study will have a great future benefit for patients with this disorder to be taken seriously and get adequate treatment, not only in Norway but around the world with positive findings.
…. And with this I give Dr. Mette and her research team last word!
Read the Study protocol Here: Study Protocol Lillestrøm Health Clinic XMRV_gammaretrovirus NO_CFS stydy Stage one