The PACE Trial UK M.E./CFS Research Collaborative XMRV Research Rituximab Trial UK ME-CFS Biobank The Microbe Discovery Project Right Arcuate Fasciculus Abnormality Blood Biomarkers
Latest Research Participate in Studies Useful Links
Research into the cause and treatment of Myalgic Encephalomyelitis (M.E.), or Chronic Fatigue Syndrome (CFS), is under way in many medical centres throughout the world. Here you will find a summary of past and present research, along with information on how to follow or participate in the very latest studies.
The PACE trial was a five-year £4.2 million study, funded by the Medical Research Council, Department of Health, Department for Work and Pensions and the Scottish Chief Scientist Office. The therapies tested were Cognitive Behaviour Therapy (CBT), Graded Exercise Therapy (GET), Adaptive Pacing Therapy (APT) and Specialised Medical Care (SMC). Participants were referred from six specialist hospital M.E./CFS clinics in Edinburgh, Oxford, Bristol and London.
The results were published by The Lancet in 2011, and concluded that CBT and GET were each "moderately" effective compared to SMC alone, while APT was not found to be effective when added to SMC. Patient groups and the International Association for CFS/ME have criticised the trial for over-simplified and exaggerated conclusions, for using a flawed psychosocial illness model that ignores biological evidence, for testing a non-representative version of pacing, and because the results seriously conflict with their member surveys which show that pacing is effective and CBT or GET can cause deterioration in many patients who use the treatments.
On 21 October 2015, journalist and public health expert David Tuller published the first instalment of a three-part series re-examining the trial. Trial by Error highlights serious flaws in the PACE trial’s methods and says that top researchers whom he interviewed confirm that the study is “fraught with indefensible methodological problems”. He reports that the study’s measurement methodologies changed partway through the trial and that all four of the criteria for recovery specified in the protocol were abandoned and replaced with weaker criteria. Although the PACE researchers declined David’s efforts to interview them, they subsequently requested the right to reply and defend their findings. This issue received press coverage and patients gathered more than 10,000 signatures on a petition to The Lancet demanding action. The experts Tuller quoted, concerned about the PACE study’s unacceptable flaws, signed an open letter to the journal and its editor, Richard Horton, seeking an independent review of the trial data. You can follow this ongoing story in the News section on the right-hand side of your screen.
Under the chairmanship of Professor Stephen Holgate, and expert multidisciplinary group was set up in 2008 to examine and advise the Medical Research Council (MRC) on the current state of M.E./CFS research. The group finished its work in 2012; their findings and recommendations can be read at www.mrc.ac.uk/funding/science-areas/population-systems-medicine/cfsme.
The following year, members of the MRC Expert Group set up a UK M.E./CFS Research Collaborative (CMRC). The aim of the CMRC, which is the first of its kind in the world, is to promote the highest quality of basic and applied evidenced-based and peer reviewed research into M.E./CFS. It brings together national agencies, M.E./CFS charities, and working researchers from across the UK who wish to work towards that common goal. The CMRC held its first annual science conference in Bristol on the 1st-2nd of September 2014. Last years conference brought together more than 90 researchers from Norway, Belgium, Australia, New Zealand, the US and the UK, plus 50 people affected by M.E., carers and advocates. CMRC conference reports, along with the minutes of CMRC meetings, are available to download from Action for M.E.
Xenotropic Murine Leukemia Virus-Related Virus, or XMRV, is a retrovirus that was first identified in 2006 in tissue samples from men with Prostate Cancer. In 2009 a study by Lombardi et al. reported XMRV DNA in 67% of people with M.E./CFS, but in only 4% of healthy controls. The authors reported that patient-derived XMRV could infect cells in vitro, and stated that "These findings raise the possibility that XMRV may be a contributing factor in the parthenogenesis of CFS." The report published in Science generated worldwide media coverage and subsequent conflicting study results.
Independent laboratories from around the world have not detected XMRV in M.E./CFS patient groups or control populations, using blood samples or cerebrospinal fluid. Various PCR (Polymerase Chain Reaction) assays and antibody-based detection methods were used in these investigations. Some of the authors of the original report suggested that the widespread failure to replicate their results was attributable to different PCR conditions, or to different criteria used to classify patients. However, several negative studies have been conducted with the same PCR primers used in the first investigation.
In June 2011 the Editor-in-Chief of the journal Science published an Expression of Concern, stating that "the validity of the study by Lombardi et al. is now seriously in question". In September 2011 the original authors published a Partial Retraction of their 2009 findings, in which they acknowledged that "some of the CFS peripheral blood mononuclear cell (PBMC) DNA preparations are contaminated with XMRV plasmid DNA". A full retraction was issued by Science in December 2011; read more at
An international workshop was convened in September 2010 to aid in resolving the discrepancies. At the meeting, it was announced that Dr Ian Lipkin would oversee a multi-centre trial that would culminate in blind testing of 150 M.E./CFS patients and 150 healthy but comparable donors by laboratories at the Whittemore Peterson Institute, the National Institutes of Health and the Centers for Disease Control and Prevention. The results of this trial were made available in mid-2012, and concluded that XMRV was not present in either M.E./CFS patients or the control group. The study can be read in full at
Rituximab, chimeric anti-human CD20, is approved for treatment of B-cell Lymphoma in adults. It is being used experimentally in various other immune-related diseases, such as Immune Thrombocytopenic Purpura, Systemic Lupus Erythematosus, Myasthenia Gravis and Rheumatoid Arthritis.
In 2009 a preliminary study from Norway suggested that Rituximab could help patients with M.E./CFS; Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series. The same group carried out a double-blind, placebo-controlled study in 2011 which produced a significant clinical response of those receiving active treatment; Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study. The findings received extensive media coverage, and the Norwegian Research Council announced funding for a Phase III study. The three-year study started in May 2014 and will end in December 2017; please Click Here (Norwegian) for more details.
As a result of the Norwegian study, the charity Invest in ME is currently raising funds for a trial for Rituximab on adults in the UK; please visit www.ukrituximabtrial.org for further details.
Building on feasibility studies, the UK ME-CFS Biobank project set out to establish the UK’s first biobank of biological samples for research on M.E./CFS. The project launched in 2011 with the support of Action for M.E., the ME Association, and ME Research UK, as well as private donations.
This project is led and managed by the CURE-ME research team at the London School of Hygiene & Tropical Medicine. Samples are processed and securely stored at the state-of-the-art University College London/Royal Free Hospital Biobank. In November 2014 the research team released a Summary Report on the Establishment Phase of the UK ME/CFS Biobank (PDF file). To learn more about the project, including how to participate and how you can help ensure the sustainability of the UK ME/CFS Biobank, please visit CURE-ME ME/CFS.
Dr Ian Lipkin has been a human whirlwind in M.E./CFS research since he became involved with the XMRV Research. He made a surprise announcement in 2013, during a public broadcast by the Centers for Disease Control and Prevention, revealing the first results from the world’s largest ever biomedical M.E./CFS study. Strong evidence had been found for immune overstimulation, both in blood plasma and in cerebrospinal fluid, and they were working hard to identify what could be causing these abnormalities. The transcript can be read in full at
If a microbiome problem can be identified, Dr Lipkin wants to establish clinical trials of treatments that could include probiotics, antibiotics followed by probiotics, restriction diets and possibly even faecal transplants. Dr Lipkin and his team will conduct the study crowdfunded for by The Microbe Discovery Project.
An imaging study by Stanford University School of Medicine (SUSM) investigators has found distinct differences between the brains of patients with Chronic Fatigue Syndrome and those of healthy people. The abnormalities identified in the study, Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome, could lead to more definitive diagnosis, and may also point to an underlying mechanism in the disease process.
The analysis yielded three noteworthy results: the CFS patients’ brains had less overall white matter (cable-like brain infrastructure devoted to carrying signals rather than processing information), aberrant structure in a portion of a white-matter tract called the right arcuate fasciculus, and thickened grey matter (the data-crunching apparatus of the brain) in the two places where the right arcuate fasciculus originates and terminates. SUSM released a Press Release in October 2014, stating that the scientists were in the planning stages of a substantially larger study.
Researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health have identified distinct immune changes in patients diagnosed with M.E. These immune signatures represent robust physical evidence that M.E. is a biological illness, and has distinct stages. "We now have evidence confirming what millions of people with this disease already know, that M.E. isn't psychological," says Dr Mady Hornig, lead author of the study, entitled Distinct plasma immune signatures in M.E./CFS are present in the course of the illness.
The researchers used immunoassay testing methods to determine the levels of 51 immune biomarkers in blood plasma samples collected from 298 M.E. patients and 348 healthy controls. They found specific patterns in patients who had the disease for three years or less, which were not present in controls or in patients who had the disease for more than three years. The research findings were published in a Press Release on Friday, 27 February 2015.
"This study delivers what has eluded us for so long: unequivocal evidence of immunological dysfunction in M.E. and diagnostic biomarkers for disease," says the paper’s senior author, Dr Ian Lipkin, who hinted about these important (but not yet published) research findings when he spoke at the UK M.E./CFS Research Collaborative in 2015. Dr Hornig adds, "Our results should accelerate the process of establishing the diagnosis after individuals first fall ill as well as discovery of new treatment strategies focusing on these early blood markers.”
I highlight research studies, along with any media coverage, in the News section on the right-hand side of your screen. You can also keep up to date via the Newsletter and M.E. Support Facebook Page. M.E. Support will be launching a research blog in due course to help unravel the science. Please Contact Me if you would like to be notified when the blog is published.
Below you will find a list of UK research projects that are looking for participants. This information is provided for your consideration, and the trials are not endorsed or supported by M.E. Support. Please select a study and follow the link to the research team’s own website.
- Invest in ME UK GUT MICROBIOTA RESEARCH: Is a leaky gut and intestinal microbes a cause for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? This IiME-funded gut microbiota foundation project at UEA/IFR is now entering the phase where patients are being recruited and the study can begin on-site. This follows a protracted R&D approval process. Now the exciting part of the study is about to begin and the team is looking to recruit patients and healthy controls. The patients are to be recruited at Epsom & St Helier University Hospitals.
- CFS-ME Registry
We are creating a community specifically for people suffering from CFS-ME (Chronic Fatigue Syndrome/Myalgic Encephalomyelitis). This debilitating disease is beginning to get more attention; it should have been eradicated decades ago. As research accelerates, large scale studies will be necessary to test theories. Positive results should lead to trials and treatment. This community is going to be the conduit to that process. As a member, you’ll be able to give a few details about your condition (illness) and see which studies are looking for participants.
International research news mailing list
- Google Scholar
This search engine helps you find relevant work across the world of scholarly research.
- Fund for Osteopathic Research into M.E.
Research into the osteopathic relief of symptoms of M.E./CFS.
- Health Rising
Dedicated to providing timely, accurate information to people with M.E./CFS and Fibromyalgia.
A crowdsourced encyclopedia of M.E. and CFS.
- M.E. Research UK
National charity that funds scientific investigation into causes and treatment.
Comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
- Science Advances
An open access journal from the American Association for the Advancement of Science (AAAS) that publishes innovative original research across all disciplines of science freely and globally.
- Science for ME
"Where Science and the ME/CFS Community Meet"
- The ME Global Chronicle
This is a free PDF magazine that gathers reports about scientific research, editorial writing, M.E. news from around the world, personal stories and creative contributions from those living with or around M.E.
- Margaret Williams
Articles on M.E./CFS by Margaret Williams and Professor Malcolm Hooper, with contributions from Eileen Marshall and others.