Reprinted with the kind permission of Cort Johnson and Health Rising.
By Cort Johnson
The Centers for Disease Control (CDC) flew in about 40 people from over two dozen organizations for the one-day CDC Roundtable on Medical Education and ME/CFS. It was a busy 24 hours. Everyone flew in the night before to a hotel near the airport, spent the next day working at the hotel, and then flew out that night.
Dr. Klimas, Dr Bateman, Dr. Montoya, Todd Davenport, and Lily Chu were among the medical professionals attending. Sadie Whittaker represented the SMCI. Vicky Whittemore was there from the NIH. Mary Dimmock, Ken Friedman, Terri Wilder, Charmian Proskauer and Wilhelmina Jenkins represented various advocacy organizations.
It was particularly good to see WebMD and Medscape – which was shooting an ME/CFS education video the next day with Dr. Klimas, Dr. Bateman and others – at the meeting as well as a few professional organizations (American Academy of Family Physicians, American Academy of Pediatrics, American Nurses Association, Georgia Chapter of The American Academy of Pediatrics, Kansas Department of Health and Environment). Many more professional organizations could have been represented – Dr. Unger said they were invited – but they declined.
The Roundtable was part of a continuing outreach effort by the CDC to bring in stakeholders in ME/CFS (doctors, health care professionals and patients) to improve how they communicate about chronic fatigue syndrome (ME/CFS) to the public. Two years ago a similar group met.
The CDC was looking for input on draft materials on how to educate physicians about ME/CFS and how to help prepare ME/CFS patients to meet with physicians and get their story heard.
I was lucky enough to sit at a table with Dr. Klimas, Todd Davenport of Workwell, Vicky Whittemore of the NIH, a CDC rep (who constantly critiqued her organization’s materials :)) and a CDC facilitator.
Everything was on the table – content, formatting – whatever could improve the delivery of the materials was fair game. If it was input they wanted, they definitely got it. The suggestions came fast and heavy. It was rare to go for a couple of paragraphs without a suggested change. The CDC seemed amenable to changes: the time the meeting was done our facilitator had made pages and pages of notes.
At the meeting I got a chance to talk to Dr. Unger about the CDC’s multisite study and Dr. Klimas about her upcoming ME/CFS clinical trial.
The CDC Multisite Study
The huge multisite study featuring seven different ME/CFS doctors and their patients began in 2012. Dr. Unger gave a presentation on the initial findings at the FDA Workshop in 2013. In 2014 she reported analyses on the data were underway, that publishing was a priority, and that papers on medication use, medical history would be submitted as soon as possible. Four years later, except for a summary of the study’s makeup in 2017, nothing has been published or reported since.
The study was truly massive: 471 patients in the first round and even more in the second round which added two rarely studied subsets (pediatric patients and the severely ill) and two comparison groups (healthy controls and an ill comparison group including people with fibromyalgia, rheumatoid arthritis, multiple sclerosis, and cardiovascular disease). The practitioners agreed to standardized testing protocol. They still do their own tests, but all patients in the study got a core set of tests.
Some biologic data (routine laboratory and morning cortisol) was collected and an exercise study was reportedly to be done. The blood and saliva samples will go to form the basis of a potentially very helpful biorepository, given the extensive data collected from these patients.
Virtually everything the CDC could learn about these patients they have learned: symptoms, illness trigger, medical history, family history, medication use (supplements to drugs), lab test results, and functional level. The study should improve diagnostic protocols and help clarify patient subsets. The functionality and medication use data should allow the CDC to provide data on the effectiveness of treatments (IVIG, Ampligen, antivirals, etc.) rarely used by most doctors. The study should also be able to tell us if spending a lot of money on more proactive treatment protocols is more effective than going with more conservative treatment protocols.
Importantly Dr. Unger has said the results will help inform the CDC’s future educational materials. The study, then, could help surmount the “evidence-based” result hurdle which, for years, kept the CDC tied to the only protocols (CBT/GET) which have received much study.
The CDC appears to have decided not to report on the first round of the study and will combine the results of the first and the second round – which has just finished up.
The CDC’s funding woes have not helped. For the past couple of years the CDC’s funding has been cut out of the Congressional Appropriations Bill and then put back in. Unger said she has to rely on budgetary maneuvers (which take time out of her day) to keep the work flowing, plus not having a set budget every year does not help with hiring personnel.
More on the Multisite Study:
Other CDC Activities
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The CDC gets a lot of flack, but they’re involved in a number of potentially very helpful activities including:
- The preparation of an educational curriculum on ME/CFS for medical students that will hopefully help to finally introduce medical students to this disease.
- Providing funding to the National Association of School Nurses to create the first-ever surveillance system of ME/CFS among US school children and education of school nurses about the disease.
- Creating an algorithm to identify people with ME/CFS using electronic records in a managed care setting – hopefully helping doctors identify previously undiagnosed cases of ME/CFS.
- Reviewing the published literature and working on ways to capture the treatment protocols of ME/CFS experts in such a way that they can provide the basis for treatment by other doctors. This appears to be an attempt to bypass a missing gap in ME/CFS treatment – the few clinical trials, which has weighed heavily on the CDC’s need for “evidence-based” results. The CDC’s ability to validate or provide a strong basis for some of the treatments used in ME/CFS would be a major step forward for patients.
- Integrating ME/CFS into an optional module in the 2019 Behavioral Risk Factor Surveillance Survey (BRFSS). The BRFSS – the largest survey of its kind – will allow states (which opt in) to collect ME/CFS data on illness burden. States which opt in will surely get a surprise when the figures for ME/CFS patients blow away most other diseases. We vitally need more burden of illness data to advocate for ME/CFS.
- Working with the FDA to provide acceptable clinical outcome measurements that drug companies can use to assess the effectiveness of their treatments.
- Co-funded with the NIH the ME/CFS Common Data Elements Project.
System Reset – Dr. Klimas’ ME/CFS Clinical Trial Set to Begin
It’s always fun to sit at a table with Dr. Klimas. The information just flows and flows as her nimble mind considers one topic after another. It’s like a force of nature – it’s fun to just to sit back and watch her work.
Cortene’s attempt to do a system reset in ME/CFS has generated a lot of interest. Cortene brought a new drug to the field, funded it, and enrolled ME/CFS doctors in the CT38 trial that is now underway. Dr. Klimas got her ME/CFS reset trial going using another technique – coercion. Both clinical trials are unusual in that both hope to reset ME/CFS patients systems back to normal – forever.
When you can’t get funding through normal channels, you get creative, and Dr. Klimas has been nothing but creative in her ability to build a Gulf War Illness (GWI) modeling platform, hook ME/CFS into it, and use her GWI funding to explore ME/CFS. Her group has grown and grown and now includes computational biology, animal modeling, genomics, cell biology specialists and more.
Now she’s using another disease – Parkinson’s disease, no less – to get a treatment trial for ME/CFS underway. Parkinson’s Disease may not be so far off the beaten path as one might think. When Dr. Klimas opened the Institute of Neuroimmune Medicine in 2013 she included it, along with M.S. and other neuroinflammatory and neurodegenerative diseases, within the Institute’s purview.
That may have been prescient indeed. It turns out that Dr. Klimas’ engineering-computational biology techniques are in demand. She went way out on the skinny branches when she poured a ton of resources into an unproven and innovative approach to disease. When I asked Gordon Broderick, the head of the program at the time, if anyone else was doing what they were doing, the answer was an emphatic “no”.
Dr. Klimas’ team has gathered an amazing amount of data on what happens during and after ME/CFS patients’ Achilles heel – exercise. Measuring ME/CFS patients at nine time points before, during and after exercise, she’s gathered data on gene expression, cytokines, flow cytometry, cell function, neuropeptides (9 million data points total) in ME/CFS and GWI.
The models found that exercise first kicked off a mess of inflammatory pathways in ME/CFS which then faded in importance. Four hours later oxidative stress, the autonomic nervous system, stress and sensory pathways, and HPA axis pathways became upregulated. The models indicated that if you could tamp down inflammation and then try to reset the HPA axis, the system might revert to normal.
At least one major disease group thinks Dr. Klimas has struck gold with her approach. The Parkinson’s Foundation is apparently so excited at the possibilities of computational biology that they wanted to transport her and her entire team into Parkinson’s research. When that thankfully failed, they gave her a nice, big budget to get access to the computational modeling platform and train another team how to use it.
(The Parkinson’s effort will use the Institute’s modeling platform to understand the dynamics of the central nervous system in producing the disease. Studies are already underway using mouse models (Parkinson’s has a couple of them) to improve the current model.)
In return, she asked the Foundation to fund a 20-person ME/CFS trial. That trial is expected to begin this fall. It will include post-menopausal women and use the same drug combination (etanercept and mifepristone) used in the GWI trial.
Mouse models in GWI indicated that using the drugs in a staggered protocol – first to tamp down inflammation and then to reset the HPA axis – caused the immune, autonomic, hormonal, etc. systems of the mouse to normalize. Klimas does not have an animal model for ME/CFS, but the computational biology modeling has for years suggested the same will happen in ME/CFS. She just hasn’t had the funding to test it until now.
The participants will do an exercise test – then take down inflammation using etanercept for a month and then rebalance the hormonal system using mifepristone. If the model is correct, the treatment combination will push ME/CFS patients’ systems back to health.
The Gulf War Illness trial started earlier this year. I don’t know the results. The ME/CFS trial should either have started by now or be beginning shortly. (It’s already filled up.)
Check out Dr. Klimas’ fascinating approach to ME/CFS in a Solve ME/CFS Initiative Discovery Forum Talk
Speaking of the post-menopausal women in the study, I asked Dr. Klimas if menopause tended to hit women with ME/CFS harder than usual. She noted that a CDC study found that menopause tends to hit women with ME/CFS eight years earlier than normal. In her experience, women with ME/CFS do better staying on bioidentical hormones (estrogen/progesterone). She found that out after taking some women with ME/CFS off of bioidentical hormones when an estrogen study found an increased risk of cancer. Taking women with ME/CFS off of the bioidenticals sometimes caused massive and hard to recover from crashes.
We’re in for some exciting results – from the long awaited multisite study, to the Cortene trial, to the metabolic trap hypothesis work (next blog), and to Dr. Klimas’ two-drug trial. No one has ever had the audacity to suggest they might not only help people with ME/CFS but may be actually able to reverse it. Now two groups think that’s a possibility and, if the metabolic trap hypothesis works out, we’ll probably be able to add a third group to that set.
It may be that none of these efforts will work out but each should still inform us about ME/CFS. Dr. Klimas, for instance, will be gathering massive amounts of information in her trials and has powerful models she can tweak if that particular drug combo doesn’t work out. Similarly, Ron Davis has the resources of the Stanford Genome Technology Center, a huge study underway at Bruce Snyder’s lab and a new ME/CFS Research Center at Harvard if the metabolic trap doesn’t work out.
Meanwhile the CDC’s multisite study – perhaps the biggest study ever done in ME/CFS – might be able to start getting ME/CFS experts protocols into the medical mainstream giving patients more options. Plus the CDC is working on ways to increase diagnosis rates, get ME/CFS into medical school curriculum’s, produce acceptable clinical outcome measures for drug trials and more.
About the Author: Cort Johnson has had ME/CFS for over 30 years. The founder of Phoenix Rising and Health Rising, Cort has contributed hundreds of blogs on myalgic encephalomyelitis, chronic fatigue syndrome, fibromyalgia and their allied disorders over the past 10 years. Find more of Cort’s and other bloggers’ work at Health Rising.