What’s in the pipeline? Ongoing, registered, or planned clinical trials for ME/CFS

Evelien and I were interested in what clinical trials are currently planned or ongoing for ME/CFS. It can take many years to conduct a clinical trial and report the results, so we wanted to know what we can expect to come out in the next years.

A search of databases that register clinical trials
We did a quick search of the main databases where researchers are supposed to register their clinical trials. We were mainly interested in randomized controlled trials that have the intention to test the efficacy of a treatment and less interested in phase I studies (that focus on safety testing) or open-label studies (that have no control group).

Unfortunately, the WHO International Clinical Trials Registry Platform (ITCRP) website was not functioning, due to heavy traffic generated by the COVID-19 outbreak. We did manage to search the other main databases that are the main data suppliers for the WHO, namely: Clinicaltrials.gov, ISRCTN, ANZCTR, DRKS, EudraCT, and NTR. We also had a look at the main charities that fund ME/CFS research to see if they had plans for clinical trials. The results of our search are summarized in this Google document (which should be open for all to see and comment on). If you know of any (randomized controlled) trials for ME/CFS that aren’t listed in this document, feel free to make a comment or let me know through social media.

Few drug trials, several on fecal microbiota transplantation
We found approximately 30 trials, which can be grouped into different categories. First off are drug trials, but unfortunately, there are very few of these. The one by Jarred Younger on Naltrexone is currently suspended. There is also one on Mestinon by David Systrom. That’s about it. The Open Medicine Foundation recently announced a study in Sweden that will test Kynurenine, but this hasn’t been registered yet.

Other preliminary reports such as the ones on CT38 (the drug developed by Cortene) and Cyclophosphamide (which was trialed by the Norwegian research team of Mella and Fluge) have raised hope that larger trials will follow. But thus far we couldn’t find plans, protocols, or registration of further studies to test the efficacy of these treatments.

A whole lot of shit
Secondly, there are a couple of trials into fecal microbiota transplantation (FMT) where doctors take the stool of a healthy donor and insert it into a ME/CFS patient, hoping that it will restore the gut flora and help alleviate symptoms. The comeback study in Norway will test this procedure in 80 patients, but there is also a registered Finnish study and one supported by Invest in ME at the Quadram Institute that hope to test FMT in ME/CFS.

Supplements, Chinese remedies, and behavioral interventions
There are more trials in the third category, namely those that will test supplements. The most prominent one is the one by Dikoma Shungu on N-acetylcysteine. Others plan to test a mixture of supplements that have names such as RiaGev™, ReConnect®, Gutmagnific, or ImmunoVit. In our view, many of these trials are not so much a sign of hope but an indication that the ME/CFS research community hasn’t reached the level of professionalism that patients deserve.

The same can be said about the handful of studies that hope to test ancient Chinese remedies, such as acupuncture, tao yin exercises, moxibustion, and Sijunzi decoction. It is doubtful that the investigators of these trials really know what ME/CFS entails. One trial description for example starts with the sentence: “Chronic fatigue syndrome (CFS), also known as idiopathic chronic fatigue (ICF)…” To be upfront, we have the impression that quite a few of these researchers mistake ME/CFS for unexplained tiredness of a less severe nature.

Lastly, there are trials on behavioral interventions such as the MAGENTA and FITNET-NHS studies led by Esther Crawley in the UK. Apparently, there are still a few researchers who hold high hopes of changing patients’ thoughts and behavior as a treatment for ME/CFS, despite the failures of the past. There are registered ME/CFS trials on self-paced exercise, video gaming, computerized cognitive training, relaxation methods, biofeedback therapy, and so on.

A rather bleak conclusion
We can’t avoid the conclusion that the results of our search were rather bleak and disappointing. There are few decent clinical trials for ME/CFS that provide hope that a treatment will be found anytime soon. The nature of discovery, however, is that it comes unexpectedly. We hope this overview doesn’t promote pessimistic nihilism, but that it encourages increased efforts to rapidly expand the level of funding for ME/CFS research.

Michiel and Evelien

Read our overview of registered clinical trials for ME/CFS here: https://docs.google.com/document/d/1eWt_PVdulazvqUUeBuvJP4nopTlpk9RgwzVHULoX3aI/edit?usp=sharing

 

I've also put this text on my WordPress blog, perhaps that is easier to share on social media. Here's the link: https://mecfsskeptic.wordpress.com/...stered-or-planned-clinical-trials-for-me-cfs/

 

I'm crashed at the moment so won't be double checking myself but did your search capture all that I found here? What ME/CFS research, funded by UK sources, is currently in process (as of end June 2019)?

I'd assume so but thought I'd ask anyway.

 

That's a great overview but I don't think it mentions clinical trials that hope to test the efficacy of a treatment for ME/CFS.

The process of searching for studies on databases such as clinicaltrials.gov was a bit messy because it lists a lot of provocation studies and clinical trials that are already terminated.

 

Sad state of affairs. No ideas, no clues - nothing.

 

During the Fatigatio conference today, Jonas Bergquist was asked what should be done to advance research in Europe, following the European petition. Besides a European biobank, Bergquist said that it could be useful to do lots of small pilot clinical trials like the one he plans to do on Kynurenine and that these can be seen as a method to test, probe and learn more about the underlying pathology of ME/CFS.

I thought that was an interesting perspective because people usually say that there are so few clinical trials for ME/CFS because we know so little about the underlying pathology. Perhaps clinical trials can be used to test a hypotheses about the underlying pathology.

 

Is there any reasons given as of why LDN trial is suspended?

 

Clinicaltrial.gov notice about this trial states this:

Dr Younger has been quiet as of late. Hopefully it means he is near publishing. The recent IACFSME conference had a presenter that made mention that LDN had not so much effect on fatigue, but was helpful for pain. She represented the Vancouver program and mentioned they were planning a LDN vs placebo clinical trial.

A second comment would be that COVID would slow any research down, let alone any trial. We must be extra patient in these times of uncertainty. However it is a bit jarring that there is not so much that even sounds promising. That is because we do not have scientific underpinning of the pathology yet. We must make progress in that regard in order to target the disease.

 

I've wondered about this too. I've been hoping with the COVID shut down he was using that time to finalize his publication. If he confirms his previous findings will it give ME/CFS a permanent home in neurology?

 

Great work!

Wanted to do this myself, but wasn't sure where to start

The overview makes it blatantly obvious why nothing is happening. Barely no one is researching..

 

I think that things are happening behind the scenes, but good research takes time and researchers cannot talk about it until it is published.

 

Nah ME is so underfunded, and a lot of the little research being done is nonsense. Hopefully we can get into gears a bit with the whole longcovid-scenario

 

Code:

https://twitter.com/sjmnotes/status/1315931685008048128

https://twitter.com/user/status/1315931685008048128


https://mecfsresearchreview.me/2020...stered-or-planned-clinical-trials-for-me-cfs/

 

That was my initial thought as well, but It would be interesting to have an overview of how successful treatments come about. Anyone happen to have any good reading tips on this, I'm searching for something a book like: "a history of the most successful drugs in medicine" or something like that.

Perhaps quite a lot of effective treatments are found by chance without understanding the pathology of the disease or how the drug works.

If anyone knows any (counter)-examples feel free to post it.

 

Penicillin: There was suspicion it had antibacterial properties, and Alexander Fleming put this to the test by injecting it into some of his bacterial cultures. He published his experiment in 1929 and called the antibacterial substance (the fungal extract) as penicillin.

Fleming did not convince anyone that his discovery was important. This was largely because penicillin was difficult to isolate so that drug development was unthinkable. It is speculated that had Fleming been more successful at making other scientists interested in his work, penicillin would possibly have been developed years earlier.

In 1930, Cecil George Paine, a pathologist at the Royal infirmary in Sheffield, successfully treated ophthalmia neonatorum, a gonococcal infection in infants, with penicillin (fungal extract) on November 25, 1930.

The university of Oxford made progress in making concentrated penicillin from fungal culture broth that showed both in vitro and in vivo bactericidal action

In 1941, they treated a policeman, Albert Alexander, with a severe face infection; his condition improved, but then supplies of penicillin ran out and he died. Subsequently, several other patients were treated successfully. In December 1942, survivors of the Cocoanout grove fire in Boston, were the first burn patients to be successfully treated with penicillin.

 

Then e.g. Jonathan Edwards trying Rituximab for RA. If I recall correctly he did not know much of any specific disease mechanism, other than RA being an immunological condition. (EDIT: See Jonathans reply)

My impression is that in most immunological diseases we dont know much of the specific disease mechanism, but by narrowing the immunosuppressive down and targeting specific cells, u also get closer to the disease driving mechanism.

Thi could be the case in ME, if a cyclo phase 3 study shows effect

 

Insulin:

"Before insulin was discovered in 1921, people with diabetes didn’t live for long; there wasn’t much doctors could do for them. The most effective treatment was to put patients with diabetes on very strict diets with minimal carbohydrate intake. This could buy patients a few extra years but couldn’t save them. Harsh diets (some prescribed as little as 450 calories a day!) sometimes even caused patients to die of starvation.

In 1889, two German researchers, Oskar Minkowski and Joseph von Mering, found that when the pancreas gland was removed from dogs, the animals developed symptoms of diabetes and died soon afterward. This led to the idea that the pancreas was the site where “pancreatic substances” (insulin) were produced.

Later experimenters narrowed this search to the islets of Langerhans (a fancy name for clusters of specialized cells in the pancreas). In 1910, Sir Edward Albert Sharpey-Shafer suggested only one chemical was missing from the pancreas in people with diabetes. He decided to call this chemical insulin, which comes for the Latin word insula, meaning “island.”


So what happened next? Something truly miraculous. In 1921, a young surgeon named Frederick Banting and his assistant Charles Best figured out how to remove insulin from a dog’s pancreas. Skeptical colleagues said the stuff looked like “thick brown muck,” but little did they know this would lead to life and hope for millions of people with diabetes.


With this murky concoction, Banting and Best kept another dog with severe diabetes alive for 70 days—the dog died only when there was no more extract. With this success, the researchers, along with the help of colleagues J.B. Collip and John Macleod, went a step further. A more refined and pure form of insulin was developed, this time from the pancreases of cattle.


In January 1922, Leonard Thompson, a 14-year-old boy dying from diabetes in a Toronto hospital, became the first person to receive an injection of insulin. Within 24 hours, Leonard’s dangerously high blood glucose levels dropped to near-normal levels."

So pretty random, remove X and disease X starts. Give X, and disease X stops

Maybe we can remove our autonomic nervous system and see if we feel better He he he