The LIFT trial (OMF) - Pyridostigmine (mestinon) and Low Dose Naltrexone (LDN)

While I'm not excited about these drugs perse. My response wasn't great; mestinon some improvements but minor and LDN side effects galore and messed up my sleep for a long time. Actually I am not sure it ever recovered, but it could give us some more answers. However the hyping is what gets to me. I thought it was rather painful although unfortunately it's something we've come to expect from OMF. Not sure which one is worse.

 

https://me-pedia.org/wiki/Mestinon

Gulf War Illness
Pyridostigmine was given to Gulf War personnel to protect them from nerve gas.[17][18] Dr Robert Haley reportedly found that pyridostigmine is involved in two of the three syndromes of Gulf War Illness. He reported that the nerve gasSarin|sarin]] interacted with pyridostigmine; the pesticide DEET did the same. These interactions (as well as drug alone) caused brain damage to 175,000 US Gulf War personnel.[19][20][21][22] Gulf War Illness, possible interactions with DEET, other pesticides or organic solvents are not mentioned in the patient information.

 

I have mixed feelings. One the one hand, it could address the use of off-label drugs that we've been throwing around for decades. On the other, what does it say about progress in general that OMF is trialing drugs that have been around and unconvinced for decades? That they have to look backwards to LDN after all the millions in support.

And these trials have been floated around for years anyway, so it's not like this is being done at lightning speed. Systrom has been talking about Mestinon for years. Fwiw, the drug did nothing for me, maybe a mildly stimulant.

I don't think any information found out in these trials will move research or our understanding of the condition forward. I'm skeptical they will have major impacts that lead to being more available to patients with non-specialists. Even if they show the drugs are ineffective, others will pop up off label to take their place.

 

We haven’t met @Perrier but I haven’t tried it for the simple reason that my doctor won’t prescribe it to me as it is off-label. Regardless, while people may have reported some improvements, I question whether it falls into the placebo effect and the improvements are acceptable in approving this as a ‘treatment’. I have not heard people moving up in functionality scale or returning to work and/or normal activities. We also are being told that the improvement will take several months which always raise a red flag because people are likely to improve on their own as part of normal fluctuation of the disease.

The heartbreaking thought about this trial is that we won’t get a result publication for at least 2 years. and this is ‘just’ LDN (and Mestinon).

 

LDN doesn't work based on numerous anecdotal reports, as pointed out by @Perrier. This is a UK-heavy forum where (useless) treatments are generally not available due to socialised medicine. For those of us in other countries who have tried all sorts of meds including LDN, this is a big disappointment, although entirely predictable based on past OMF behaviour. And we already have a trial showing that Mestinon doesn't do anything.

For what it's worth, LDN gave me serious insomnia and worsened my gastroparesis. I wouldn't recommend this treatment.

 

They mentioned that this trial would help them build experience for future trials, and I am not against that. There is a big need for capacity building in clinical trial and while this is a softer target, they will be looking at objective measures which is a good thing.

Building capacity for clinical trial, establishing protocol, FDA approval, funding for it, ethics approval for drugs, multi-Center clinical trials, evaluating and reporting adverse events, interpreting the data, you need to get that kind of experience somewhere. Our very few experts may or may not have it. Most have some experience in simple research, typically small cohort.

 

Jarod Younger (brain 'on fire' guy) did a small study in 2014 and found that LDN helps with pain syndromes.

 

That's a really valid point, but I'm a bit worried about the ethics of getting the experience this way. These drugs aren't benign and there's little to suggest they work for substantial numbers of people, and whilst I can see the arguments that it'd be useful to put LDN to bed once and for all, I'm still uncomfortable.

 

I'm another for whom LDN destroyed sleep and it's proving difficult to get reestablished.
Despite GPs being reluctant to prescribe off label, it isn't difficult to get hold of in UK via a pharmacy with a doctor who will prescribe following a phone consultation.
It will be interesting to see if a clinical trial supports usefulness but I'm not hopeful. Both my attempts produced problems.

 

I have a few friends in the UK & Ireland who are on LDN, but it has not really helped, according to their reports. Folks are desperate and are willing to try almost anything. No substance so far touches the core problem of Exertion Intolerance. If trialling these 2 drugs is a way of learning how to do trials, doesn't this means decades of this sort of stuff which does not move things forward. Or does this reveal that they don't have any solutions for this illness? The reports for the results of these 2 trials will likely by 2+ years (though why they didn't present a timeline is beyond me). This whole episode has been very unsettling and really worrisome.

 

I'd say it probably indicates that there isn't anything else to try.

But what's behind my unease is that it's not getting funding and running trials that's the difficult bit. They could buy in that expertise, there must be thousands of researchers in the US who've made that journey with other treatments, other illnesses.

The difficult part is establishing where your cohort is starting from in terms of their ME and level of function, and then working out how to measure it again at the end so that you can say whether there was an effect. What do you measure, when, how often, how long do you follow up? Those are the unique challenges with ME. And you don't need to be trialling a drug to work that out; you need really in-depth work with patients.

 

I wonder if the results will be based on questionnaires. I hope they use fitness counters or maybe iCPETs.

 

The reason some patients think LDN is effective is because it can help with neuroinflammation, which can have similar symptoms to ME.

It's like if you took probiotics for GI symptoms, they don't treat ME but if you have GI symptoms as a result of ME they may help a bit.

I can't see any useful information coming out of this study. At best we can expect a minor improvement in a small subset, and then we will have the usual debate where one side says "no it doesn't work" and the other "yes it works look and this is proof ME is neuroinflammation".

How about we do some real science instead?

 

I can see this happening. I do wonder if the negative findings from this study are even all that useful. With Rituximab, you have some pretty definite answers about b-cells (but I guess not all types). With LDN? Is it really the definitive anti-neuroinflammation drug? Is there definite neuroinflammation in me/cfs? Will LDN put that to rest?

 

https://twitter.com/user/status/1721920539327934628



https://www.omf.ngo/treatment-trials/

 

Amazingly, all that machine learning and all those Network Medicine models came up with LDN and Mestinon, which were surely invisible to conventional analysis.

It would really be nice is OMF communications weren't so obviously fake.

 

Anyone remember this one? LDN/Trazodone.


Low Dose Naltrexone Drug Combination Proposed for Chronic Fatigue Syndrome (ME/CFS)

https://www.healthrising.org/blog/2016/02/04/low-dose-naltrexone-combo-chronic-fatigue/