Open TRI-ME: Trimetazidine to treat Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A double-blind, randomised, placebo-controlled efficacy trial

[Utsikt]

Additionally, the underlying pathophysiology of this disease is yet to be fully elucidate

we will look at the current state of diabetes treatments and how these target the disease symptoms but are unable to combat the underlying causes.

I believe this logic might be flawed. How can you explain what the drugs don’t solve if you don’t know what you need to solve?

Therefore, we used a novel approach to identify molecular pathways that are not only changed in a diabetes-like state but also are reversible and can be targeted by drugs.

This makes at bit more sense. It’s the ‘look for your keys under the streetlamp’-approach, or ‘hope that the solution exists within our current means’.

 

[Utsikt]

There's a small blurb here about the work Deakin are doing on me/cfs: https://med-projects.deakin.edu.au/projects-2023.php

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yes, they write me/csf some of the time! Like many new studies it's being done by people who've wandered into this field from elsewhere; that lack of deep background doesn't increase the chance of success but nevertheless i'm always pleased to see new people coming in.

Myalgic encephaloymelitis or chronic fatigue syndrome (ME/CFS), is a chronic debilitating disease characterized by intense fatigue worsened by physical/mental activity affecting 5-6% of the population.

This does not fill me with confidence

 

[Murph]

Look, I also don't think this is the research process most likely to lead to a cure.

I do find myself attracted to a philosophical approach that seeks glimmers of light, even amid human and institutional frailty.

 

[Hutan]

There's a small blurb here about the work Deakin are doing on me/cfs: https://med-projects.deakin.edu.au/projects-2023.php

I think this looks interesting. As I understand it:

• Get blood cells from people with ME/CFS and healthy controls
• Make stem cells
• Grow the stem cells to differentiate into tissue types
• Compare the transcriptomics of the differentiated cells (ME/CFS vs HC)

If they can achieve that, then they perhaps could trial drugs on the cells. That's a long journey though.

 

[Utsikt]

I do find myself attracted to a philosophical approach that seeks glimmers of light, even amid human and institutional frailty.

I certainly don’t mind people trying different approaches.

@Hutan based on that description it seems like they might benefit from contact with OMF? I believe they’ve got a team that’s currently screening drugs on some kind of bacteria/animal models.

 

[Murph]

I think this looks interesting. As I understand it:

• Get blood cells from people with ME/CFS and healthy controls
• Make stem cells
• Grow the stem cells to differentiate into tissue types
• Compare the transcriptomics of the differentiated cells (ME/CFS vs HC)

If they can achieve that, then they perhaps could trial drugs on the cells. That's a long journey though.

I emailed Walder and he said : "No drugs yet from the me/cfs study, should be finding some later this year if all goes well".

He understands as well as we do that when a drug emerges from this process it is merely a candidate; the process increases the probability that this compound may help sufferers compared to trying drugs randomly, it doesn't guarantee a cure.

The step after that would be investigating mechanisms of action in vitro; using the drugs in any animal models that may have been developed; and after that perhaps a phase 1 trial. And if it's a low-risk generic then probably a few people trying it to see what happens.

 

[EndME]

I emailed Walder and he said : "No drugs yet from the me/cfs study, should be finding some later this year if all goes well".

He understands as well as we do that when a drug emerges from this process it is merely a candidate; the process increases the probability that this compound may help sufferers compared to trying drugs randomly, it doesn't guarantee a cure.

The step after that would be investigating mechanisms of action in vitro; using the drugs in any animal models that may have been developed; and after that perhaps a phase 1 trial. And if it's a low-risk generic then probably a few people trying it to see what happens.

I think everyone would already be extremely happy if someone could provide any reliable evidence of there being a difference in ME cells vs healthy cells since such evidence doesn't exist thus far. If I understand his ideas correctly that's also the crucial step which is required for his ideas to make any sense.

 

[Casper]

Vastarel (trimetazidine) works for me, although the effect seems to fade away after 1-2 weeks. It gives me maybe 30 % more energy, like a “back to normal” or rejuvenating feeling, without side effects or PEM. It’s not like stimulants. Subjectively, I’d compare it to Q10, which has worked in the same way for me. I don’t recall whether it worked for pain.

A former GP agreed to prescribe it to me, on my suggestion, but I don’t remember how I got the idea. Maybe I had read some old studies.

Unfortunately, later GPs wouldn’t refill it, and since it was a remedy without reimbursement, I never tried it on a long-term basis, but I can clearly say that brief courses worked well for me, from the first day.

This is just my experience, but I don’t understand the negative comments. My theory is that as long as a cause of ME isn’t known, we may assume it is caused by a variety of mechanisms, meaning a broad variety of treatments of various mechanisms should be studied. On a scale from root cause treatments to symptom masking, trimetazidine is closer to the first end of the scale.

A note: After having had the diagnoses of small fibre neuropathy and ME, I got treatment for chronic Lyme and bartonella, which helped (not least on fatigue), but that doesn’t make my experience less relevant, since I did fulfill the ME criteria, and many other ME patients may similarly have occult infections.