We're here to provide a place for honest discussion of research including critiques such as yours. If a project is badly designed, of course you can say so with reasons, as you have done.
News From Jarred Younger / Neuroinflammation, Pain, and Fatigue Laboratory at UAB, From Aug 2020
- Thread starter wigglethemouse
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Utsikt
Senior Member (Voting Rights)
This is one of the least harsh comments I’ve read today. The trial design you describe is seriously flawed, to the point that it’s difficult to not suspect bad faith attempts at getting a seemingly positive result to use as an argument for continuing the prescription of LDN.
Nacul’s trial had 40 % responders in the placebo group..
ChronicallyOverIt
Senior Member (Voting Rights)
In the video he wouldn’t go over the trial design, is it on clinical trials.gov? If so I’d be interested in looking at it. A clinical trial without placebo is basically useless and huge waste of money. He should heed Dr. Nacul warning on his clinical trial of LDN, observational alone is largely useless. So odd he would choose to do that when he has hundreds of videos dissecting trials and research. He was critical on the rapamycin trials for that very reason! Rose colored glasses?
Yes, previously posted here.
https://clinicaltrials.gov/study/NCT07285473
The participants will be masked to what dose they get, but there's no control group getting no LDN. So it could still show if higher doses give a stronger effect. I'm not sure why it says single-blind. Will the clinicians and researchers know the doses during the trial?
Jonathan Edwards
Senior Member (Voting Rights)
A dose ranging study like this is OK as long as it is powered to show differences between doses and only the differences between dose groups are taken as indicative of effect. Often there would be a zero dose group but not necessarily. Single blind here means that the patients are blinded. Since the medication is mailed there may be no problem with the investigator knowing who got what dose, although one would want to be sure that assessments were blinded.
Jonathan Edwards
Senior Member (Voting Rights)
From what I can see on the net a typical dose for LDN would be 3 -4.5mg. The lowest dose in the study is 1.5mg. I think a wider range would be sensible. In a dose ranging study you normally assume that your lowest doses are sub-therapeutic, or at least well below optimal.
neophyte32
Senior Member (Voting Rights)
But seriously, what is the point of this study? To fund his lab?
It’s just so annoying and baffling for laypeople like me. Isn't there anything better to do? He’s obsessed with neuro-inflammation so let him prove it once and for all, instead of doing a 50th study on LDN (a poorly designed one, at that).
It’s just so annoying and baffling for laypeople like me. Isn't there anything better to do? He’s obsessed with neuro-inflammation so let him prove it once and for all, instead of doing a 50th study on LDN (a poorly designed one, at that).
Utsikt
Senior Member (Voting Rights)
Some people are doing 0.1 mg or even lower and claim that they notice an effect (both positive and negative).
I think it would have been interesting to see a trial where you do patient-decided titration, but with multiple arms.
If you don’t want to do placebo for recruitment purposes, you could do one arm with 0.1 mg regardless of what the patient choses, one arm with intervals of 0.1, 1.5, 3.0, and 4.5, and one with 1.5, 3.0, and 4.5.
The patient can chose to stay or go up, or go down to the previous dose (but have to stay there if they go down).
In terms of blinding: would it be ethically appropriate to not tell them beforehand that one arm would not go up?
The video is about measuring ATP in the brain (he wants to check if less ATP is being produced by mitochondria in pwME and related conditions). Says this hasn't been possible to do until now because we haven't had a way to measure the phosphate in ATP.
He reports that a new device, a phosphorus head coil (31P head coil), has been built to do this. I gather from the way he's talking about it that it would work much like an MRI, with the MRI target molecule hydrogen replaced by phosphate. Apparently one of these head coils is being built for his lab and he expects to receive it in Oct of this year. He's going to work on getting a grant to fund a study comparing pwME to healthy controls.
He references this preprint: Reduced ATP-to-phosphocreatine ratios in neuropsychiatric post-COVID condition: Evidence from 31P magnetic resonance spectroscopy, 2025, Schilling+ which he says (I haven't checked) found low ATP in the mid-cingulate cortex of pwLC and neuropsychiatric symptoms. He says "this region is critical for combining cognitive and emotion signals that drive effort and persistence" and that the mid-cingulate not working properly would make it almost impossible to do anything. Haven't looked into that claim either, but always happy to hear about a new part of my brain that could be misbehaving...
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Oh, he is promoting the Renegade Research trial of photobiomodulation device, funded by Solve ME. The one with the head harness and an infra-red light. (and also the vagus nerve stimulator)
Jarred Younger is in full-on hype mode:
I think we probably need to look at the evidence base for all of those claims, because so many people with great influence in the ME/CFS community are lining up to throw their authority behind the idea.
Younger talks about the 'great design choices' of the study. Specifically the testing of two treatments at one time:
Solve ME is doing a talk on the study on November 6, when they will share the protocol. Perhaps there will be some sham treatments, although SolveME didn't seem to be saying that there will be yesterday. Perhaps there is still time to lobby Renegade Research, SolveME.
Younger is involved, from memory Todd Davenport is too, we've talked about this elsewhere. So, that is more people to lobby.
Jarred Younger is in full-on hype mode:
I think we probably need to look at the evidence base for all of those claims, because so many people with great influence in the ME/CFS community are lining up to throw their authority behind the idea.
Younger talks about the 'great design choices' of the study. Specifically the testing of two treatments at one time:
There is no mention there of the possibility that a treatment doesn't work, or that neither treatment works.... Or that the trial design is so hopeless that actually there is no chance of null results. There is no criticism of this study at all.
Solve ME is doing a talk on the study on November 6, when they will share the protocol. Perhaps there will be some sham treatments, although SolveME didn't seem to be saying that there will be yesterday. Perhaps there is still time to lobby Renegade Research, SolveME.
Younger is involved, from memory Todd Davenport is too, we've talked about this elsewhere. So, that is more people to lobby.
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Felis Catus
Senior Member (Voting Rights)
Maybe I'm dumb and ill-informed but I cringe when I see trials for those head devices. Can't help but wonder if they're a modern tech version of magnetic bracelets or whatever people used to wear for healing.
Has he never not been?
SugarSquared
Senior Member (Voting Rights)
I think this is the perfect example of what you're talking about on the SolveME thread. Funding poor quality research and poorly evidenced treatments is not a neutral thing. I wish the same hype was put into more evidence-based research. Maybe we'd get somewhere faster.
It’s really annoying. I don’t know if the study’s been badly designed or what, but if this stuff is so powerful, and if they actually believed in it, they’d take precautions. (I reckon they’ve tested it on a very small scale and found it had no adverse effects.) Or perhaps we know now that it doesn’t affect animals (there are adverts for it at every vet’s).... I reckon it has absolutely no effect at all.
But whatever the case, it’s not sensible to rush headlong into unproven theories using equipment that’s barely been tested.
But whatever the case, it’s not sensible to rush headlong into unproven theories using equipment that’s barely been tested.
SWA
Established Member
No specific tests, no biomarkers, and no established treatment—so what can be done beyond further research?
I would suggest that the search for answers should not overlook possible underlying or pre-existing conditions, whether already known or yet to be identified. A thorough review of a patient’s complete medical history could reveal important patterns, associations, or contributing factors that might otherwise be missed.
My own lifelong medical condition has involved extensive laboratory testing, MRIs, CT scans, X-rays, and genetic investigations. It has led to numerous surgeries, ample medication, different therapies, and countless recommendations for over-the-counter supplements and homeopathic approaches—yet no effective treatment.
In the end, nothing has truly worked, perhaps because the actual culprit has never been identified. That raises an important question: why? Is science looking in the wrong places? Or are potentially significant clues already present in what is known—within a patient's history, previous findings, or established medical knowledge—but not being revisited or connected in new ways?
In my own case, medical professionals have also been unable to explain why my IgM levels remain persistently elevated. This is precisely the kind of unresolved finding that raises the question of whether an important clue is already present but has not yet been fully understood or connected to the broader clinical picture.
I would suggest that the search for answers should not overlook possible underlying or pre-existing conditions, whether already known or yet to be identified. A thorough review of a patient’s complete medical history could reveal important patterns, associations, or contributing factors that might otherwise be missed.
My own lifelong medical condition has involved extensive laboratory testing, MRIs, CT scans, X-rays, and genetic investigations. It has led to numerous surgeries, ample medication, different therapies, and countless recommendations for over-the-counter supplements and homeopathic approaches—yet no effective treatment.
In the end, nothing has truly worked, perhaps because the actual culprit has never been identified. That raises an important question: why? Is science looking in the wrong places? Or are potentially significant clues already present in what is known—within a patient's history, previous findings, or established medical knowledge—but not being revisited or connected in new ways?
In my own case, medical professionals have also been unable to explain why my IgM levels remain persistently elevated. This is precisely the kind of unresolved finding that raises the question of whether an important clue is already present but has not yet been fully understood or connected to the broader clinical picture.