r/longevity • u/Das_Haggis • 2d ago

Synaptica's neuromodulation system reduced Alzheimer’s disease progression by 44% in Phase 2 clinical trial. Company planning a pivotal Phase 3 trial, slated for later this year.

https://longevity.technology/news/neuromodulation-system-reduces-alzheimers-disease-progression-by-44/
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u/neuro__crit 2d ago edited 2d ago
  • Underpowered study; only 32 completed the 52-week study, but their calculated power was based on effect sizes from the 2-week pilot; their minimum number was supposed to be n=48.
  • On the primary outcome (CDR-SB), the confidence intervals overlap: rTMS [0.68, 2.04] vs sham [1.85, 3.05]. This makes the effect size seem modest, and not dramatically different between groups. And notice that the time × group interaction (buried in the paper near fig 2) was p = 0.038, it's barely significant.
  • Attrition might be non-random (especially if there was inadequate blinding); also issues with baseline variability because this was actually an extension of a previous 24-week trial, with 17 new participants enrolled.
  • Secondary outcomes; MMSE, NPI, and FAB were borderline significant or nonsignificant. A weird result if this really "reduced Alzheimer's progression by 44%."
  • Are they correcting for multiple comparisons? Unless I'm missing it, I don't see anything in the paper about that. For all we know, this could just be p-hacking.
  • Does rTMS even work? They say that "rTMS works by restoring DMN connectivity and cortical plasticity" but then the neurophysiology endpoints they used were negative except for change in baseline DMN connectivity, which could easily be spurious in such a small sample.

TLDR: Another junk study.

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u/Defiant-Lettuce-9156 2d ago

How many resources are used for these “junk” studies?

Do the people who fund these studies even care?

I just can’t believe that there are so so many studies out there that are almost useless because sample sizes are too small, etc… And worse yet some of these studies cause a lot of misinformation to spread. What is the point?

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u/Billiusboikus 1d ago edited 1d ago

It's a phase 2 trial. Phase 2 trials have to be small. You don't want to unleash a drug on thousands of people that may not be completely safe if you don't even know it's remotely effective. 

Look at statins. Many health services think we should all take statins, even if the benefits are fairly minor and only manifest across whole populations.

Further, any drug wont be the final form. Many cheaper more effective derivatives are found. This is simply how medicine works.

Study hyping is unfortunate but just the way things work when you have to pull funding 

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u/Defiant-Lettuce-9156 1d ago

Thanks for your reply that does make sense