Trial of CT38 for ME/CFS by Cortene Inc.: big claims being made...

My summary of the results:

A small improvement on self-reported outcomes with the lower doses, no improvement or small worsening with the larger doses.

This patter is seen in all outcomes.

Sample sizes are very small.

Under serious adverse events, one occurrence of tachycardia and hypotension is listed. The authors say this was due to a dosing error.

The list of non serious adverse events suggests side effects are very common, in particular headache. There is also one event of suicidal ideation. The list suggests this drug is very stimulating.

The original plan included measurement of daily steps. These outcomes were not reported.
 
It doesn't look like there were any clinically significant changes in any of the patients in the one month interval after a single dose, if I read the data right. The sample size is too small for any meaningful statistical analysis, I think. So I guess it was really just a test to see whether the drug was tolerated.
 
Yes. However I suspect if the sample size was larger there might have been statistically significant and dose-dependent changes. Whether these reflect an effect on the illness would have been unclear. With side effects so prominent it could also be difficult to blind patients.
 
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Jaybee00 said:
Updated website I think.

https://corteneinc.com/development/
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None of those conclusions are justified given the tiny sample size and no control group.
The claims of CRHR2 upregulation do not seem to be associated with any (hitherto) published data.

The higher dosage may have resulted in slightly lower symptom scores in 2(!) participants, but one of those participants also suffered from tachycardia/hypotension, which is expected given that urocortin II (a CRHR2 agonist) is known to cause this. https://pubmed.ncbi.nlm.nih.gov/15476938/
 
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https://clinicaltrials.gov/ct2/show/results/NCT03613129

I thought there was a placebovgroup, bad memory maybe. So 14 pateints, no placebo group, a very weird primary outcome TDSS and are those massive confidence intervals in parentheses next to the outcomes?

The TDSS is a massive array of subjective outcomes mushed together. Many of outcomes may be unrelated to the underyling illness, and even it's severity. E.g. sleep problems improving 3 points improves score 3 points which could be highly indicative of biased response. Anxiety and depression account for 10 points and they likely will increase with attention/belief in treatment without intervention. You indigestion could improve, but your overall me/cfs could not.
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For all groups pretreatment baseline is 29.5, post treatment 25.3. That's about a 13% improvement, which seems similar to what you would expect with placebo group given this is an unblinded infusion.

Interestingly their is no clear evidence of dose-dependent response from lowest to highest (3.2, 7.5, 1.8, -2.9). Imo too little data and too few points to claim a peaking at the second dosage.

For secondary outcome SF-36, the group with the most improvements scored lowest at baseline, and for SF-36 both highest and second highest dosage showed negative or neutral outcomes.

The best result in the best dosage is about a 6 point improvement taking them to.... 30.7 on a SF-36 0-100 scale from 24.6. This is where the 26% improvement # comes from on cortene's update (even though its 25.1%). Putting it as a percent is kinda misleading to how large the improvement was. Going from 2 to 4 is an 100% improvement but it's also a 2 point one on a scale of 100.

edit 2: I wanted to reference these results a placebo infusion in me/cfs from RituxME. It may be expectations were higher for that drug, and I couldn't find the raw SF-36 numbers at 8 weeks, but it looks like cortene compares unfavorably to both the placebo and the failed intervention.

Overall response rates were 35.1% in the placebo group and 26.0% in the rituximab group
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So going up 6 points is a relatively minor change in the illness, again with no "no treatment group" it looks even worse.

I do get it's only a phase 1 trial but given the context, it's hard to imagine justifying optimisim in this drug. There are quite a few side-effects as well, including fatigue and most patients had a headache. It'll be interesting to see if the Bateman Horne center continues to be involved.

edit: I just saw others had looked at this, I thought it was new info my mistake.
 
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From: https://corteneinc.com/development/

1. As predicted, CRF2 appears to be upregulated in ME/CFS patients (relative to healthy human subjects).
2. Side-effects were mostly minor and resolved without intervention.
3. A short treatment (~10 hours) with CT38 resulted in symptom improvements that lasted at least 28 days (the monitoring period of the trial).
4. In the most effective dosing group, symptom improvement was:
substantial (average 26%);
effective on all monitored symptoms;
immediate (with 1-2 days of treatment);
persistent (at least 28 days); and
statistically significant (p=0.009).

5. Symptom improvement was related to total dose, suggesting that increasing the total dose could reduce symptoms further.
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1. is pure speculation as no direct measure of CRF2 expression or function was used.
2. is probably justified, but none of the other claims are justified as there was no comparison group.
3. Claims about efficacy are not justified from the data, due to to the fact that this is a pilot study (with a tiny sample size and no control group to boot!).

But more importantly, the drug, which is a peptide that has a short half life (as all peptides do), was only infused on 3 separate days. Which begs the question, what kind of treatment would be necessary to lead to the hypothesised desensitisation of CRF2 receptors? I'd suggest 4-6 weeks at least. Which leads me to believe that I we cannot assume anything about the efficacy from the data presented so far.
 
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