A Novel Nutriceutical Treatment of ME/CFS, 2017, Comhaire

'stepwife elimination'? Sounds like a family matter.

 

sorry... should read stepwise elimination.

 

@ME/CFS Would you mind letting us know the patent number?

 

The formulation is fully protected during 12 months while the "novelty" is being checked. During that period "provisional protection" completely covers the intellectual property-rights of the inventor. The complementary ingredients of the nutriceutical are: Vitamin B1, alfa-lipoic acid, acetyl-l-carnitine, and ubiquinone Q10, which all act in synergy with the sodium dichloroacetate. Thanks to this synergy the dose of sodium dichloroacetate can be reduced to far below the level of potential toxicity. By inhibiting the pyruvate dehydrogenase kinase, sodium dichloroacetate has been proven to activate the Kreb's cycle of aerobic metabolism, since the enzymatic activity of pyruvate dehydrogenase is increased. This enhances the production of ATP, the carrier-molecule of cellular energy. Once again, I wish to underscore that many so-called "cases of ME/CFS" are not primarilly due to an enzymatic problem causing poor mitochondrial function, but are "cases of secundary syndromes of fatigue" caused by another disease (as exemplified in my previous paper, and detected by me in ever more patients). Finally, please take into consideration that English is not my "mother-tongue", which explains liguistic errors.

 

Thank you for your reply. It was partly the dose level of the sodium dichloroacetate I was wondering about, given the potential for toxicity.

 

A pragmatic trial is, by definition, not blinded, since it is an open-label, prospective, real life trial. Please look up the definition of "pragmatic trial" via internet.

 

The dose level is between 5 and 10 mg per kg body weight, generally 400 mg once per day.

 

I looked up pragmatic trials and found a good review in NEJM. It says:

It is only after phase 3 drug trials that we have any real understanding of whether the treatment is beneficial, who might benefit most, the potential adverse effects, and the most cost-effective implementation. The ideal time to perform a pragmatic trial would be during the implementation stage of a complex intervention or the postmarketing phase of drug evaluation, to help provide an understanding of what the effect of introducing the new technology might be on overall public health.

That does not seem to have much to do with early proof of concept studies. Also it says:

In many situations, the need to avoid reporting bias will override purist pragmatic considerations, making blinding the optimal approach. In complex intervention trials, in which blinding the intervention is often impossible, it is usually possible to blind the assessment of outcomes.36 In any trial, the advantages and disadvantages of blinding must be considered; blinding is particularly important when the reporting of key end points or safety events could be biased in an open trial.

 

Is this only in regards to a fatigue questionnaire again?

Will you be conducting a more probative trial in the future, with controls, blinding, and objective outcome measurements? A successful treatment for ME/CFS would be groundbreaking, and the extra expense and hassle of such a trial would certainly be worthwhile.

 

A pilot, open label, proof-of-principle, pragmatic trial is the first step in a sequence of validation. For the patients who benefit from the treatment, the effect is what counts. In my view of medicine (which I practice since 54 years), the feeling of health and happiness of the patients is what is of pivotal importance.
In addition, there is a remarkable fact namely that the probability can be predicted that a particular patient will or will not benefit from treatment. This prediction is based on a mathematical formula that is derived from the result of the regression analysis with stepwise elimination (area under the ROCcurve= 0.91).

 

Could you clarify if you will be going on to a second step of validation, with objective outcomes, a control group, and blinding? The effect does indeed count, but we need better trial design to know if there actually is an effect or not.

 

I am not sure I really agree with that, having been heavily involved in devising and executing trials at all stages. My understanding from NEJM is that the term pragmatic was invented to deal with late stage assessment of practical implications in a real clinical setting after pilot and proof of concept trials had been done to establish efficacy. And pilot trials are more or less by definition not proof of concept trials because 'pilot' means preliminary, implying preliminary to a formal demonstration of efficacy, which is what a proof of concept trial does.

My impression is that you are as far as a pilot open study. That is fine in terms of establishing tolerability and feasibility of doing a full study of efficacy but it does not allow conclusions about efficacy to be drawn.

 

As argued before, this is an open-label, proof of principle or proof of concept pilot trial performed in real life circumstances and, therefore, it may be called pragmatic. The message that I have transmitted is that a foodsupplement, that inhibits Pyruvatedehydrogenase kinase and that stimulates energy production by the Kreb's cycle does, indeed, siginificantly improve the health situation of some patients suffering from long-lasting so-called refractory ME/CVS. I am aware of the fact that additional studies are necessary, and I have quite some experience in the field of clinical research.

 

Reply
this is indeed based on a relatively small number of observations, and is performed a posteriori, by calculating the formula derived from the logistic regression analysis (MedCalc statistical program).

 

What about trial of Ibrutinib
There’s a video on youtube,targeting B cell receptor signalling for anti cancer therapy. It hits on a lot of keywords for me pkc being one
If I develop one of these types of cancer treatment may cure both as per fluge mella I think that’s the only way I would receive something like this
It’s like a static pre cancer

 

@ME/CFS

Dear Dr. Comhaire (hoping you are still here),

Are you still tracking the patients in your DCA trials? Are they still repsonding to the treatment or is there any indication of tachyphylaxis?

Thank you.

 

Using what biomarker/predictors?

Claiming you have a strong predictive method, without actually stating the method itself is well, unconvincing.

 

Fatigue with PEM has certainly been the main expression of my illness over the past 34 years.

And the PEM "crashes" mainly involve profound exhaustion.

I don't associate with the "fatigue isn't a problem" proclamations up-thread.

I do care about "fatigue". Very (very) much. In fact, fatigue and brain-fog have the biggest impacts on my quality of life.

For me, it is the #1 top symptom (by far).

Bill