New clinical trial for Mestinon

[Murph]

https://clinicaltrials.gov/ct2/show/NCT03674541?cond=ME/CFS

 

[Mel9]

https://clinicaltrials.gov/ct2/show/NCT03674541?cond=ME/CFS

Interesting!

 

[voner]

very interesting, I have always wondered about the physiological dynamics of Mestinon when it works . here is a quote from the trial description that describes Dr Systroms thinking (my bolding of the text):

Detailed Description:
The hypothesis of the investigators' study is that small fiber polyneuropathy is a cause of low biventricular filling pressures/preload failure of the heart and poor oxygen extraction in the muscle bed, leading to symptoms of exertional intolerance and post-exertional malaise. The objective of this study is to examine the exercise response to pharmacologic cholinergic stimulation in patients already undergoing a clinically indicated level 3 cardiopulmonary exercise test (CPET). This will be achieved by inhibiting acetylcholinesterase with pyridostigmine, thus increasing acetylcholine levels, downstream levels of norepinephrine, and enhanced vascular regulation.
To test our hypothesis, the investigators propose the following specific aims:

1. Define the gas exchange responses, such as oxygen uptake, end-tidal carbon dioxide (CO2), and ventilatory efficiency to pyridostigmine
2. Define the hemodynamic responses, such as right atrial pressures, pulmonary capillary wedge pressures and cardiac output to pyridostigmine
3. Evaluate skeletal muscle oxygen extraction to pyridostigmine

These determinations will occur during a clinically indicated level 3 CPET, which includes exercising on a stationary bicycle with a right heart catheter (RHC) and a radial arterial line in place. To stimulate the cholinergic response, a single dose of an oral acetylcholinesterase inhibitor, pyridostigmine, versus placebo will be given after the level 3 CPET. Recovery cycling will be performed after a rest period of 50 minutes. This will be administered in a double-blind, randomized control trial.

 

[Mary]

@Murph - I'm so glad to see this! Someone asked me the other day if I had thought about trying mestinon, which I hadn't, really.

Do you know what type of doctor would prescribe this? e.g., an endo, cardiologist, GP, etc? I'm guessing it's probably whoever is willing to listen to one of us!

 

[kangaSue]

@Murph - I'm so glad to see this! Someone asked me the other day if I had thought about trying mestinon, which I hadn't, really.

Do you know what type of doctor would prescribe this? e.g., an endo, cardiologist, GP, etc? I'm guessing it's probably whoever is willing to listen to one of us!

Gastroenterologists can prescribe Mestinon too as it can also be an effective GI motility agent when acetylcholine signalling might be impaired, such as with Autonomic Neuropathy.

 

[voner]

Mary,

The specialists familiar with this would be an electrophysiologist, cardiologist, or a neurologist with specialty in autonomic systems or a ME/CFS specialist. in the past I’ve been able to get family practitioners to prescribe it. It has side effects you need to be aware of.

 

[Mel9]

My ME CFS specialist prescribed it for me.

 

[frozenborderline]

khosro farhad prescribed it for me. going to try it and track bp /heart rate during it a little more than i normally do.

 

[valentinelynx]

I've been taking Huperzine A, a dietary supplement that is also a cholinesterase inhibitor, like pyridostigmine (Mestinon). I believe it helps me with GI motility, and possibly with clarity of thought. It is available over the counter, e.g. Amazon.

 

[kangaSue]

I've been taking Huperzine A, a dietary supplement that is also a cholinesterase inhibitor, like pyridostigmine (Mestinon). I believe it helps me with GI motility, and possibly with clarity of thought. It is available over the counter, e.g. Amazon.

Parasym Plus is another over the counter supplement that works like pyridostigmine (Mestinon) which also has Hhuperzine A as an ingredient.

 

[Mary]

Does anyone know who would be a good candidate for mestinon or huperzine A or Parasym Plus? Dr. Systrom's study design talks about small fiber polyneuropathy. I don't seem to have any symptoms of small fiber polyneuropathy, no pain. But I do suffer from PEM as predictable as clockwork when I overdo it and Dr. Systrom I think is theorizing that PEM may result from complications resulting from SFP.

A Medscape article (https://www.medscape.com/viewarticle/911666 ) states in part:

David M. Systrom, MD, a pulmonary and critical care medicine specialist and director of the Invasive Cardiopulmonary Laboratory at Brigham and Women’s Hospital (BWH), Boston, described results from invasive cardiopulmonary testing that show that patients with ME/CFS have distinct defects in both ventricular filling pressure and oxygen extraction from the muscles.

Neither of those are features of deconditioning, in which the major defect is decreased stroke volume and cardiac output. In ME/CFS patients, he found supranormal pulmonary blood flow compared with VO2 max, indicating left-to-right shunting.

In addition, Systrom found that a large proportion of ME/CFS patients with these cardiopulmonary defects also have biopsy-demonstrated small fiber polyneuropathy, suggesting that PEM may be due to an underlying autonomic nervous system dysfunction.

I have read that Mestinon can have serious side effects and I'm presuming that the Huperzine A and Parasym Plus would be better tolerated.

Anyways, does anyone have any guidance here for how I could determine whether I'd be a good candidate for one of these substances? or, is it like almost everything else with this illness - try it and see how I do? I don't seem to have OI or POTS - I've done a poor man's tilt table test which was negative, BP and HR were fine. But that same Medscape article also states:

in patients with ME/CFS who have OI, cerebral blood flow drops significantly compared with controls on tilt-table testing even without changes in heart rate or blood pressure.

Any ideas?

FWIW, I started a thread about the Medscape article (which I think is very good) here.

 

[Mary]

@Murph, @voner, @kangaSue, @valentinelynx, I meant to tag several of you in my post above but my laptop had different ideas! So am tagging you here re the above post -

 

[kangaSue]

Does anyone know who would be a good candidate for mestinon or huperzine A or Parasym Plus? Dr. Systrom's study design talks about small fiber polyneuropathy. I don't seem to have any symptoms of small fiber polyneuropathy, no pain. But I do suffer from PEM as predictable as clockwork when I overdo it and Dr. Systrom I think is theorizing that PEM may result from complications resulting from SFP.

You don't necessarily get significant pain with SFN or Autonomic Neuropathy and if you feel like crap from heat or being out in the sun and/or you have a mild burning or tingly feeling in your feet and maybe calves too, even if it's only when you or the weather are hot, this can be SFN.

Chances are that you will have abnormal results in doing a QSART sweat test (sudomotor dysfunction - reduced sweating) and a Heart Rate Variability to Deep Breathing test too (cardiovagal dysfunction).

With sudomotor dysfunction, you can feel like you sweat normally but actually have reduced sweat function. A Thermoregulatory Sweat Test (in a temperature controlled chamber or room) is another test that checks how much you actually sweat in response to heat if the cholinergic agonists used in a QSART test is likely to cause you grief.

Anyways, does anyone have any guidance here for how I could determine whether I'd be a good candidate for one of these substances?

Chronic constipation can be due to autonomic dysfunction so if you suffer from this, a test you can do yourself is to place a nicotine patch over the position of the ileocecal valve and if you have a bowel motion within in a couple of hours, these substances could be beneficial.

 

[Mary]

Chances are that you will have abnormal results in doing a QSART sweat test (sudomotor dysfunction - reduced sweating) and a Heart Rate Variability to Deep Breathing test too (cardiovagal dysfunction).

Thanks @kangaSue! I've known for years that I sweat very little. I live where it routinely gets over 100 in the summer, and I barely break a sweat - I hardly need deodorant. What kind of doctor would order a sweat test? I do like heat though. I much prefer it to cold.

I'm assuming a cardiologist would order a Heart Rate Variability to Deep Breathing test.

I don't have constipation - my digestion overall is good and I know I'm very fortunate with that compared to so many here!

 

[kangaSue]

Thanks @kangaSue! I've known for years that I sweat very little. I live where it routinely gets over 100 in the summer, and I barely break a sweat - I hardly need deodorant. What kind of doctor would order a sweat test? I do like heat though. I much prefer it to cold.

I'm assuming a cardiologist would order a Heart Rate Variability to Deep Breathing test.

I don't have constipation - my digestion overall is good and I know I'm very fortunate with that compared to so many here!

Autonomic dysfunction is very common in many autoimmune conditions so any doctor seeingautoimmune condition patients can order any if this testing.

I had an autonomic function test panel done through the Neurology Dept at my local tertiary hospital which has a dedicated autonomic function testing lab. My GI actually made the referral for the testing.

Cardiologists can order a HRVDB test for sure.Tthere are portable devices around for doing just QSART and HRVDB tests which some Physicians (in the U.S.A. anyway) might have in their office, otherwise, also look for a specialist Autonomic Function Test Centre too.

If you hardly sweat though, I think there's a high probability that SFN or Autonomic Neuropathy is involved and it's worth trying Mestinon (that's what I was prescribed) or these supplements.

Mestinon helped me in improving the sweat response but caused of worsening of GI pain and the GI pain was the main issue that I was hoping to fix from it.

 

[Mary]

@kangaSue - thanks for all the info!

 

[rel8ted]

Autonomic dysfunction is very common in many autoimmune conditions so any doctor seeing autoimmune condition patients can order any if this testing.

My neuro ordered a full autonomic workup on me. There is actually only 1 doctor in the entire state that has the equipment to do all of the testing. I would hope the QSART is more readily available, though. Some neuros with an interest in dysautonomias may have equipment for these test, depending on which cinditions they are interested in.

 

[Mary]

Well, being a little impatient but also not feeling up to the amount of work and effort and time and appointments which would be required to just find a doctor who would be interested enough and able to get some of this testing done, I've just ordered some Huperzine A. I've read several reviews and for many people it's very powerful, and not always in a pleasant way, though sometimes it is. So I will definitely start very low and go slowly with it.

There is a very good endo I'm planning on seeing. It will take effort to see him (2 hour drive, etc.) but from what I read and have heard, he will be worth it and I would bet that he could make appropriate referrals if he thought more testing was warranted. But there's about a 2-month wait to see him (which is not bad at all!) so in the meanwhile I'll do a little huperzine a experiment.

 

[sb4]

@Mary I took some Huperzine A / Parasymplus a few years back when I was at my worst. Noticed nothing at small doses, and a significant worsening at high dose that took a week to wear off. Other people have had success however.

 

[Mary]

@sb4 - thanks for sharing your experience - It's such a crap shoot! I'm glad the bad effects wore off in a week - I can handle losing a week of my life, have done it many times! And apparently one gets results pretty quickly, good or bad, and it's one of the cheaper things to try. But I will be very careful with it!