Simmaron research start new rapamycin trial

[Murph]

https://www.simmaronresearch.com/rapamycin-trial

The First Biomarker-Driven Treatment Trial for ME/CFS​

Subsets Mean Success​

Until now, the heterogeneity of the patient population and the lack of a reliable biomarker to diagnose and prognose ME/CFS has thwarted clinical trials for both non-approved FDA drugs as well as repurposed agents.
We have recently identified elevated levels of inactive ATG-13 as a testable and targetable pathway for treating symptoms of post-exertional malaise.

Biomarker to Treatment Trial​

Rapamycin therapy inhibits mTOR and reduces autophagy disruption. We believe that a subset of patients may have chronic mTOR activation that can lead to the symptoms of ME/CFS. By taking rapamycin, the mTOR inhibitor, we hope that these people may see a significant reduction in symptoms.

We will track symptoms and autophagy markers in this study

Why Rapamycin​

Our publication on elevated ATG13 showed that a significant number of ME/CFS patients display serological evidence of autophagy disruption. We have shown that this deficit in autophagy is due to the chronic activation of mTOR. Without properly functioning autophagy, there is significant cellular stress, immune activation, and not enough energy for the cell to do well.
Rapamycin is an mTOR inhibitor. It is an FDA approved drug that was initially developed to protect patients during a kidney transplant. It has a well understood safety profile. This study will track autophagy markers and ME/CFS symptoms in patients who are treated with low-dose rapamycin by participating clinicians.

Our Goal​

One goal is to identify and characterize a subset of patients who are likely to respond to this potential treatment. We also intend to submit a grant for an NIH exploratory treatment trial depending on data generated in this pilot study. This is a big step in Simmaron’s overarching goal of spurring more treatment trials for ME/CFS patients who have waited far too long.

Participating Clinicians​

David Kaufman MD
Center for Complex Diseases, lead clinician
Daniel Peterson MD
Sierra Internal Medicine
Bela Chedda MD
Center for Complex Diseases at Stanford

Simmaron’s Role​

The Simmaron Research and Development lab at UWM is responsible for studying the blood and questionnaires. We hypothesize that ME/CFS patients with elevated serum levels of pATG-13 and related autophagy disruption markers who are given low dose rapamycin will have these proteins (ATG-13) normalize and this may trend with a reduction in ME/CFS symptoms including PEM flairs. Our role is to collect and analyze data tracking symptoms and autophagy.
We are also grateful for the collaboration of the Milwaukee Institute of Drug Discovery (MIDD), University of Wisconsin-Milwaukee (UWM), Indiana Health University ICBI.

• In order to enroll in this trial you must be a patient under the care of the participating clinicians: Dr. David Kaufman MD, Dr. Daniel Peterson MD, Dr. Bela Chedda MD, and Dr. Stephanie Grach MD. If you are on Rapamycin and have ME/CFS, or you have been told by your doctor that they plan to start you on Rapamycin, please email connect@simmaron.com.
  
• 18-65 years old, ME/CFS patient of a participating clinician.
  *We will also recruit ME/CFS patients who are on other therapies or on no therapies at all as a comparison group.

• One hundred patients will be enrolled.
  

• This is a pilot study to observe the effects of low dose rapamycin treatment, and to determine the incidence of elevated levels of inactive ATG-13 and other autophagy proteins before, during and after treatment.
  
  
  
• We are estimating that it will take approximately 18 months - 2 years to enroll our goal of 100 patients and aggregate results. Once we have results, we will seek to publish them and inform the community.

 

[SlamDancin]

Well we’ve seen this idea come full circle. Feels good. Hope it gives good data and helps some patients. Dr Kaufman was my doctor when we first started throwing around Rapa as a treatment on here and he was supportive of my trial at the time. Good to see he’s involved here although unfortunately I’m no longer a patient so I won’t be in this trial.

 

[Dude]

Is there a approximate number % of affected people who have elevated ATG13?

 

[Murph]

Is there a approximate number % of affected people who have elevated ATG13?

They found it high in most. All patients(red dots) were higher than the healthy mean.

This is 10 patients vs 10 controls from their published paper. Some overlap which is presumably why they're saying it might work only for a subset.

 

[SlamDancin]

@Murph Any opinion on the way the trial is going to be conducted? There were some concerns I saw posted on S4ME

 

[Murph]

@Murph Any opinion on the way the trial is going to be conducted? There were some concerns I saw posted on S4ME

it isn't on clinicaltrials.gov yet which does looks a teensy bit amateur hour.

My sense is if you want to skip the bureaucracy you are smarter pretending you're not planning a trial like this and then retrospectively analysing the charts of 100 patients who "just happened" to be treated at the clinic with the same drug and given the same tests. And discovering a pattern that way. Prospectively announcing a clinical trial but not registering it is a bit odd.

I hope their approach doesn't pose any problems because the trade off is it should be faster than going thru official channels.

 

[Rachel Riggs]

I'm starting rapamycin tomorrow, along with an ME friend. We got the dosing schedule from someone who's in the study and I ordered it online. Fingers crossed.

 

[Sushi]

I'm starting rapamycin tomorrow, along with an ME friend. We got the dosing schedule from someone who's in the study and I ordered it online. Fingers crossed.

Good luck Rachel. This is an interesting one. Please keep us posted, 🤞🏼

 

[Anish04]

I have Also bought 1 mg sirolimus tablets (24 of them). But don't know about dosing protocol.i remember it was something like 6 mg weekly

 

[Rachel Riggs]

I have Also bought 1 mg sirolimus tablets (24 of them). But don't know about dosing protocol.i remember it was something like 6 mg weekly

I plan to start at 1mg once weekly and titrate up, adding an additional 1 mg each week until I get to 6mg, or determine where the sweet spot lies.

 

[joshualevy]

it isn't on clinicaltrials.gov yet which does looks a teensy bit amateur hour.

My sense is if you want to skip the bureaucracy you are smarter pretending you're not planning a trial like this and then retrospectively analysing the charts of 100 patients who "just happened" to be treated at the clinic with the same drug and given the same tests. And discovering a pattern that way. Prospectively announcing a clinical trial but not registering it is a bit odd.

I hope their approach doesn't pose any problems because the trade off is it should be faster than going thru official channels.

The impact of doing it the way Murth describes is three fold:
1. Retrospective studies are well known to be much lower quality than prospective. So other researchers are going to consider any such study to be much worse than any prospective study.
2. The FDA has various requirements to approve a drug or to approve it for a new use. Those requirements are all based on prospective studies. Retrospective studies don't count as the core support of getting the FDA to approve something.
3. Also, the FDA has a very specific requirement that studies used to approve or extend drug use must be registered ahead of time on clinicaltrials.gov.

Of course, none of this matters if your goal publicity. If you want to get doctors to proscribe this drug "off label" then you can do it with unregistered, retrospective studies. However, if your goal is to get a drug approved or a new use case added to the official indications, then you need registered, prospective clinical trials.

 

[Rachel Riggs]

I got my Rapamycin through Healthspan.com. The bottle lists Dr. Reddy's (India) as the manufacturer and GoGoMeds as the US pharmacy who filled the Rx. I'm going to see if I can purchase direct as Healthspan charges $145 per month.

 

[Inez]

Hi @Rachel Riggs have how is your rapamycin trial going? Have you or your friend had any improvement?

 

[cfs since 1998]

I'm a bit concerned about the side effects of this drug. One of them being possibly endothelial dysfunction (for example, Reineke 2015). I personally would not feel comfortable trying this until we get some results from Simmaron's trial.