The LIFT trial (OMF) - Pyridostigmine (mestinon) and Low Dose Naltrexone (LDN)

[EndME]

It's on there: https://clinicaltrials.gov/study/NCT06366724

Thanks! So it seems one can find it if one searches for "ME/CFS" but not when one searches for "Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" or "Myalgic Encephalomyelitis".

 

[forestglip]

Pyridostigmine and low-dose naltrexone for ME/CFS: study protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial

Danielle Meadows, Johanna Squires, Joshua Dibble, Shreya Palwayi, Donna Felsenstein, Linda Tannenbaum, Peng Li, Wenzhong Xiao, Jonas Bergquist, David Systrom

Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic disease with no FDA-approved treatments. This report describes a protocol for the Life Improvement Trial (LIFT), a randomized, double-blind, placebo-controlled clinical trial investigating the impact of low-dose naltrexone (LDN) and pyridostigmine (Mestinon) on physiological response, symptoms, and functionality of ME/CFS patients.

Methods
Participants (target n = 160) are recruited through clinics at Massachusetts General Hospital and Brigham and Women’s Hospital, and through Open Medicine Foundation’s StudyME registry. They are then randomized into one of four arms: LDN/pyridostigmine, LDN/placebo, placebo/pyridostigmine, placebo/placebo. Treatment is administered for 13 weeks after an initial screening period of up to 4 weeks. Primary outcomes are FUNCAP-55 score, peak oxygen utilization, heart rate recovery, and oxygen uptake efficiency slope. Secondary outcomes are scores from DSQ-PEM and PROMIS-29 surveys, DANA Brain Vital score, step count, heart rate, and heart rate variability.

Discussion
The results of this trial will provide novel insights into the efficacy of and predictors of response to LDN and pyridostigmine in ME/CFS. This may inform future treatment strategies for ME/CFS. The trial will also validate what primary and secondary outcomes to use in similar clinical trials.

Trial registration
This trial was registered on clinicaltrials.gov (NCT06366724) on April 16, 2024.

Link | PDF (Preprint: Research Square) [Open Access]

 

[shak8]

Too bad each randomized group can't be rotated through all four arms of the trial.

 

[Utsikt]

Subjects who complete the trial are also permitted to keep their Garmin watch.​

Garmin Vivosmart 5 go for ~$150. They receive up to an additional $250 if they complete all steps.

$400 per person seems like a relatively cheap way to hedge against dropouts considering the cost of running trials.

 

[Trish]

Too bad each randomized group can't be rotated through all four arms of the trial.

I guess that depends whether they are looking for immediate effects or gradual or long term effects. If only immediate effects, such as testing a pain killer, then rotating them makes sense. If the treatment is aimed at, for example, long term elimination of PEM that only be judged over several years, then switching would make it impossible to tell which drug was effective.

 

[wigglethemouse]

Update on LIFT trial from David Systrom. He also talks about data from a retrospective analysis of patients using these drugs in the clinic. (Shoutout to post by @voner )

 

[ChronicallyOverIt]

Jarod Younger (brain 'on fire' guy) did a small study in 2014 and found that LDN helps with pain syndromes.

Was just reading this letter that says Jarred Younger over hyped those results:

Low-dose naltrexone for fibromyalgia: a re-analysis suggests lower efficacy than previously reported - PMC

pmc.ncbi.nlm.nih.gov

Dumb question but is this trial have just LDN and just mestinon arms? To me it looks like the participants take both? I really like this trial to sort out if LDN does anything so we can move on

 

[Felis Catus]

Dumb question but is this trial have just LDN and just mestinon arms? To me it looks like the participants take both? I really like this trial to sort out if LDN does anything so we can move on

Do you mean the LIFT trial?

This double-blind, placebo-controlled study will involve 160 participants randomized into one of four possible groups: Pyridostigmine/LDN (40), Pyridostigmine/Placebo (40), LDN/Placebo (40), Placebo/Placebo (40). The dose of Pyridostigmine will be carefully titrated from 30mg to 60mg three times a day, and the dose of LDN will be titrated from 1.5 mg to 4.5 mg once daily.

So there is an arm with both, with LDN only, pyridostigmine only and placebo.

 

[V.R.T.]

I really like this trial to sort out if LDN does anything so we can move on

Me too. Or if either or the combination does turn out to do anything, so I can try it knowing that I'm not just risking nasty side effects and possible deterioation for nothing.

 

[ChronicallyOverIt]

Do you mean the LIFT trial?


So there is an arm with both, with LDN only, pyridostigmine only and placebo.

Yes! Sorry was late last night reading that now makes sense.

I also see that BC women’s in Canada is doing an LDN only:

ClinicalTrials.gov

clinicaltrials.gov

So we should finally have lots of placebo controlled data.

 

[Dolphin]

Yes! Sorry was late last night reading that now makes sense.

I also see that BC women’s in Canada is doing an LDN only:

ClinicalTrials.gov

clinicaltrials.gov

So we should finally have lots of placebo controlled data.

The BC study is the one funded by the (UK) ME Association.

 

[forestglip]

The BC study is the one funded by the (UK) ME Association.

Some posts about this trial have been moved to the thread for the trial: Trial registration: Low-dose Naltrexone for Post-COVID Fatigue Syndrome, 2022, Luis Nacul, British Columbia Women's Hospital & Health Centre