Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Long COVID.

The Life Improvement Trial (LIFT)

The Life Improvement Trial (LIFT) aims to investigate two drugs, separately and in combination, Pyridostigmine (commonly known as Mestinon) and Low-Dose Naltrexone (LDN), for efficacy and to research the difference between responders and non-responders.

  • David Systrom, MD, Director of OMF’s Harvard Collaboration
  • Jonas Bergquist, MD, PhD, OMF’s Chief Medical Officer and Director of the Uppsala University Collaboration

The LIFT represents a significant endeavor to improve treatment options for ME/CFS patients and contribute to the broader understanding of this debilitating condition.

Clinical Trial Description

The lift trial two lead researcher headshots.The LIFT will be conducted at Brigham and Women’s Hospital (BWH) of Harvard Medical School, focusing on the effect of Pyridostigmine (Mestinon) and Low-Dose Naltrexone (LDN) in subjects aged 18-65 meeting the Canadian consensus criteria (CCC) for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) as well as having specifically Orthostatic Intolerance. Both drugs may be anti-inflammatory, LDN through the blockage of toll-like receptors, and Pyridostigmine through its cholinergic effects.

This double-blind, placebo-controlled study will involve 160 participants randomized into one of four possible arms: 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.

The trial includes a scale-back plan, allowing participants to reduce their dosage if they experience intolerance symptoms, with adjustments made during weekly visits. This plan provides a personalized approach to medication tolerance, ensuring participant’s safety and comfort throughout the trial.

The time commitment for the participant is approximately three (3) months, and during this time, there will be three (3) in-person visits to BWH and four (4) virtual visits. Study procedures will include two (2) submaximum cardiopulmonary exercise tests, questionnaires (virtually completed), and blood and urine collection. We will be recruiting from the BWH Dyspnea Clinic as well as the OMF StudyME Registry and anticipate the entire trial will take two (2) years to complete.

OBJECTIVES
  • Gain insights into ME/CFS pathogenesis by evaluating the effects of Pyridostigmine and LDN treatments.
  • Investigate the synergistic effect of the two medications, Pyridostigmine and LDN, when used in combination.
  • Identify which people with ME/CFS are likely to benefit from Pyridostigmine and LDN treatments.
  • Delve into the patient’s physiology with proteomics, metabolomics, and other assessments to find biomarkers that identify responders and enhance the understanding of ME/CFS.
  • Discover a biomarker or biomarker signature that differentiates people with ME/CFS from healthy individuals.
  • Inform the scientific and medical communities about ME/CFS pathogenesis through treatment and testing results.
  • Enable the widespread use of Pyridostigmine and LDN by primary care doctors.
  • Establish the infrastructure necessary for future clinical treatment trials funded by OMF.

Learn more about the LIFT!