About this trial
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 18-70 meeting the Canadian consensus criteria (CCC) for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) as well as having specifically Orthostatic Intolerance (OI). Long COVID (LC) subjects will also be included if they meet CCC and have OI.
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.
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 Open Medicine Foundation (OMF) StudyME Registry and anticipate the entire trial will take two (2) years to complete.
The LIFT represents a significant endeavor to improve treatment options for ME/CFS patients and contribute to the broader understanding of this debilitating condition.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Meet National Academy of Medicine Criteria, Canadian Consensus Criteria (See appendix), and demonstrate orthostatic intolerance for diagnosis of ME/CFS
Participant is ≥ 18 and ≤ 70 years of age at screening, inclusive.
The onset of symptoms prior to December 2023.
Not a woman of childbearing potential
Disqualifiers
Pregnant, planning to become pregnant, or breastfeeding.
Any use of opioid medications within 30 days of screening.
Positive urine test for opioids
History of alcohol, opioid or other substance misuse
Trial design
Factorial
Treatments tested in this trial
Pyridostigmine
DrugPyridostigmine timeline: Weeks 0-2: 20mg TID (1.67 mL TID) Weeks 2-4: 40mg TID (3.33 mL TID) Weeks 5-13: 60mg TID (5mL TID)
Low-Dose Naltrexone
DrugLDN timeline: Weeks 0-2: 1.5mg QD (1.5mL QD) Weeks 2-4: 3.0mg QD (3.0mL QD) Weeks 5-13: 4.5mg QD (4.5mL QD)
Placebo
Other interventionPlacebo timeline: Weeks 0-2: 20mg TID (1.67mL TID)/1.5mg QD (1.5mL QD) Weeks 2-4: 40mg TID (3.33mL TID)/3.0mg QD (3.0mL QD) Weeks 5-13: 60mg TID (5mL TID)/4.5mg QD (4.5mL QD)
Treatment groups
Trial outcomes
Primary outcomes
Functional Capacity
Change in the total FUNCAP55 questionnaire score The FUNCAP55 is a questionnaire developed to assess the functional capacity of patients. Each question is answered on a 6-point scale. The greater the score, the better the functioning.
Physiologic Response - Oxygen Uptake Efficiency Slope (OUES)
Changes in % of predicted oxygen uptake efficiency slope (OUES) between baseline and follow-up measured during a non-invasive cardiopulmonary exercise test (CPET)
Physiologic Response - Oxygen Utilization (VO2)
Changes in % of predicted extrapolated peak oxygen utilization (extrapolated max VO2) between baseline and follow-up measured during a submaximum CPET
Physiologic Response - Heart Rate Recovery (HRR)
Changes in 1-min heart rate recovery (HRR) in beats per minute (bpm) between baseline and follow-up measured during a submaximum CPET
Secondary outcomes
Post-Exertional Malaise
Change in DePaul Symptom Questionnaire-1 (DSQ1) score The questionnaire lists 5 symptoms that are scored based on frequency and severity. Each question is answered on a 4-point scale. The greater the score, the greater the frequency and severity of the symptom.
PROMIS-29-Pain
Change in PROMIS-29 questionnaire score Reflected as combination of the "pain interference" (0 to 5) and "pain intensity" (0 to 10) sections of the questionnaire will be secondary outcomes. The greater the score, the greater the pain experienced.
Daily Activity
Change in daily steps (steps/day) measured using Garmin Vivosmart 5
Heart Rate Variability
Change in heart rate variability (HRV) defined as the specific change in time (ms) between successive heart beats. All collected via Garmin VivoSmart5
Sponsors and contacts
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Brigham and Women's Hospital
Lead sponsor
Open Medicine Foundation
Collaborator