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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
160
Pyridostigmine 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)
LDN 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 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)
Brigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGFunctional 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.
Time frame: 15 weeks
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)
Time frame: 13 weeks
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
Time frame: 13 weeks
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
Time frame: 13 weeks
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.
Time frame: 15 weeks
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.
Time frame: 15 weeks
Daily Activity
Change in daily steps (steps/day) measured using Garmin Vivosmart 5
Time frame: 15 weeks
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
Time frame: 15 weeks
Blood Oxygen
Change in blood oxygen saturation (%) measured with Garmin VivoSmart 5
Time frame: 15 weeks
Resting Heart Rate
Change in resting heart rate (bpm) using Garmin VivoSmart 5
Time frame: 15 weeks
DANA Brain Vital-Simple Reaction Time (SRT)
Change in time (ms) required to recognize the presence of an object and tap the object
Time frame: 15 Weeks
DANA Brain Vital-Procedural Reaction Time (PRT)
Change in time (ms) required to recognize 1 of 4 numbers and tap 1 of 2 buttons
Time frame: 15 weeks
DANA Brain Vital-Memory Search (MS)
Change in time (ms) required to recognize letters that have previously been memorized
Time frame: 15 weeks
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