protocolSection identificationModule nctId: NCT06366724, orgStudyIdInfo id: 2024P000087, briefTitle: LIFT: Life Improvement Trial, acronym: LIFT, statusModule overallStatus: NOT_YET_RECRUITING, startDateStruct date: 2024-07, primaryCompletionDateStruct date: 2026-03, completionDateStruct date: 2026-06, studyFirstPostDateStruct date: 2024-04-16, lastUpdatePostDateStruct date: 2024-04-16, sponsorCollaboratorsModule leadSponsor name: Brigham and Women's Hospital, class: OTHER, collaborators name: Open Medicine Foundation, descriptionModule briefSummary: 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.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., conditionsModule conditions: ME/CFS, designModule studyType: INTERVENTIONAL, phases: PHASE2, designInfo allocation: RANDOMIZED, interventionModel: FACTORIAL, interventionModelDescription: Randomized factorial group double-blinded placebo-controlled trial, primaryPurpose: TREATMENT, maskingInfo masking: QUADRUPLE, maskingDescription: The Mass General Brigham Investigational Drug Services (IDS) will be responsible for randomizing the four arms. The rest of the study staff and collaborators will be blinded as well as the participant., whoMasked: PARTICIPANT, whoMasked: CARE_PROVIDER, whoMasked: INVESTIGATOR, whoMasked: OUTCOMES_ASSESSOR, enrollmentInfo count: 160, type: ESTIMATED, armsInterventionsModule interventions name: Pyridostigmine, interventions name: Low-Dose Naltrexone, interventions name: Placebo, outcomesModule primaryOutcomes measure: Functional Capacity, primaryOutcomes measure: Physiologic Response - Oxygen Uptake Efficiency Slope (OUES), primaryOutcomes measure: Physiologic Response - Oxygen Utilization (VO2), primaryOutcomes measure: Physiologic Response - Heart Rate Recovery (HRR), secondaryOutcomes measure: Post-Exertional Malaise, secondaryOutcomes measure: PROMIS-29-Pain, secondaryOutcomes measure: Daily Activity, secondaryOutcomes measure: Heart Rate Variability, secondaryOutcomes measure: Blood Oxygen, secondaryOutcomes measure: Resting Heart Rate, secondaryOutcomes measure: DANA Brain Vital-Simple Reaction Time (SRT), secondaryOutcomes measure: DANA Brain Vital-Procedural Reaction Time (PRT), secondaryOutcomes measure: DANA Brain Vital-Memory Search (MS), eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 65 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule, hasResults: False