The LIFT will be conducted at Brigham and Women's Hospital (BWH) of Harvard MedicalSchool, focusing on the effect of Pyridostigmine (Mestinon) and Low-Dose Naltrexone (LDN)in subjects aged 18-70 meeting the Canadian consensus criteria (CCC) for MyalgicEncephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) as well as having specificallyOrthostatic Intolerance (OI). Long COVID (LC) subjects will also be included if they meetCCC and have OI.This double-blind, placebo-controlled study will involve 160 participants randomized intoone of four possible groups: Pyridostigmine/LDN (40), Pyridostigmine/Placebo (40),LDN/Placebo (40), Placebo/Placebo (40). The dose of Pyridostigmine will be carefullytitrated from 30mg to 60mg three times a day, and the dose of LDN will be titrated from1.5 mg to 4.5 mg once daily.The trial includes a scale-back plan, allowing participants to reduce their dosage ifthey experience intolerance symptoms, with adjustments made during weekly visits. Thisplan provides a personalized approach to medication tolerance, ensuring participant'ssafety and comfort throughout the trial.The time commitment for the participant is approximately three (3) months, and duringthis 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 berecruiting 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/CFSpatients and contribute to the broader understanding of this debilitating condition.
Not Provided
Drug: Pyridostigmine
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)
Other Name: Mestinon
Drug: Low-Dose Naltrexone
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)
Other Name: LDN
Other: Placebo
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)
Inclusion Criteria:
1. Meet National Academy of Medicine Criteria, Canadian Consensus Criteria (See
appendix), and demonstrate orthostatic intolerance for diagnosis of ME/CFS
2. Participant is ≥ 18 and ≤ 70 years of age at screening, inclusive.
3. The onset of symptoms prior to December 2023.
4. Female participant is not pregnant and at least 1 of the following conditions apply:
1. Not a woman of childbearing potential
2. Woman of childbearing potential who agrees to follow the contraceptive
guidance. from the time of informed consent.
5. Participant agrees and can adhere to the study requirements for the length of the
study.
6. Participant has a body mass index (BMI) range of 17 to 40 kg/m2, inclusive.
7. Participant agrees not to participate in another interventional study while
participating in the present study.
8. Participant has a functioning smart phone to download and run the DANA Brain Vital
Mobile Application.
Exclusion Criteria:
1. Pregnant, planning to become pregnant, or breastfeeding.
2. Any use of opioid medications within 30 days of screening.
3. Positive urine test for opioids
4. History of alcohol, opioid or other substance misuse
5. Participation in another interventional clinical trial in the last 30 days or
planned during the trial period.
6. Allergy to medication components
7. Participant has any condition which, in the investigator's opinion, makes the
participant unsuitable for study participation.
8. Participant has diabetes mellitus (type 1 or 2).
9. Participant has undergone an inpatient hospitalization within the 30 days prior to
the randomization or has a planned hospitalization or a surgical procedure during
the study, which may affect the study assessments, in the opinion of the
investigator.
10. Participant has clinically significant respiratory disease (such as chronic
obstructive pulmonary disease, cystic fibrosis, severe asthma, lung infections
including tuberculosis, sarcoidosis, thoracic endometriosis, pulmonary fibrosis, and
lung cancers) and/or cardiac disease (medical history or current clinical findings)
11. Participant has an active malignancy or any other cancer.
12. Participant has initiated an exercise regimen within 4 weeks prior to randomization.
Brigham and Women's Hospital
Boston 4930956, Massachusetts 6254926, United States
Investigator: Clinical Research Coordinator
Contact: 617-525-6797
jsquires1@bwh.harvard.edu
Research Coordinator
617-525-6797
jsquires1@bwh.harvard.edu
David Systrom, MD, Principal Investigator
Massachusetts General Hospital