LIFT: Life Improvement Trial

Overview

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.

Interventions

• 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)
• 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 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)

Primary outcome measures

• Functional Capacity [Time frame: 15 weeks]
• Physiologic Response - Oxygen Uptake Efficiency Slope (OUES) [Time frame: 13 weeks]
• Physiologic Response - Oxygen Utilization (VO2) [Time frame: 13 weeks]
• Physiologic Response - Heart Rate Recovery (HRR) [Time frame: 13 weeks]

Secondary outcome measures (9)

• Post-Exertional Malaise [Time frame: 15 weeks]
• PROMIS-29-Pain [Time frame: 15 weeks]
• Daily Activity [Time frame: 15 weeks]
• Heart Rate Variability [Time frame: 15 weeks]
• Blood Oxygen [Time frame: 15 weeks]
• Resting Heart Rate [Time frame: 15 weeks]
• DANA Brain Vital-Simple Reaction Time (SRT) [Time frame: 15 Weeks]
• DANA Brain Vital-Procedural Reaction Time (PRT) [Time frame: 15 weeks]
• DANA Brain Vital-Memory Search (MS) [Time frame: 15 weeks]

Eligibility criteria

Inclusion criteria

• 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.
• Female participant is not pregnant and at least 1 of the following conditions apply:

• Not a woman of childbearing potential
• Woman of childbearing potential who agrees to follow the contraceptive guidance. from the time of informed consent.
• Participant agrees and can adhere to the study requirements for the length of the study.
• Participant has a body mass index (BMI) range of 17 to 40 kg/m2, inclusive.
• Participant agrees not to participate in another interventional study while participating in the present study.
• Participant has a functioning smart phone to download and run the DANA Brain Vital Mobile Application.

Exclusion criteria

• 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
• Participation in another interventional clinical trial in the last 30 days or planned during the trial period.
• Allergy to medication components
• Participant has any condition which, in the investigator's opinion, makes the participant unsuitable for study participation.
• Participant has diabetes mellitus (type 1 or 2).
• 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.
• 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)
• Participant has an active malignancy or any other cancer.
• Participant has initiated an exercise regimen within 4 weeks prior to randomization.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Brigham and Women's Hospital — Boston

Identifiers

NCT: NCT06366724 · 2024P000087

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗