LIFT: Life Improvement Trial
- Conditions
- ME/CFS
- Interventions
- Registration Number
- NCT06366724
- Lead Sponsor
- Brigham and Women's Hospital
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
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Meet National Academy of Medicine Criteria, Canadian Consensus Criteria (See appendix), and demonstrate orthostatic intolerance for diagnosis of ME/CFS
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Participant is ≥ 18 and ≤ 65 years of age at screening, inclusive.
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The onset of symptoms prior to December 2023.
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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.
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Participant agrees and can adhere to the study requirements for the length of the study.
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Participant has a body mass index (BMI) range of 17 to 40 kg/m2, inclusive.
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Participant agrees not to participate in another interventional study while participating in the present study.
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Participant has a functioning smart phone to download and run the DANA Brain Vital Mobile Application.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Pyridostigmine/LDN Low-Dose Naltrexone Pyridostigmine will be taken as liquid suspension three times a day, scaling up from 20mg (1.67mL) to 60mg (5mL) (180mg/day). Low dose naltrexone will be taken as liquid suspension once a day, scaling up from 1.5mL to 4.5mL (4.5mg/day). Pyridostigmine/Placebo Placebo Pyridostigmine will be taken as liquid suspension three times a day, scaling up from 20mg (1.67mL) to 60mg (5mL) (180mg/day). Placebo will be taken as liquid suspension once a day, scaling up from 1.5mL to 4.5mL. Placebo/LDN Low-Dose Naltrexone Placebo will be taken as liquid suspension three times a day, scaling up from 1.67mL to 5mL. Low dose naltrexone will be taken as liquid suspension once a day, scaling up from 1.5mL to 4.5mL (4.5mg/day). Placebo/LDN Placebo Placebo will be taken as liquid suspension three times a day, scaling up from 1.67mL to 5mL. Low dose naltrexone will be taken as liquid suspension once a day, scaling up from 1.5mL to 4.5mL (4.5mg/day). Placebo/Placebo Placebo Placebo will be taken as liquid suspension three times a day, scaling up from 1.67mL to 5mL. Placebo will be taken as liquid suspension once a day, scaling up from 1.5mL to 4.5mL . Pyridostigmine/LDN Pyridostigmine Pyridostigmine will be taken as liquid suspension three times a day, scaling up from 20mg (1.67mL) to 60mg (5mL) (180mg/day). Low dose naltrexone will be taken as liquid suspension once a day, scaling up from 1.5mL to 4.5mL (4.5mg/day). Pyridostigmine/Placebo Pyridostigmine Pyridostigmine will be taken as liquid suspension three times a day, scaling up from 20mg (1.67mL) to 60mg (5mL) (180mg/day). Placebo will be taken as liquid suspension once a day, scaling up from 1.5mL to 4.5mL.
- Primary Outcome Measures
Name Time Method Functional Capacity 15 weeks 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 Utilization (VO2) 13 weeks 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) 13 weeks Changes in 1-min heart rate recovery (HRR) in beats per minute (bpm) between baseline and follow-up measured during a submaximum CPET
Physiologic Response - Oxygen Uptake Efficiency Slope (OUES) 13 weeks Changes in % of predicted oxygen uptake efficiency slope (OUES) between baseline and follow-up measured during a non-invasive cardiopulmonary exercise test (CPET)
- Secondary Outcome Measures
Name Time Method Resting Heart Rate 15 weeks Change in resting heart rate (bpm) using Garmin VivoSmart 5
Blood Oxygen 15 weeks Change in blood oxygen saturation (%) measured with Garmin VivoSmart 5
DANA Brain Vital-Simple Reaction Time (SRT) 15 Weeks Change in time (ms) required to recognize the presence of an object and tap the object
DANA Brain Vital-Procedural Reaction Time (PRT) 15 weeks Change in time (ms) required to recognize 1 of 4 numbers and tap 1 of 2 buttons
Post-Exertional Malaise 15 weeks 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.Daily Activity 15 weeks Change in daily steps (steps/day) measured using Garmin Vivosmart 5
Heart Rate Variability 15 weeks Change in heart rate variability (HRV) defined as the specific change in time (ms) between successive heart beats. All collected via Garmin VivoSmart5
DANA Brain Vital-Memory Search (MS) 15 weeks Change in time (ms) required to recognize letters that have previously been memorized
PROMIS-29-Pain 15 weeks 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.
Trial Locations
- Locations (1)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States