Clinical trial NCT06366724: LIFT: Life Improvement Trial
Official title: LIFT: Life Improvement Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: ME/CFS
Keywords: Chronic fatigue
Mestinon
Low Dose Naltrexone
Orthostatic Intolerance
Post exertional malaise
Cognitive Impairment
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Open Medicine Foundation
First posted: 2024-04-16
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Randomized factorial group double-blinded placebo-controlled trial
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 ≤ 65 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.

Primary outcomes:
measure: Functional Capacity
timeFrame: 15 weeks
measure: Physiologic Response - Oxygen Uptake Efficiency Slope (OUES)
timeFrame: 13 weeks
measure: Physiologic Response - Oxygen Utilization (VO2)
timeFrame: 13 weeks
measure: Physiologic Response - Heart Rate Recovery (HRR)
timeFrame: 13 weeks
Secondary outcomes:
measure: Post-Exertional Malaise
timeFrame: 15 weeks
measure: PROMIS-29-Pain
timeFrame: 15 weeks
measure: Daily Activity
timeFrame: 15 weeks
measure: Heart Rate Variability
timeFrame: 15 weeks
measure: Blood Oxygen
timeFrame: 15 weeks
measure: Resting Heart Rate
timeFrame: 15 weeks
measure: DANA Brain Vital-Simple Reaction Time (SRT)
timeFrame: 15 Weeks
measure: DANA Brain Vital-Procedural Reaction Time (PRT)
timeFrame: 15 weeks
measure: DANA Brain Vital-Memory Search (MS)
timeFrame: 15 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Mass General Brigham
name: David Systrom, MD
role: PRINCIPAL_INVESTIGATOR
References: