LIFT: Life Improvement Trial

NCT06366724 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 2024P000087
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

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 18-70 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.

Conditions

ME/CFS; Long COVID; PASC

Keywords

Chronic fatigue; Mestinon; Low Dose Naltrexone; Orthostatic Intolerance; Post exertional malaise; Cognitive Impairment; Long COVID

Outcome Measures

Primary Outcomes (4)

• Functional Capacity

  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.

  15 weeks

• Physiologic Response - Oxygen Uptake Efficiency Slope (OUES)

  Changes in % of predicted oxygen uptake efficiency slope (OUES) between baseline and follow-up measured during a non-invasive cardiopulmonary exercise test (CPET)

  13 weeks

• Physiologic Response - Oxygen Utilization (VO2)

  Changes in % of predicted extrapolated peak oxygen utilization (extrapolated max VO2) between baseline and follow-up measured during a submaximum CPET

  13 weeks

• Physiologic Response - Heart Rate Recovery (HRR)

  Changes in 1-min heart rate recovery (HRR) in beats per minute (bpm) between baseline and follow-up measured during a submaximum CPET

  13 weeks

Secondary Outcomes (9)

• Post-Exertional Malaise

  15 weeks

• PROMIS-29-Pain

  15 weeks

• Daily Activity

  15 weeks

• Heart Rate Variability

  15 weeks

• Blood Oxygen

  15 weeks

Study Arms (4)

Pyridostigmine/LDN

ACTIVE COMPARATOR

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).

Drug: Pyridostigmine; Drug: Low-Dose Naltrexone

Pyridostigmine/Placebo

ACTIVE COMPARATOR

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.

Drug: Pyridostigmine; Other: Placebo

Placebo/LDN

ACTIVE COMPARATOR

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).

Drug: Low-Dose Naltrexone; Other: Placebo

Placebo/Placebo

PLACEBO COMPARATOR

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 .

Other: Placebo

Interventions

Pyridostigmine DRUG

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)

Also known as: Mestinon

Pyridostigmine/LDN; Pyridostigmine/Placebo

Low-Dose Naltrexone DRUG

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)

Also known as: LDN

Placebo/LDN; Pyridostigmine/LDN

Placebo OTHER

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)

Placebo/LDN; Placebo/Placebo; Pyridostigmine/Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Open Medicine Foundation: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Links

• MGB Rally - LIFT

MeSH Terms

Conditions

Fatigue Syndrome, Chronic; Post-Acute COVID-19 Syndrome; Orthostatic Intolerance; Cognitive Dysfunction

Interventions

Pyridostigmine Bromide; Naltrexone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Primary Dysautonomias; Autonomic Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• David Systrom, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Coordinator

CONTACT

617-525-6797; jsquires1@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator; Director, Dyspnea Center; Associate Professor of Medicine

Model Details: Randomized factorial group double-blinded placebo-controlled trial

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: April 16, 2024
• Study Start: September 10, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: October 22, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF, CSR
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Proposals should be directed to jsquires1@bwh.harvard.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)