ME/CFSPhase 2LIFTNCT06366724
LIFT: Life Improvement Trial
A Phase 2 study testing Pyridostigmine and Low-Dose Naltrexone in people with ME/CFS and Long COVID, run by Brigham and Women's Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- ME/CFS, Long COVID, PASC
- What is being tested?
- Pyridostigmine and Low-Dose Naltrexone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Sep 2024to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Clinical Research Coordinator, 617-525-6797, jsquires1@bwh.harvard.edu
About this study
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.
Read more
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
- Being tested
- Pyridostigmine, Low-Dose Naltrexone, Placebo
- Keywords
- Chronic fatigue, Mestinon, Low Dose Naltrexone, Orthostatic Intolerance, Post exertional malaise, Cognitive Impairment, Long COVID
- Medical subject headings
- Fatigue Syndrome, Chronic, Post-Acute COVID-19 Syndrome, Orthostatic Intolerance, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PyridostigmineDrug
Also called Mestinon
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)
Low-Dose NaltrexoneDrug
Also called LDN
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)
PlaceboOther
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)
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: 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). Receives: 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 . Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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
Measured: 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
Measured: 13 weeks
Secondary outcomes (9)
Post-Exertional Malaise
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.
Measured: 15 weeks
PROMIS-29-Pain
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.
Measured: 15 weeks
Daily Activity
Change in daily steps (steps/day) measured using Garmin Vivosmart 5
Measured: 15 weeks
Heart Rate Variability
Change in heart rate variability (HRV) defined as the specific change in time (ms) between successive heart beats. All collected via Garmin VivoSmart5
Measured: 15 weeks
Blood Oxygen
Change in blood oxygen saturation (%) measured with Garmin VivoSmart 5
Measured: 15 weeks
Resting Heart Rate
Change in resting heart rate (bpm) using Garmin VivoSmart 5
Measured: 15 weeks
DANA Brain Vital-Simple Reaction Time (SRT)
Change in time (ms) required to recognize the presence of an object and tap the object
Measured: 15 Weeks
DANA Brain Vital-Procedural Reaction Time (PRT)
Change in time (ms) required to recognize 1 of 4 numbers and tap 1 of 2 buttons
Measured: 15 weeks
DANA Brain Vital-Memory Search (MS)
Change in time (ms) required to recognize letters that have previously been memorized
Measured: 15 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2024
- Study start10 Sep 2024
- Primary completionSep 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ME/CFSStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Randomized factorial group double-blinded placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Open Medicine Foundation
- Responsible party
- Principal investigator, David Systrom, Brigham and Women's Hospital
- Investigators
- David Systrom, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06366724
- Sponsor's protocol ID
- 2024P000087
- Acronym
- LIFT
- Status last verified
- Oct 2026
- First submitted
- 20 Mar 2024
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after de-identification(text, tables, figures, and appendices) will be available for researchers who provide a methodologically sound proposal to achieve aims in the approved proposal.
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LIFT: Life Improvement Trial
- ClinicalTrials.gov ID
- NCT06366724
- Acronym / sponsor ID
- LIFT / 2024P000087
- Conditions
- ME/CFS, Long COVID, PASC
- Keywords
- Chronic fatigue, Mestinon, Low Dose Naltrexone, Orthostatic Intolerance, Post exertional malaise, Cognitive Impairment, Long COVID
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Open Medicine Foundation
- Study start
- 10 Sep 2024 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 16 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized factorial group double-blinded placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Pyridostigmine/LDN | Active comparator | Drug: Pyridostigmine, Drug: Low-Dose NaltrexonePyridostigmine 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 | Active comparator | Drug: Pyridostigmine, Other: PlaceboPyridostigmine 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 | Active comparator | Drug: Low-Dose Naltrexone, Other: PlaceboPlacebo 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 comparator | Other: PlaceboPlacebo 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 . |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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:
- Participant agrees and can adhere to the study requirements for the length of the study.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PyridostigmineAlso: MestinonPyridostigmine 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 | Pyridostigmine/LDN, Pyridostigmine/Placebo |
| Low-Dose NaltrexoneAlso: LDNLDN 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) | Drug | Placebo/LDN, Pyridostigmine/LDN |
| PlaceboPlacebo 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) | Other | Placebo/LDN, Placebo/Placebo, Pyridostigmine/Placebo |
Primary outcome
Functional Capacity
Time frame: 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 Uptake Efficiency Slope (OUES)
Time frame: 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)
Physiologic Response - Oxygen Utilization (VO2)
Time frame: 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)
Time frame: 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
9 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- MGB Rally - LIFTLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification(text, tables, figures, and appendices) will be available for researchers who provide a methodologically sound proposal to achieve aims in the approved proposal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David Systrom, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyridostigmine and Low-Dose Naltrexone in people with ME/CFS and Long COVID, run by Brigham and Women's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Research Coordinator (617-525-6797, jsquires1@bwh.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Capacity (time frame: 15 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026; AzTrials last refreshed its copy on 31 Oct 2026.