LIFT: Life Improvement Trial

ME/CFS Clinical Trial

— LIFT  

Official title:

LIFT: Life Improvement Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06366724
• Other study ID #: 2024P000087
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: Brigham and Women's Hospital
• Contact: Research Coordinator
• Phone: 617-525-6797
• Email: jsquires1[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 18-65 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: June 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 2019.

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.

Related Conditions & MeSH terms

• Fatigue Syndrome, Chronic
• ME/CFS

Intervention

Drug:
• Pyridostigmine
Pyridostigmine timeline: Weeks 0-2: 20mg TID (1 cap TID) Weeks 2-4: 40mg TID (2 caps TID) Weeks 5-13: 60mg TID (3 caps TID)
• Low-Dose Naltrexone
LDN timeline: Weeks 0-2: 1.5mg QD (1 cap QD) Weeks 2-4: 3.0mg QD (2 caps QD) Weeks 5-13: 4.5mg QD (3 caps QD)

Other:
• Placebo
Placebo timeline: Weeks 0-2: 20mg TID (1 cap TID)/1.5mg QD (1 cap QD) Weeks 2-4: 40mg TID (2 caps TID)/3.0mg QD (2 caps QD) Weeks 5-13: 60mg TID (3 caps TID)/4.5mg QD (3 caps QD)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Open Medicine Foundation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functional Capacity	Change in the total FUNCAP27 questionnaire score; The FUNCAP27 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
Primary	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
Primary	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
Primary	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	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.	15 weeks
Secondary	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.	15 weeks
Secondary	Daily Activity	Change in daily steps (steps/day) measured using Garmin Vivosmart 5	15 weeks
Secondary	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	15 weeks
Secondary	Blood Oxygen	Change in blood oxygen saturation (%) measured with Garmin VivoSmart 5	15 weeks
Secondary	Resting Heart Rate	Change in resting heart rate (bpm) using Garmin VivoSmart 5	15 weeks
Secondary	DANA Brain Vital-Simple Reaction Time (SRT)	Change in time (ms) required to recognize the presence of an object and tap the object	15 Weeks
Secondary	DANA Brain Vital-Procedural Reaction Time (PRT)	Change in time (ms) required to recognize 1 of 4 numbers and tap 1 of 2 buttons	15 weeks
Secondary	DANA Brain Vital-Memory Search (MS)	Change in time (ms) required to recognize letters that have previously been memorized	15 weeks