Clinical Research Directory

Patient-Centered Assessment of Symptoms and Outcomes

Background: The cause of fatigue is not well understood. It can be felt differently by different people. Some people think there are different types of fatigue, with different causes. Researchers think a therapy to treat one type of fatigue in one condition should be able to treat that type of fatigue in other conditions. Objective: To understand the types of fatigue. Eligibility: Adults 18 and older who have felt fatigue for more than a month, and non-fatigued adults Design: Participants will be screened with a physical exam, their medical history, a vision test, and blood and urine tests. Participants will begin to track the foods they eat. This study will involve up to 10 visits. Each visit will last no more than 4 hours. In Stage 1, participants will have an interview, fill out questionnaires, and play computer games. They will take walking and handgrip tests. They will give blood, urine, and saliva samples. They will wear a wrist monitor at home for 7 days and write down their activities. They will be put into a group: fatigue or non-fatigued control. In Stage 2, participants will answer questionnaires and give a blood sample. They will have heart tests. They may take exercise and lung function tests that include wearing a nose clip. They may have an optional brain MRI: They may wear an electrode cap on their head during the scan to measure brain activity. They will lie on table that slides into a cylinder. They may perform tasks in the scanner. After the study, participants might be contacted about other studies.

Hyperbaric Oxygen Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

This study evaluates the effects of hyperbaric oxygen therapy (HBOT) in patients with mild to moderate CFS/ME. Participants will undergo 60 HBOT sessions over 3 months with a 3-month follow-up, including physical, cognitive, imaging, and laboratory assessments.

ME/CFS Brain Fog: Cognitive Rehabilitation Trial

The purpose of this study is to compare two approaches to cognitive rehabilitation in adults with post-viral cognitive syndrome, which resulted in brain fog. All participants will be screened for eligibility prior to participation. Most of the procedures will take place over a phone call or secure telehealth platform (i.e., Zoom). However, participants will be asked to visit UAB on three occasions for blood sample collection and brain imaging (about 2 hours each). Online testing will happen one month before treatment, one day before treatment, one day afterwards, and 6 months afterwards. The study will utilize two different forms of rehabilitation training to improve participants' cognitive ability. Participants will be randomized to one of the two treatment groups. The first treatment approach, known as Constraint-Induced Cognitive Therapy (CICT), will feature (A) web-based computer "games" that trains how quickly individuals process information that they receive through their senses; (B) online training on everyday activities with important cognitive components, (C) procedures designed to transfer improvements in cognition from the treatment setting to everyday life, and (D) a non-invasive form of vagus nerve stimulation, also known as trans-auricular VNS (taVNS). The second approach, known as Brain Fitness Training (BFT), will include (A) web-based computer "games" that train reaction time and eye-hand coordination; (B) in-lab training on relaxation, breathing, healthy nutrition, and healthy sleep, (C) education about how relaxation, breathing, nutrition, and sleep are connected to thinking effectiveness, and (D) taVNS. Approximately 30 hours of training will be conducted over a secure telehealth platform (i.e., Zoom) in the span of two- to four- weeks. A typical CICT session will consist of one hour of gaming, with the bulk of the session being spent on cognitive training of the target behaviors and procedures designed to promote transfer of therapeutic gains to daily life. ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. A typical BFT session will consist of one hour of gaming, training on healthy lifestyle behaviors (i.e., healthy sleep, nutrition, and relaxation habits), as well as procedures designed to promote transfer of behavior changes to daily life. Ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. Training sessions in both conditions will be scheduled based on participants' availability, with the options for sessions scheduled to be as close as every weekday over 2 weeks or as loosely as every other weekday (i.e., over a 4-week span). If a caregiver is available, they will receive training on how to best support participants in their therapeutic program. After the training ends, both groups will receive 4 follow-up phone calls approximately one week apart to promote integration of the gained skills into everyday life. Outcomes measured will include cognitive processing speed, cognitive function on laboratory tests, and spontaneous performance of everyday activities with important cognitive components in daily life.

Unhide® Project: A Digital Health Platform to Collect Lifestyle Data for Brain Inflammation Research

The unhide® Project is a non-interventional, longitudinal research study designed to establish a secure data repository of demographic, health, and lifestyle information from individuals with brain inflammation and related neuroinflammatory conditions. Participants in the United States aged 2 years and older will provide self-reported health data, biometrics, and symptom diaries through the MyDataHelps™ app (branded as unhide® for this study). The goal is to create comprehensive longitudinal profiles to facilitate research into disease subtypes, causes, diagnostics, and potential treatments, as well as to identify potential participants for future optional studies. "Healthy" individuals without brain inflammation are also eligible to participate. The digital health research platform used in this study was originally developed and designed by Solve M.E and was called SolveTogether. The Brain Inflammation Collaborative (BIC) expanded upon Solve M.E.'s work to include related diagnoses, pediatric participants, enhance symptom tracking, and more. BIC and Solve M.E. combined Solve Together and unhide®, to create The unhide® Solve Together Unified Platform in 2025.

OutreAch MediCal Care for HousEbound Patients With Post-COVID-19 Syndrome or ME/CFS of Any Cause (ACCESS)

The significance of the Post-COVID Syndrome (PCS) has been widely acknowledged. Various efforts are made to find out about the pathomechanisms behind PCS and to establish therapies. One sub-group of PCS-patients, however, is generally excluded from any studies, and that are those who are unable to visit outpatient clinics or hospitals for diagnostic work up or participation in clinical trials, as they are unable to leave their home and to seek medical support on their own physical and mental capabilities. They are housebound, mostly or totally bedridden. Similar cases are known from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) of any cause and are graded as moderate to very severe ME/CFS according to the Canadian Consensus criteria. The patients are usually seen by their family doctor and have no access to medical specialists. The planned project aims to find out about the prevalence of this most severe manifestation of PCS, the clinical characteristics, the prevalence of mimics, risk factors and impact of the disease on the patients' life and their family/caregivers. Individual care and treatment plans will be developed and the effect of monthly consultation hours for patients and caregivers upon the patients' health status and the caregiver burden will be evaluated in a randomized controlled trial. The project will be performed in close cooperation between patients, caregivers, the patient's family doctor and a board of experts from internal medicine, neurology, psychosomatic medicine and general medicine at Hannover Medical School. We expect an improvement of the patients' and caregivers wellbeing with intensified medical care. We are aware, however, that intensification of the patient-doctor interaction carries the risk to exacerbate the patients' symptoms. The results of our study will show how current models of care for PCS and ME/CFS patients should be modified to fit to the individual patient's aims and capacities.

LIFT: Life Improvement Trial

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.

Vagus Nerve Stimulation to the Ear to Improve Symptoms in Post-COVID-19 and ME/CFS

This study is testing whether a gentle electrical stimulation of a nerve in the ear, called the vagus nerve, can help reduce fatigue and improve symptoms in people with Post-COVID Syndrome or Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The treatment, known as transcutaneous auricular vagus nerve stimulation (taVNS), is non-invasive and can be done at home using a small device. Participants will try two different types of stimulation, called Intervention A and Intervention B, to see which may be more effective. Each intervention lasts 4 weeks and will be separated by a break of at least 4 weeks. Participants will use the device at home twice a day for 30 minutes. Fatigue, quality of life, sleep, and daily activity will be tracked through surveys and wearable devices. All parts of the study-including check-ins and data collection-will be done remotely. The goal is to learn whether this type of at-home nerve stimulation can safely improve symptoms in people with Post-COVID Syndrome or ME/CFS.

The Use of Directed Probiotics in ME/CFS: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

This clinical study aims to evaluate the use of i3.1 probiotic in participants who meet the Institute of Medicine (Canadian Consensus Criteria) case definition for ME/CFS and who may or may not be diagnosed with irritable bowel syndrome (IBS). The main questions it aims to answer are: * how effective is the usage of the i3.1 probiotic to reduce gastrointestinal (GI) inflammation and normalize the GI and systemic/brain interface? * how well is it working on IBS severity? The study sample is 100 male and female participants aged 45 to 70 years with ME/CFS (per the Canadian Consensus Criteria); one-half of the participants will have co-morbid IBS (per Rome IV criteria). Participants will receive an i3.1 or a placebo and be assessed at baseline, at eight weeks, and at 12 weeks (four weeks post-treatment completion).

Multi-Center Registry for ME/CFS

The ME/CFS study (MECFS-R) aims to create a large-scale registry that provides data on epidemiology, phenotypes, and disease trajectories of and health care for ME/CFS at any age in Germany, which can be used for future clinical trials.

Skeletal Muscle in PASC and ME/CFS Patients

Rationale: A common feature in patients with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) and Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are skeletal muscle-related symptoms, such as muscle pain, weakness, fatigue and post-exertional malaise. Objective: The primary aim is to determine markers for skeletal muscle structure and function, and circulating factors, in patients with PASC and ME/CFS, and compare with controls. The secondary objective is to determine skeletal muscle structure and function before and after induction of post-exertional malaise, and assess the relationships between the measures obtained from muscle biopsies and parameters of exercise tolerance. Study design: Case-control observational study Study population: Patients with PASC, ME/CFS and healthy human volunteers, 18 - 65 yr old. Intervention (if applicable): none Main study parameters/endpoints: Primary outcome parameters are markers for local inflammation, viral infiltration, mitochondrial respiratory function and myokine concentrations in a muscle biopsy and venous blood before and after induction of post-exertional malaise. Heart rate variability and measures of exercise performance will also be determined. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will be asked to perform physical exercise tests, give muscle biopsies (2 samples), and various blood samples. There is some extent of burden and risk associated with harvesting muscle biopsies and blood samples, however this will be mitigated by the fact that these procedures will only be carried out by trained physicians. Moreover, the scientific gain from obtaining intracellular information outweighs these relatively quick procedures with minimal discomfort afterwards. The acute risks of the physical exercise measurements are negligible. The main risk for patients is that these patients often suffer from post-exertional malaise, which causes the participants to feel fatigued for some time after the maximal exercise test. It is one of the aims to better understand post-exertional malaise.