Clinical Research Directory

Taurine Supplementation in Adolescents With Post-COVID Condition

The COVID-19 pandemic has swept across the globe, affecting millions of individuals with varying degrees of severity. While many individuals recover from the acute phase of the infection, a significant proportion continue to experience persistent and debilitating symptoms long after the initial SARS-CoV-2 infection. This condition, known as Long COVID (LC) or sometimes referred to as Post-COVID Condition (PCC) or post-acute sequelae of COVID-19 (PASC), has emerged as a complex multisystemic condition and challenging public health issue. Contrary to initial perceptions, pediatric Long COVID is a significant health concern, with studies suggesting its prevalence ranges from 10% to 25% following infection. Research in the pediatric population has largely been limited to observational studies based on self-reported symptoms or large electronic healthcare datasets. The long-term outcomes and predictors of LC in children remain poorly described, highlighting an urgent need for further mechanistic research to characterize this complex condition. While acute COVID-19 symptoms are often milder in children relative to adults, some go on to develop a range of chronic physical, immunological, psychological, and neurological symptoms persisting for weeks to years after initial infection. The most commonly reported symptoms are similar to those seen in adults and include debilitating fatigue, respiratory distress, headaches, gastrointestinal symptoms, and neurocognitive impairment. Other frequently reported symptoms include muscle pain, sleep disturbances, olfactory and gustatory disturbances, exercise intolerance, and heart palpitations/cardiovascular symptoms. These symptoms can be new, or they may persist or fluctuate from the initial illness. Additionally, many children with LC experience psychological symptoms such as anxiety, depression, and mood disturbances, which are thought to be exacerbated by experiencing prolonged illness and subsequent lifestyle disruptions. Currently, effective treatments for LC remain elusive, leaving patients to contend with persistent symptoms that significantly impair their quality of life. For children and adolescents, these issues can profoundly impact their daily activities, academic performance, and social interactions/friendships. Symptoms like debilitating fatigue, cognitive impairment, and mood disturbances are especially disruptive by interfering with memory, energy levels, and overall development, often leading to school absenteeism, social withdrawal, and psychological distress. Therefore, it is imperative to explore novel therapeutic approaches that may alleviate the suffering of this patient population.

Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation

The goal of this clinical trial is to test whether a type of rapid outpatient brain stimulation that uses magnetic fields, called accelerated intermittent theta burst stimulation (iTBS), can treat symptoms such as brain fog, depression, and anxiety in patients with Long COVID. The main questions it aims to answer are: * Is iTBS effective and feasible for reducing Long COVID symptoms? We will measure these symptoms using the Symptom Burden Questionnaire. * Are there changes in inflammatory brain chemicals associated with treatment with iTBS? We will be looking at levels of choline in the brain, which is thought to be related to inflammation. Researchers will compare sham versus active forms of iTBS to see if the active group has greater improvement in symptoms. Participants will complete symptom surveys, cognitive tests, and magnetic resonance imaging scans at the beginning, middle, and end of treatment.

A Pilot rTMS Trial for Neuropsychiatric Symptoms of Long-COVID

This is a pilot randomized trial of rTMS for symptoms of fatigue and brain fog, and other neuropsychiatric symptoms of Long-COVID (Post-COVID, post-acute sequelae of COVID-19 infection, PASC). Twenty participants diagnosed with Long-COVID and recruited from the UCLA Long-COVID clinic will be randomized to receive active rTMS versus sham stimulation for 15 treatments followed by another 15 open-label rTMS treatments. Investigators will compare the safety and tolerability of rTMS vs Sham and examine within-group changes in symptoms of fatigue, sleep, pain, mood, and subjective and objective cognitive impairment. This project will provide information and pilot data for future larger clinical trials.

Longitudinal At Home Smell Testing to Detect Infection by SARS-CoV-2

The purpose of this study is to learn more about how to better track smell recovery in people who have been infected with the SARS-CoV-2 virus (which causes COVID-19). Many people who have been infected by this virus develop changes in their sense of smell (olfaction). We are interested in measuring smell function objectively via smell cards that test odor intensity, identification, and discrimination. Objective and precise olfactory testing that can be performed in the convenience of one's home will help identify people with smell loss after infection by SARS-CoV-2. We will use results from this test to better understand the relationship between SARS-CoV-2 infection and recovery of olfactory function and to learn whether the AROMHA longitudinal smell test is a reliable olfactory function tracking tool to quantify smell loss in the context of COVID infection. These results may inform the design of therapeutic clinical trials to accelerate the recovery of smell function.

Brain Stimulation in Long COVID

Cognitive problems and severe fatigue are two frequently occurring symptoms in long COVID, also known as Post-Covid Condition or Post-Acute Sequelae of COVID-19 (PASC), and their causes are currently unknown. Previous studies have shown reduced blood flow and increased inflammation in the brains of people with PASC. These brain processes are related to fatigue and cognitive problems. In other conditions, these disrupted brain processes have been treated safely and successfully with non-invasive brain stimulation. This may offer an effective treatment for people with PASC. The main goal of this clinical trial is to see whether non-invasive brain stimulation called repetitive transcranial magnetic stimulation (rTMS) can reduce fatigue in adults with PASC who also have trouble concentrating. rTMS uses short magnetic pulses on the scalp to gently stimulate a small brain area. In this study, 66 adults with PASC will be included, recruited through the Post-COVID Network Netherlands. Participants will be randomly assigned to receive either active rTMS or sham (placebo) rTMS. Sham rTMS feels and looks similar to the active treatment, but it does not generate effective magnetic pulses. The brain area that will be targeted is personalized using a brain scan (MRI) during a planning task. All participants will receive 24 rTMS sessions over six weeks (four per week). Fatigue will be measured within two weeks before and two weeks after treatment to determine whether active rTMS works better than sham. We will also look at cognition, brain connectivity and blood flow, signs of (neuro)inflammation, daily activity using an activity watch, and questionnaires about quality of life, mood, and sleep. Follow-up on cognition and questionnaires will take place 3 and 6 months after the end of the treatment.

Neural Mechanisms of Fatigue in Post-Acute Sequela of SARS-CoV-2

This proposal aims to understand the neurobiological mechanisms of fatigue in individuals with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). This knowledge will eventually provide candidate mechanisms to target with pharmacological intervention and inform rehabilitative care for those individuals suffering from symptoms of fatigue in PASC.

From Inflammation to Remodelling Towards Personalized Diagnosis in Post-acute Sequelae of COVID-19

Rationale: The diagnosis and pathogenesis of long COVID remains unknown. We have previously shown that \[68Ga\]FAPI Positron Emission Tomography-Computed Tomography (PET/CT) imaging shows potential for diagnosis and molecular understanding of this syndrome. We have previously shown that fibroblast activation protein (FAP) can be imaged in the lung, muscle and nasopharynx of long COVID patients (with dyspnea and fatigue). However, these preliminary data are derived from a selective group of patients with long COVID after critical COVID-19. We aim to explore the generalizability of these findings in patients with long COVID with dyspnea and fatigue, irrespective of the severity of their acute SARS-CoV-2 infection. Primary objective: To assess if pulmonary fibroblast activity, measured by \[68Ga\]FAPI-46 PET/CT, is higher in patients with current long COVID dyspnea and fatigue compared to patients with resolved complaints. Study design: This is a ZonMw funded single centre prospective observational cohort study of long COVID-19 patients with dyspnea and fatigue. Study population: We will recruit 60 adult long COVID patients (aged \>20 years) of which 30 have complaints of dyspnea and fatigue and compare them to 30 patients with resolved complaints and healthy controls. Main study parameters/endpoints: The primary endpoint is FAP expression in the lung measured by \[68Ga\]FAPI-46 PET/CT. Secondary endpoints are the expression of FAP in other tissues (muscle) and the relation between FAP and inflammation and remodelling biomarkers in various biological samples (e.g. serum/nasal epithelium). Study procedures: In a single visit day the following data and samples will be collected: questionnaires, a lung function test, 6-minute walking test, blood samples, nose swabs, \[68Ga\]FAPI PET/CT scan and HRCT scan. When increased \[68Ga\]FAPI uptake is measured in the muscles a muscle biopsy will be performed as well.

Physiological and QoL Benefits of Qi-Gong in Post-acute Sequelae of Covid-19

The goal of this clinical trial is to determine whether Qi-Gong can improve physiological function and quality of life (QoL) in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Study Objectives: To assess whether Qi-Gong improves physiological function in individuals with PASC. To evaluate whether Qi-Gong enhances quality of life in individuals with PASC. Study Design: If a comparison group is included, researchers will compare Qi-Gong with standard care to assess its effectiveness. Participant Involvement: Practice Qi-Gong three times per week for three months. Record physiological data monthly.