Clinical Research Directory

RECOVER-ENERGIZE Platform Protocol_Appendix A (Exercise Intolerance)

This is a platform protocol designed to be flexible so that it is suitable for a range of interventions and settings within diverse health care systems and community settings with incorporation into clinical COVID-19 management programs and treatment plans if results achieve key study outcomes. This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating interventions to address and improve exercise intolerance and post-exertional malaise (PEM) as manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The focus of this protocol is to assess interventions that can improve exercise capacity, daily activities tolerance, and quality of life in patients with PASC.

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.

LOng COvid COmorbidities: Andrological, Reproductive, Sexual Dysfunctions in Patients Recovered From COVID-19

Considering the compelling amount of studies focused on patients in the active phase of COVID-19 disease and the scarcity of studies focused on patient cured from disease aimed at evaluating the sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the purpose of the study is to investigate, in patients recovered from COVID-19 disease: 1) whether SARS-CoV-2 infection has induced in male patients, a primary (testicular) and / or secondary (pituitary) damage to the hypothalamic-pituitary-testicular hormonal axis, structural and / or functional damage to the testis and penis, sexual dysfunction or fertility disorders; 2) the prevalence in male and female patients of chemosensory symptoms (olfactory dysfunction) and assess whether there is a correlation between the prevalence, severity, duration and eventual persistence of olfactory dysfunction and the severity of COVID-19 disease. Patients will be evaluated at baseline (at discharge from infectious and/or pneumology unit) and after 3- 12 months. A better definition of the prevalence and type of sequelae after recovery from COVID-19 disease could significantly improve the therapeutic management and long-term follow-up of these patients, with a relevant impact in terms of health resources and public health.

LOng COvid COmorbidities: Endocrine,Metabolic,Neuropsychiatric,Muscle,Cardiovascular,Pulmonary,Dermatologic Dysfunctions

Considering the compelling amount of studies focused on patients in the active phase of COVID-19 disease and the scarcity of studies focused on patient cured from disease aimed at evaluating the sequelae of SARS-CoV-2 infection, the purpose of the study is to investigate whether in patients recovered from COVID-19 disease, SARS-CoV-2 infection has induced: 1) endocrine-metabolic function damage; 2) neuro-psychiatric damage; 3) muscle damage; 4) pulmonary damage; 5) cardiological damage; 6) venous vascular damage; 7) dermatological damage. Patients will be evaluated at baseline (at discharge from infectious and/or pneumology unit) and after 3- 12 months. A better definition of the prevalence and type of sequelae after recovery from COVID-19 disease could significantly improve the therapeutic management and long-term follow-up of these patients, with a relevant impact in terms of health resources and public health.

Telerehabilitation Decision Support System: Pilot Testing Protocol

This study follows the successfully completed HOLOBalance project which was funded by the EU Horizon 2020 scheme. TheHOLOBalance platform delivers exercises demonstrated via a hologram of the physiotherapist and corrected in real time by the hologram prompts based on performance monitoring via sensors. Further information is available at: https://holobalance.eu/. HOLOBalance was developed as a comprehensive rehabilitation protocol for individualised remote (tele)rehabilitation balance physiotherapy programme. It includes different multisensory balance and gait exercises, physical activity and memory training and exergames (video games which are also exercises) to improve balance function in older adults. The system can thus assess and remotely monitor how users are performing the exercises. This pilot testing of a multisite randomised control trial (TeleRehab DSS, short for TeleRehabilitation Decision Support System) aims to investigating the usability and feasibility among a smaller sample population at each clinical site, identifying any technical bugs, and/or clinical procedural flaws to be remedied before delivery of the full-scale RCT.

RECOVER-AUTONOMIC: Platform Protocol, Appendix A (IVIG)

This study is a platform protocol designed to be flexible so that it is suitable for a wide range of settings within health care systems and in community settings where it can be integrated into COVID-19 programs and subsequent treatment plans. This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating various interventions for use in the treatment of autonomic dysfunction symptoms, including cardiovascular complications and postural orthostatic tachycardia syndrome (POTS), in Post-Acute Sequelae of SARS-CoV-2 infection (PASC) participants. The interventions tested will include non-pharmacologic care and pharmacologic therapies with study drugs.

Effectiveness and Acceptability of the Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders in People With Long COVID-19.

This Randomized Controlled Trial (RCT) aims to assess the effectiveness and acceptability of the Unified Protocol (UP) in an online group format for the treatment of emotional disorders in adults. Participants will be 90 adults (45 in the control group and 45 in the experimental group) with diagnosis of long COVID and comorbid emotional disorders. Participants will be recruited at Hospital Royo Villanova from Zaragoza, Spain. In this study it will be explored whether the changes obtained after the intervention in emotional disorders and cognitive complaints are maintained over 12 months. Additionally, levels of chronic stress will be longitudinally evaluated in the experimental group through accumulated cortisol levels in hair, before and after the application of the UP.

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.

NENCA Study on Neurological Complications of Long COVID-19 in Children and Adolescents; Neurophysiological, Electroencephalographic and Neuroradiological Investigation

The study seeks to investigate the neurological effects caused by Covid-19 in children and adolescents in the 6-16 age group. To do this, neuropsychological scales, an EEG and an MRI were used.

Register Study: Implementation of Pharyngeal Electrostimulation Therapy for the Treatment of Acute Neurogenic Dysphagia

Neurogenic dysphagia occurs with disruption of neurological systems or processes involved in the execution of coordinated and safe swallowing. It is common in patients with neurological diseases, in particular in patients treated in Intensive Care Units (ICU) who are intubated (up to 62%) and / or tracheotomised (up to 83%). Dysphagia is one of the most common and most dangerous symptoms of many neurological diseases. In addition, neurogenic dysphagia can have a significant impact on quality of life, medication efficacy, and malnutrition. Dysphagia is currently treated conservatively on evidence-based exercises, individually adapted to each patient. In the recent years pharyngeal electrostimulation has been established and shown a positive impact on outcome. In fact, this type of therapy has not only become an addition to the existing therapy, but an important alternative for patients difficult to treat by other means. The Phagenyx® is a medical device, which has lately been used more frequently in multiple hospitals for treatment of neurogenic dysphagia. For nearly two decades pharyngeal electrostimulation has been further developed and optimised. This therapy initiates changes in the swallowing motor cortex through neuroplasticity as well as local changes in peripheral sensory architecture associated with swallowing. Bath and colleagues (2020) recently reported the efficacy of pharyngeal electrostimulation (Phagenyx®) in various neurological conditions. As a result, of current published studies, the use of pharyngeal electrostimulation probe, in selected patients, with neurological diseases with moderate to severe neurogenic dysphagia will be evaluated. This trial will initially start as quality assurance project with the aim to extent it into a monocentric based register study. The Investigators aim to validate the effectiveness of pharyngeal electrostimulation for the treatment of moderate to severe neurogenic dysphagia by systematically recording specific dysphagia-relevant parameters. At present, it is still uncertain to what extent patients with neurogenic dysphagia in the context of a non-acute neurological disease could benefit from this method. The research questions: Does the use of the pharyngeal electrostimulation probe have an influence on the outcome of dysphagia in patients with moderate to severe neurogenic dysphagia? How long after therapy, can the use of the pharyngeal electrostimulation probe lead to oral food intake and/or removal of a tracheal cannula?