Clinical Research Directory

Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)

Background: SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from an acute COVID-19 infection may continue to have symptoms that persist for months or years. These can include neurological symptoms, such as headaches, loss of taste or smell, dizziness, or trouble walking. Pembrolizumab is a drug approved to treat certain cancers. Researchers think this drug might reduce long-term neurologic symptoms after a COVID-19 infection. Objective: To test pembrolizumab in people with ongoing neurologic symptoms of COVID-19. Eligibility: People aged 18 years or older who had COVID-19 at least 6 months ago and have ongoing neurologic symptoms. Design: Participants will have 7 clinic visits in 7 months. Participants will be screened. They will have a physical exam with blood tests. Swabs will be used to collect cells from inside the mouth and nose. They may opt to have an imaging scan. Participants will also have other tests before they are given the study drug. These include eye and skin exams; tests of their memory and thinking; and tests of involuntary body functions, such as heart rate, blood pressure, sweating, and digestion. Their grip strength and walking pace will be measured. They will wear a heart rate monitor for 24 hours. They will wear devices on a wrist and thigh to measure activity for 10 days. Participants will have a lumbar puncture (spinal tap): A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Pembrolizumab is given through a needle inserted into a vein. Participants will receive 1 dose of the drug. Participants will have 4 follow-up visits over 6 months. Tests may be repeated during these visits.

Use and Effectiveness of COVID-19 Vaccines Using State Vaccine Registries and Insurance Claims Data

This study aims to use vaccination information from state vaccine registries linked with HealthVerity insurance claims for the following: * to measure how effective the Pfizer-BioNTech vaccine is at preventing post-COVID conditions. * to understand characteristics of patients who are receiving COVID-19 vaccines. All patients whose information is kept unidentified in the HealthVerity database are eligible to be included for both aims of this study.

Exercise Training Using an App on Physical Cardiovascular Function Individuals With Post-covid-19 Syndrome

The aim of this study is to assess the effect of a physical exercise program via a mobile application on functional parameters in individuals with post-COVID-19 syndrome. This is a clinical trial involving 60 individuals with post-COVID syndrome who will be randomly assigned to either a control group (physical activity guideline) or an experimental group (app-based training).

Effect of 2-HOBA in Persistent Immune Activation in Long COVID POTS

Long COVID is defined by a range of symptoms affecting multiple organs that persist for more than three months following an acute SARS-CoV-2 infection. Approximately 7% of individuals who recover from SARS-Cov-2 infection develop Long COVID. Long COVID Postural Orthostatic Tachycardia Syndrome (LCPOTS) symptoms include fatigue, exercise intolerance, orthostatic intolerance, syncope, and heightened orthostatic tachycardia. Research has found that decreased parasympathetic activity in LCPOTS increases the production of highly immunogenic neoantigens Isolevuglandins (IsoLG-adducts). IsoLG-adducts induce formation of circulating monocyte/T cell complexes(doublets) leading to the persistent and unresolved immune response that continues after the initial infection. The purpose of the this research, is to study the effects of 2-hydroxybenzylamine (2-HOBA), an Iso-LG-adduct scavenger, its effects in immune markers and compare it with Placebo

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.

Second Prospective Cohort of Patients Entering the Multidisciplinary Care Pathway for Post-Covid Syndromes - SyPoCo2 Cohort

The study aims to identify clinical profiles of long-COVID patients and correlate them with immunological and molecular data in order to identify prognostic biomarkers and potential therapeutic targets.

Safety and Efficacy of Anakinra Treatment for Patients With Post Acute Covid Syndrome

The PRECISION is a proof-of-concept, phase II randomized clinical trial aiming to evaluate the efficacy and safety of anakinra in patients with Post-Acute COVID Syndrome (PACS) of the pro-inflammatory respiratory phenotype. Improvement is measured by a composite endpoint, namely, the "Score of PACS progression reversal"

Brain-Training Treatment for Long COVID in Older Adults

This research is being done to collect preliminary data on the potential of computerized "brain-training" exercises for treating Long COVID symptoms in older adults. The investigators hypothesize that computerized brain-training will be an acceptable and feasible intervention for treating Long COVID symptoms in older adults. The investigators also expect to provide initial evidence that computerized brain-training has potential for improving thinking, mood, and other aspects of everyday functioning in older adults with Long COVID.

Care for Veterans Post-COVID-19

The evidence-based Concordant Care approach involves engaging in processes that: 1) validate the patient's experience, 2) develop a shared understanding of the condition, and 3) create a patient-centered, whole health-oriented action plan to manage the condition. This is consistent with published expert opinion that Concordant Care underlies patients' (and clinicians') positive experiences of care for poorly understood conditions. Despite strong evidence supporting this care approach, there are no interventions to train clinicians on practices to provide Concordant Care for Veterans with poorly understood conditions such as Long-COVID. Part 1 of the study will optimize and test if a Concordant Care training improves VA clinicians' engagement in recommended practices to provide Concordant Care (i.e., validate, shared understanding, action plan) for Veterans with Long-COVID. This study will adapt and refine Concordant Care training for Long-COVID. Part 2 of this study will determine if Concordant Care training increases clinicians' engagement in recommended practices to provide Concordant Care and will explore the effectiveness of Concordant Care on care outcomes including satisfaction, adherence to care, \& disability for Veterans with Long-COVID. Veterans treated by clinicians receiving Concordant Care training will report their clinician more frequently engaged in recommended conversations (i.e., ask about Long-COVID, validate experience with Long-COVID, create a shared understanding and action plan), and Veterans will perceive greater shared understanding of Long-COVID with their clinicians than Veterans treated by clinicians in the control arm.

A Study of Positive Emotions With Long COVID-19

This study is testing a new brief mindfulness practice for people suffering from long COVID-19 symptoms. People suffering from long COVID are particularly vulnerable to negative emotions, as they must also cope with the long-term uncertainty of physical and psychological stress beyond the acute infection. The goal of the study is to measure the ability of a brief mindfulness practice to promote a sense of well-being in people suffering from long COVID.

Harnessing Optimism and Perseverance in the Face of Long COVID-Español

The Harnessing Optimism and Perseverance in the Face of Long COVID (HOPE-LC) program, created by Drs. Eric Watson and Amelia Hicks, is a group therapy model designed to foster resilience, adjustment, and coping skills for those living with chronic Long COVID. HOPE-LC\~Español provides a culturally and linguistically adapted version for Spanish-speaking individuals in Queens, developed with input from Spanish-speaking clinicians, Long COVID experts, and people with lived experience. Partnering with H+H/Elmhurst and H+H/Queens, the project aims to recruit 25 participants and evaluate program feasibility and preliminary efficacy.

IMPACT-D+: Immune-Modulating and Psychometric Effects of Accelerated TMS in Depression Plus Comorbid Post-COVID-19 Condition

This is a monocentric, randomized pilot study conducted at the Max Planck Institute of Psychiatry, Munich. The study investigates the effects of two different intermittent theta-burst stimulation (iTBS) schedules on biological and clinical outcomes in patients with depression and comorbid Post-COVID-19 condition (PCC). Participants will be randomized into two arms, both receiving a total of 30 active iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC) at 90% resting motor threshold using a PowerMAG 100 ppTMS stimulator: * Standard Arm: One iTBS session per day, five days per week, over six weeks. * Intensified Arm: Six iTBS sessions per day, approximately one-hour apart, over five consecutive days. The primary outcomes are changes in immunological blood markers (C-reactive protein \[CRP\], tumor necrosis factor \[TNF\], interleukin-1β \[IL-1β\], interleukin-6 \[IL-6\]) and depressive symptomatology measured by Beck Depression Inventory-II (BDI-II) and Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes include fatigue (Fatigue Severity Scale \[FSS\], Fatigue Scale for Motor and Cognitive Functions \[FSMC\], Post-Exertional Malaise questionnaire \[PEM\]), sleep quality (Pittsburgh Sleep Quality Index \[PSQI\]), daytime sleepiness (Epworth Sleepiness Scale \[ESS\]), functioning (Sheehan Disability Scale \[SDS\]), anxiety (Beck Anxiety Inventory \[BAI\]) and an exploratory adverse effect screening. Follow-up assessments will be performed three days after treatment completion and again at three months post-intervention to evaluate both short- and medium-term effects. Biospecimen collection will include approximately 141 ml of peripheral blood per participant across three time points (baseline, post-treatment, +3 days). Samples will be analyzed for inflammatory markers and securely stored in the institutional biobank of the Max Planck Institute of Psychiatry in accordance with data protection and ethical guidelines. Safety and tolerability will be continuously monitored, including documentation of adverse events. The results of this pilot study are expected to provide preliminary evidence on whether accelerated iTBS protocols may exert differential effects on neuroinflammatory processes and depressive symptomatology in patients with Post-COVID-19 condition, thereby informing larger controlled clinical trials.

Probiotic Use for Recovery Enhancement From Long COVID-19

The goal of this clinical trial is to learn if probiotics can improve symptoms and quality of life in participants with Long COVID.

Long-Covid-19 Alleviation Through Learning Mindfulness Study

This research is being done to study a mindfulness intervention among people who have symptoms of Post-Acute Sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID. Mindfulness is defined as paying attention to the present moment with non-judgment and acceptance. Here the investigators are studying whether a mindfulness intervention can help reduce stress, reduce Long COVID symptoms, and improve quality of life among people living with Long COVID. The mindfulness intervention is a series of recorded mindfulness sessions, which were created by the study team. People who decide to take part will be randomly assigned to receive the study mindfulness intervention immediately after joining the study or to receive the study mindfulness intervention 8 weeks after joining the study. All participants will continue their usual medical care. Participants will complete online surveys to measure symptoms over time. The study will last 6 months.

Cognitive Rehabilitation Therapy for COVID-19

Cognitive dysfunction, psychiatric symptoms, functional impairment, and disability following COVID-19 negatively impact Veterans' community functioning and quality of life, contribute to significant human suffering, and are costly to VHA. Rehabilitation is a critical priority for Veterans with long COVID. One promising treatment to improve functioning in Veterans with post-COVID-19 cognitive symptoms is Compensatory Cognitive Training (CCT). Previous studies have found that CCT is feasible, acceptable, and efficacious in Veteran populations with multiple sources of cognitive dysfunction. This randomized controlled trial aims to address important RR\&D priorities by examining feasibility, acceptability, and preliminary efficacy of a COVID-19-specific rehabilitation intervention, CCT for long COVID (CCT-C) compared to a robust control condition. The proposed study has the potential to improve cognitive function, functional independence, and quality of life for Veterans with late or delayed effects of secondary conditions related to COVID-19 infections.

Long COVID Brain Fog: Cognitive Rehabilitation Trial

This study will compare two approaches to cognitive rehabilitation in adults with long COVID with persistent, mild to moderate, cognitive impairment. One approach will feature (A) web-based computer "games" that trains how quickly individuals process information that they receive through their senses; (B) in-lab 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 (VNS), i.e., trans-auricular VNS (taVNS). Component B will include work-related tasks. This approach is termed Constraint-Induced Cognitive Therapy (CICT). The other approach will feature (A) web-based computer "games" that train reaction time and eye-hand coordination; (B) in-lab training on relaxation, healthy nutrition, and healthy sleep, (C) procedures designed to promote integration of these lifestyle changes into everyday life, and (D) taVNS. This approach is termed Brain Fitness Training (BFT). A subset of participants, who qualify for and and desire vocational rehabilitation (VR), will receive VR from the Alabama Department of Rehabilitation Services (ADRS) in addition to CICT or BFT. ADRS VR will include career counseling, prescription of on-the-job accommodations, and guidance on return-to-work. Those in the CICT + VR group will also receive on-the-job coaching from a peer mentor for a month after completing training. CICT, with or without VR, will involve 30 hours of training. Ten 3-hour in-lab, face-to-face, therapist-directed sessions will be scheduled. These sessions will feature one hour of gaming; the remainder will be committed to in-lab training on the target behaviors and the procedures designed to promote transfer of therapeutic gains to daily life and improving skills essential to work; the set of the latter procedures is termed the Transfer Package. ta-VNS will administered for 10 minutes before gaming and in-lab target behavior training. To accommodate the demands of participants' other activities, training sessions will be permitted to be scheduled as tightly as every weekday over 2 weeks or as loosely as every other weekday or so over 4 weeks. If a family caregiver is available, they will receive training on how to best support participants in their therapeutic program. After training ends, four follow-up phone calls will be scheduled approximately one-week apart with participants to promote integration of the skills gained during training into everyday life. BFT, with or without VR, will involve 30 hours of training following the same schedule as for CICT. Ten 3-hour in-lab, face-to-face, therapist-directed sessions will be scheduled. These sessions will feature one hour of gaming; the remainder will be committed to in-lab training on the target behaviors (healthy sleep, nutrition and relaxation habits) and the procedures designed to promote transfer of behavior change to daily life. ta-VNS will be administered for 10 minutes before gaming and in-lab target behavior training. If a family caregiver is available, they will receive training on how to best support participants in their therapeutic program. After training ends, four follow-up phone calls will be scheduled approximately one-week apart with participants to promote integration of the skills gained during training into everyday life. Participants will be randomly assigned to the interventions. Randomization will be stratified by whether participants qualify for and desire VR from ADRS or not. If yes, participants will be randomized in equal numbers to CICT + VR or BFT + VR. If no, participants will be randomized in equal numbers to CICT or BFT. Testing will happen one month before treatment, one day before treatment, one day afterwards, and 6-months afterwards. 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. Another important outcome measure will be whether or not participants were able to return back to work or had significant improvements in their work activities.

Microbial and Cytokine Signatures in Long COVID Patients

We aim at identifying potential biomarkers in plasma indicative of post-acute coronavirus SARS-CoV-2 Syndrome (Long COVID). Our case-control study will compare Long COVID patients to healthy patients from Sutter Health.

Dietary Intervention to Mitigate Post-Acute COVID-19 Syndrome

The primary objective of this study is to conduct a 16-week randomized controlled trial aimed at investigating the effectiveness of the Whole-Diet Approach when following a healthy US-style diet rich in anti-inflammatory properties. The study will focus on evaluating its impact on reducing symptoms related to Post-Acute Sequelae of SARS-CoV-2 Infection (PACS) in adults aged 50 years and older. The main research questions this study aims to answer are: 1. Does adhering to a healthy US-style diet, which is abundant in anti-inflammatory properties, effectively mitigate fatigue symptoms in adults with PACS? 2. Does adhering to a healthy US-style diet, which is abundant in anti-inflammatory properties, effectively mitigate declines in muscle function and physical performance in adults with PACS? At the beginning of the study, eligible participants will be randomly assigned to either the Dietary Intervention Group, where they will receive personalized dietary plans and weekly sessions, or the Attention Control Group, where they will attend general health sessions on a weekly basis as well. This research intends to shed light on the potential benefits of the Whole-Diet Approach and its role in ameliorating PACS-related symptoms among older adults. By comparing the outcomes of the two groups, we hope to gain valuable insights into the effectiveness of this dietary intervention in improving the quality of life for individuals dealing with PACS.

Attention, Memory and Quality of Life in Post-COVID-19 Adults

The pandemic has highlighted social, economic, educational, and political issues that have affected the health and quality of life of millions of Brazilians. Currently, attention and memory impairment remains predominant among the cognitive symptoms of Coronavirus observed in adults. The persistance of the reffered impairment after 12 weeks of COVID-19 is known as cognitive impairment in post-COVID-19 syndrome. Despite studies indicating the negative effects of COVID-19 on attention and memory, there is a gap in the literature regarding its effects on self-reflection and insight. Previous studies highlight the role of self-awareness as an essential cognitive process that aids the criation of a resolution for the social consequences of the ongoing pandemic. Thus, understanding the relationship between self-reflection, insight, memory, and quality of life in adults that presented COVID-19 could reveal how memory loss might affect the ability to evaluate and understand one's own behaviors and quality of life. Moreover, this study could provide a background for future interventions to enhance attention, memory, self-reflection, and insight in this population. In this context, quantitative electroencephalogram neurofeedback training (EEGq-NFT) is a promising non-invasive intervention designed to improve cognition, such as attention and working memory. By modifying electrophysiological patterns in the cerebral cortex. Considering the information presented, the question is what is the relationship between cognitive failures, self-reflection and insight, and quality of life in adults who had COVID-19, and what is the efficacy of EEGq-NFT training in rehabilitating attention and working memory in adults with cognitive impairment due to post-COVID-19 syndrome. This study aims to examine the relationship between cognitive failures, self-reflection, insight, and quality of life in adults post-COVID-19, as well as to assess the efficacy of EEGq-NFT in improving attention and working memory in adults with cognitive impairment due to post-COVID-19 syndrome. Method 1 will employ a survey with cross-sectional design and quantitative data analysis. A total of 385 adults will be recruted. Data will be collected through online forms. Cognitive Failures Questionnaire, Self-Reflection and Insight Scale and WHOQOL-bref scale will be used. In Method 2, a quasi-experimental with quantitative data analysis will be employed. A total of 60 participants will be randomly assigned to an EEGq neurofeedback training group (n = 20), an active control group called SHAM EEGq-neurofeedback (n = 20), and a waiting list control group (n = 20). The theta/beta ratio reduction protocol at Cz will be used, with 10 sessions of 30 minutes each. The Psychological Battery of Attention 2 (BPA-2) and Digit Span Test will be employed to measure attention and working memory levels. Statistical analyses will be performed using IBM SPSS version 25 with statistical significance set at p \< 0.05 for a 95% confidence interval. The research follows all ethical standards for studies involving human subjects and was submitted for review and approval at the Research Ethics Committee. A understanding of memory levels, self-reflection, insight, and quality of life in adults post- COVID-19 is expected as a result of the present study. Additionally, this study expects that EEGq-NFT will be effective in reducing the theta/beta ratio, as well as improving attention and working memory in adults with cognitive impairment in post-COVID-19 syndrome.

A Study of Apabetalone in Subjects With Long -COVID

This is an open label, multicentre, phase II clinical trial that aims to assess the efficacy and safety of oral Apabetalone with background dapagliflozin for up to 12 weeks in T2DM patients with a history of probable or confirmed SARS-CoV-2 infection, with symptoms within 3 months from the onset of COVID-19 that last for at least 2 months and cannot be explained by an alternative diagnosis.

Sodium Citrate in Smell Retraining for People With Post-COVID-19 Olfactory Dysfunction

The goal of this pilot study is to assess the feasibility and impact of using sodium citrate nasal spray as an adjunct to olfactory retraining in participants with long-term post-COVID-19 olfactory dysfunction. The main questions it aims to answer are: * Is sodium citrate nasal spray in addition to smell retraining feasible for participants to use in terms of participant need/desire, adherence, and adverse events? * Does sodium citrate nasal spray in addition to smell retraining further improve smell as compared to normal saline spray and smell retraining? Participants will: * Provide consent for enrollment. * Undergo smell testing via Sniffin' Sticks. * Use a nasal spray (either sodium citrate or normal saline) followed by olfactory retraining twice a day for 12 weeks. * Return for follow-up Sniffin' Sticks testing. Researchers will compare the sodium citrate group and the normal saline group to determine differences in smell improvement.

Incidence, Associated Factors, and Burden of Post COVID-19 Condition in Brazil

This is a national retrospective cohort study with internet-based recruitment which intends to enroll 1,694 adult patients with COVID-19 diagnosis during the SARS-CoV-2 omicron wave in Brazil. Participants with confirmed symptomatic COVID-19 after january 2022 will be evaluated in order to assess incidence, potential risk factors and impact of post COVID-19 condition according to the WHO definition on health-related quality of life and other relevant patient-centered outcomes.

Dysfunctional Breathing in Post COVID-19 Condition.

The goal of this observational study with a cross-sectional design is to investigate what signs, symptoms and assessment which can describe and explain dysfunctional breathing in patients with post COVID-19 condition. The main question aims to answer which measurements can identify and asses dysfunctional breathing in patients with post COVID-19 condition? Participants for this study will be recruited from the ReCov cohort will be evaluated with diffrent measurments and questionnaires.

Effects of Individual Tailored Physical Exercise in Patients With POTS After COVID-19 - a Randomized Controlled Study

Covid-19 has the potential to affect physical, cognitive and psychological functions in multiple ways. It has been clear that a significant proportion of patients with Covid-19 develop long-term symptoms. The term post COVID-19 condition (defined by WHO) is used to describe the wide range of prolonged symptoms following the infection. Patients may need specialized rehabilitation to be able to meet the complex symptoms and problems that may arise. A more specific syndrome that seems to occur more frequently than expected in the group of non-hospitalized patients with post COVID-19 condition is the postural orthostatic tachycardia syndrome (POTS). A randomized controlled design will be used to evaluate the effects of individual tailored physical exercise in patients with POTS after Covid-19. Participants: Adults (\>18 years) with post COVID-19 condition and diagnosed with POTS (n=60) will be included. Exclusion criteria: known pregnancy, cancer, already ongoing individual physical exercise (specific for POTS), or not able to perform measurements and/or intervention. Procedure and outcomes: The primary outcomes are objectively measured time in upright position and health-related quality of life. Secondary outcomes are: physical activity, physical capacity, work ability and disease specific symptoms measured with tests and questionnaires. Prior to randomization baseline measurements will be performed, aswell as after 16 weeks, 6 months and 12 months. Intervention: Participants randomized to intervention will receive standard care and undergo a individually designed physical exercise program during 16 weeks, supervised and guided by a physiotherapist. The intervention will consist of different exercises to enhance muscle strength and endurance. Progression will be according to a program (based on previous feasibility studie) but should be halted if post exertional malaise (PEM) or other problems occur. Controls: Participants randomized to control will receive standard care during 16 weeks. Measurements of both groups (control and intervention) will be repeated after completion of a period of 16 weeks.