Clinical Research Directory

A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults

This phase 1 randomized, open-label, dose-escalation clinical trial evaluates the safety and immunogenicity of OCU500, a ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine, in healthy adults aged 18-64 who previously completed a primary COVID-19 vaccination series and at least one booster. The study evaluates two dose levels (1×10\^10 viral particles (VP) and 5×10\^10 VP) and two routes of administration (intranasal and inhaled). The trial includes 80 participants across four study arms (20 per arm). The primary objective is to evaluate the safety and reactogenicity of a single dose of OCU500 administered in previously vaccinated healthy adults.

Longitudinal Deep Phenotyping of Central Mechanisms in Dysosmia: A Pilot Study Using Electrobulbogram (EBG), Functional MRI (fMRI), and Diffusion-Weighted Imaging (DWI)

Background: Loss of the sense of smell can seriously affect a person's quality of life. The ability to smell can be damaged by many factors, including illnesses, injuries, and exposure to toxic chemicals. The effects can vary, including complete loss of smell, partial loss, and parosomia, which is when things smell differently than they should. Objective: To study how brain function changes in people with different types of smell disorders. Also, to look at how smell loss affects quality of life over time. Eligibility: People aged 18 years or older with a disorder that affects their sense of smell. Healthy volunteers are also needed. Design: Participants will have 5 study visits over 1 year. They will have various tests and procedures: Smell tests. They will have several tests that involve smelling different items and answering questions. Questionnaires. They will answer questions about their health, mood, sense of smell, and daily habits. Magnetic resonance imaging (MRI) scans. They will lie on a bed that slides into a tube. Padding will hold their head still. They will smell different odors while in the scanner. Electrobulbogram (EBG). They will wear a soft cap with sensors that measure brain activity. They will smell different odors while wearing the cap. Nasal endoscopy. A flexible tube will be inserted into a nostril to view the inside of the nose. Biopsy. A numbing substance will be sprayed into the nose. Then a scissor-like tool will be used to collect a sample of tissue from one or both nasal passages. Samples of blood, urine, and nasal fluid will be taken.

A Longitudinal Study of COVID-19 Sequelae and Immunity

Background: COVID-19 is a disease caused by the SARS-CoV-2 virus. It infects the respiratory tract. Some people who get COVID-19 have only mild symptoms. But for others, infection leads to pneumonia, respiratory failure, and, in some cases, death. Researchers want to learn more about any effects that may persist after people recover from COVID-19. Objective: To learn about any long-term medical problems that people who have recovered from COVID-19 might have, and whether they develop an immune response to SARS-CoV-2 that provides protection against reinfection. Eligibility: People age 18 and older who have recovered from documented COVID-19 or were in close contact with someone who had COVID-19 but did not get the infection Design: Participants will be screened over 2 visits. During visit 1, they will answer questions about any symptoms they are having and will be tested for SARS-CoV-2 infection which will involve a nasal swab sample or other FDA approved test. If the test is negative, they will proceed to the second visit, which will include: Physical examination Medical history Mental health interview (which may be recorded if the participant agrees) Chest x-ray (for recovered COVID-19 participants only) Blood and urine tests Pregnancy test (if needed) Lung function test (for recovered COVID-19 participants only) 6-minute walk test (for recovered COVID-19 participants only) Questionnaires about their general and mental health Leukapheresis to collect white blood cells (optional). Participants will be put into 1 of 2 groups: the COVID-19 group or the close contact group. Participants will have study visits every 6 months for 3 years. They will repeat some of the screening tests. Participants in the COVID-19 group may have visits more often if they develop symptoms that suggest re-infection with SARS-CoV-2....

Effectiveness of An Influenza/COVID-19 Vaccine (mCombriax [mRNA-1083]) in Adults ≥ 65 Years

The purpose of this pragmatic randomized trials is to evaluate the comparative vaccine effectiveness (cVE) of mCombriax® (mRNA-1083) versus same day co-administration of the active comparators (i.e., high-dose influenza vaccine/Efluelda® and mRNA-1273/Spikevax®) among adults aged 65 years and older.

Dime La VerDAD: Verify, Debunk, and Disseminate

Dime la Verdad (Tell me the truth) will evaluate the use of storytelling by community health workers as a communication strategy to disseminate reliable health information on social media and encourage informed decision-making in favor of recommended immunizations in communities with high morbidity and mortality due to respiratory virus infections. Dime La Verdad is an innovative social media capacity-building program based on theoretical frameworks related to health communication that empowers community health workers to disseminate reliable information about respiratory virus protection strategies through the use of personal narratives on social media. The proposed work will use a rigorous stepped wedge design to 1) deliver a scalable program of science communicators using an adapted curriculum grounded in principles of health communication, 2) evaluate how diffusion of health messaging is perceived on social media, and 3) discern how use of personal narratives to enhance science communication can encourage informed decision-making to promote evidence-based immunization practices and improve health outcomes.

Evaluation of Safety, Tolerance, and Efficacy of Allogeneic LB-DTK-COV19 in Severe Coronavirus Disease 2019 Patients

The goal of this clinical trial is to evaluate the safety, tolerability, and efficacy of allogeneic SARS-CoV-2-Specific T cells (LB-DTK-COV19) in patients with persistent clinical symptoms following a positive SARS-CoV-2 PCR test for 14 days or longer. The main questions it aims to answer are: * What is the maximum tolerated dose of LB-DTK-COV19 based on dose-limiting toxicity? * What treatment emergent adverse events occur following LB-DTK-COV19 infusion? * Does LB-DTK-COV19 result in clinically significant improvement or worsening of clinical symptoms following infusion? Participants will: * Receive a single intravenous infusion of LB-DTK-COV19 (low dose: 5x10\^6/m\^2; mid dose:1x10\^7/m\^2; high dose: 2x10\^7/m\^2). * Attend follow-up visits at the clinic for 6 months after the infusion.

Examining How a Facilitated Self-Sampling Intervention and Testing Navigation Intervention Influences COVID-19 Testing

Antigen self-testing kits are more available at this stage in the pandemic, but among vulnerable populations, use is still low and instructions for antigen testing are not typically designed for low health literacy populations. Studies are needed to explore access and use of antigen tests among vulnerable populations and examine if low-health-literacy-designed interventions improve COVID-19 testing decisions and behaviors. This study will focus on understanding factors associated with rapid COVID-19 testing, specifically. The primary objectives of the embedded study are to 1) Determine the effectiveness of community-level intervention using door-to-door recruitment and education in increasing COVID-19 testing and 2) Compare the effectiveness of the CHW- Facilitated Self-Sampling Intervention (FSSI) vs. CHW Testing Navigation Intervention (TNI).

Prospective Natural History Study of Smoking, Immune Cell Profiles, Epigenetics and COVID-19

Background: Early evidence in the COVID-19 pandemic suggests that smokers are at a higher risk of having severe effects or dying from the disease. Smoking causes changes in immune cells. Researchers think this may be the reason why smokers are more likely to have severe effects from COVID-19. Researchers want to better understand the interaction between smoking history, the immune system, and COVID-19. Objective: To better understand how COVID-19 affects smokers and non-smokers immune systems before and after being infected with the virus. Eligibility: Healthy people ages 30-55 who are a smokers or non-smokers who may potentially contract COVID-19 Design: Participants will be screened over the phone. They will answer questions about their demographics, medical history, medications, and smoking status. Participants will have up to 6 monthly visits. At the first visit, participants will have blood tests. Blood will be drawn through a needle in an arm vein. They will provide a saliva sample in a container and have a cheek swab. The participant will also have a nasal swab to see if they currently have COVID-19. Their height and weight will be taken. They will complete questionnaires about their medical history and smoking status. Participants will then have monthly visits. They will have blood draws to test for COVID-19 antibodies. They will provide a saliva sample in a container and have a cheek swab. The participant will also have a nasal swab to see if they currently have COVID-19. These visits will occur 4 times or until they have a positive antibody result. Participants will have a final visit. They will have blood tests. They will provide a saliva sample in a container and have a cheek swab. The participant will also have a nasal swab to see if they currently have COVID-19. If at any time participants test positive for a COVID-19, they will be rescheduled 14 days or more after they no longer have symptoms....

Genetics of COVID-19 Susceptibility and Manifestations

Background: Coronavirus 2019 (COVID-19, or SARS-CoV-2) is a serious public health problem, and genetics may play a role in how serious the illness becomes in certain people. Genes are the instructions that our body uses to grow and develop. Variations in our genes can cause medical conditions and may be the reason why some people get sicker than others. Objective: This study aims to learn more about the genetic contributions to the severity of COVID-19. We hope to use this information to develop therapies that reduce the severity of COVID-19 symptoms in some people. Eligibility: Anyone located in the United States who has tested positive for SARS-CoV-2 infection may be eligible to join (including NIH staff). Design: Participants will complete a questionnaire about their health history and COVID-19 symptoms. Participants will give a blood or saliva sample. It will be about 2 tablespoons of blood, or we will send a saliva collection kit. Researchers will use this blood or saliva sample to study the participant s DNA. The data about participants genes will be stored in a large database. The database will be shared with other qualified researchers who are trying to learn about COVID-19. Participants names and other personal details will not be shared. Instead, the data will be labeled with a code. Participants may be contacted by study team members for up to a year after they join the study.

COVID-19 Self-testing IMPROVE

The study aims to engage community partners to implement IMPROVE intervention and promote (COVID-19) rapid testing among vulnerable Asian Americans in the Greater Philadelphia Area and New York City

A Study to Learn About Flu and COVID-19 Vaccine Responses in Healthy People

This study is to learn about flu and COVID vaccines, either alone or when mixed together. Healthy people aged 18 or older can join. Participants will get one shot in each arm, either a flu or COVID vaccine, alone or mixed. The study lasts about 6 months, and participants need to visit the research site at least 3 times.

Smart Analysis and Decision-Making for Emerging Infectious Diseases

Emerging infectious diseases, such as COVID-19, mpox, and dengue fever, are characterized by rapid transmission, wide impact, and high uncertainty, posing ongoing threats to global public health. While China achieved significant success in COVID-19 control, the response also revealed key challenges, including fragmented information, delayed risk perception, experience-dependent assessment, and inefficiencies in complex decision-making. This study aims to establish a smart technology system covering the full chain of "risk perception-situational assessment-intelligent decision-making-comprehensive evaluation." Specific objectives include: Constructing a global disease burden database and knowledge graph for emerging infectious diseases; Developing early risk assessment models covering the full transmission spectrum (cross-species, imported, and local outbreak); Building an AI-driven collective intelligence decision-support tool for epidemic control; Developing precise intervention frameworks and comprehensive evaluation indicators for key populations (e.g., elderly, students); Integrating the above technologies into a multi-agent toolkit and evaluating its effectiveness through a cluster randomized controlled trial involving at least 36 district/county-level CDC clusters across five provinces/municipalities (Guangdong, Zhejiang, Hubei, Sichuan, and Shanghai). Three eligible CDC staff members will be enrolled from each participating cluster, including one CDC director or relevant leader responsible for infectious disease prevention and control and two professional staff members engaged in acute infectious disease surveillance, risk assessment, decision-making, or emergency response. Accordingly, at least 108 participants will be enrolled, and the final anticipated enrollment will be determined by the total number of participating clusters. The intervention group will use the smart toolkit alongside routine practices, while the control group will follow routine practices only. The primary outcome is response time for epidemic assessment and decision-making (hours from risk perception to decision completion). Secondary outcomes include epidemic control effectiveness, user satisfaction, and socioeconomic benefits. The intervention period is 3 months, starting around July 2026 and ending in December 2027. This study has been approved by the Peking University Biomedical Ethics Committee. The study does not involve individual patient data; all data are aggregated at the district/county level from CDC sources or publicly available data. Anonymous questionnaires do not collect any personal identifiable information.

Low Dose Whole Lung Radiation Therapy for Patients With COVID-19 and Respiratory Compromise

Low doses of radiation in the form of chest X-rays have been used to treat people with pneumonia. This treatment was found to be effective by reducing inflammation and with minimal side effects. However, it was an expensive treatment and was eventually replaced with less costly treatments such as antibiotics. Radiation has also been shown in some animal experiments to reduce some types of inflammation. Some patients diagnosed with COVID-19 pneumonia will experience worsening disease, which can become very serious, requiring the use of a ventilator. This is caused by inflammation in the lung from the virus and the immune system. For this study, the x-ray given is called radiation therapy. Radiation therapy uses high-energy X-ray beams from a large machine to target the lungs and reduce inflammation. Usually, it is given at much higher doses to treat cancers. The purpose of this study is to find out if adding a single treatment of low-dose x-rays to the lungs might reduce the amount of inflammation in the lungs from a COVID-19 infection, which could help a patient to breathe without use of a ventilator.

A Phase 1/2A, Randomized Study of a T Follicular Helper (TFH)-Targeting Genetic Vaccine Strategy Designed to Induce Broad, Durable Immune Responses

The goal of this clinical trial is to test two investigational COVID-19 booster vaccines, called CoTend-s3BXBB and CoTend-BXBB, in healthy volunteers ages 40-64. The CoTend-s3BXBB vaccine includes a component called "s3", which was designed to improve the body's response to the vaccine. CoTend-BXBB is the same vaccine without s3. The main questions the study aims to answer are: 1) Is the investigational vaccine safe? 2) Does "s3" lead to bigger, broader, and longer-lasting responses to the vaccine? 5 different doses of the vaccines will be studied. Participants will receive a single dose of either CoTend-s3BXBB, CoTend-BXBB, or placebo. Participants will be monitored for side effects. Saliva, nasal, and blood samples will be collected and immune responses to the vaccine will be measured.

Respiratory Virus Sampling and Repository

Background: Respiratory viruses, like the flu or COVID-19, cause significant illness and death worldwide. Researchers want to collect samples from people with respiratory virus infections. The samples in this natural history study will be used in future research. Objective: To obtain samples from people with respiratory viruses to learn more about respiratory virus infections and the immune responses against them. Eligibility: People aged 3 and older who have or are suspected to have a respiratory virus infection. Design: Participants will be screened with a medical record review. Participants will give blood samples. Data from their medical records will be collected. Participants will give nose samples. A soft plastic strip will be put into each nostril for a minute. They may also give nose, mouth (back of the throat), or saliva samples using swabs. Participants may receive kits by mail to collect nose and blood samples at home. They will use soft plastic strips to collect nose samples. To collect blood, they will prick their finger and dab a few drops of blood on four plastic tips. If a participant is in the hospital, air samples may be collected in their room. Participation will last for up to 2 years. After 2 years, participants may be asked for their consent again to give new samples and new medical data.

A Study to Learn About the Study Medicine (Nirmatrelvir Plus Ritonavir) in Pregnant Women With COVID-19

The purpose of this clinical trial is to learn about how study medicine (Paxlovid, which contains nirmatrelvir and ritonavir) is changed and eliminated from the body, as well as its safety, and the extent to which side effects can be tolerated for treatment of pregnant women with mild or moderate COVID-19 compared to non-pregnant women with mild or moderate COVID-19. This study is seeking participants who: * are expecting a healthy baby and are in their second or third trimester pregnancy and have mild or moderate COVID-19 * are not pregnant and have mild or moderate COVID-19. All participants in this study will take Paxlovid by mouth every 12 hours for 5 days. We will study the experiences of people receiving the study medicine. This will help us decide if the study medicine is safe. All participants will take part in this study for at least 34 days; pregnant participants will take part until their delivery, so that the study duration may be up to 6 months, depending on their delivery date. During this time, participants will have 7to 8 visits and, if pregnant, a visit at delivery. Around 2 to 3 visits and the delivery visit will be done in person (at the clinic or at the participant's home). The other 5 visits may be done over the phone, unless in-person visit is necessary as decided by the doctor. Blood samples will be collected on the first 4 to 5 study visits (and at other study visits, if necessary).

Study of Flonoltinib Maleate Tablets in the Treatment of Severe Novel Coronavirus (COVID-19) Infection

Flonoltinib Maleate (FM) is a triple-target inhibitor of JAK2, FLT3, and CDK6. It inhibited JAK2 with an IC50 of 0.8 nM, whereas its IC50 values against JAK1, JAK3, and TYK2 were 690 nM, 557 nM, and 65 nM, respectively, indicating high selectivity for JAK2 over other JAK family kinases. FM also inhibited FLT3 and CDK6 with IC50 values of 15 nM and 35 nM, respectively. In multiple pharmacodynamic models of inflammation, FM demonstrated favorable therapeutic efficacy and low toxicity.

Five-year Follow-up After Sars-CoV-2 Infection: Prevalence and Evolution of Post-acute Sequalae of COVID-19 (PASC)

This multicenter, observational, retrospective-prospective study aims to evaluate the prevalence and trajectory of Post-Acute Sequelae of COVID-19 (PASC) approximately 5 years after SARS-CoV-2 infection. The study will re-contact participants from an established cohort of more than 3,000 individuals with microbiologically confirmed SARS-CoV-2 infection, including both hospitalized and non-hospitalized patients, previously followed in dedicated post-COVID outpatient clinics. Participants will undergo a structured telephone interview approximately 60 ± 3 months after infection, and those meeting predefined clinical criteria will be invited to an in-person clinical assessment. The study will evaluate persistent symptoms, functional status, cognitive and nutritional status, frailty, sarcopenia, quality of life, healthcare resource utilization, and direct and indirect healthcare costs to characterize the long-term trajectory of PASC.

CArdiac REhabilitation for Building Exertional heArt Rate for Chronotropic Incompetence in Long COVID-19

The goal of this proof-of-concept clinical trial is to determine whether cardiac rehabilitation improves exercise capacity and chronotropic (heart rate) response to exercise among people with Long COVID. The study will include individuals with confirmed SARS-CoV-2 infection, symptoms not present prior to COVID-19 that are persistent for at least 3 months after acute infection ("Long COVID"), and who have reduced exercise capacity less than predicted and reduced heart rate response during cardiopulmonary exercise testing (CPET). In addition to the primary outcome of change in peak VO2, secondary outcomes will include change in symptoms including autonomic symptoms (COMPASS-31), anxiety (GAD-7), depression (PHQ-9), endothelial function with brachial artery flow-mediated dilation, and satisfaction (net-promotor score).

A Study on Paxlovid Once in the Market, to Observe Its Safety and Effectiveness in Patients Who Have a High Chance of Getting Severe COVID-19

The purpose of this study is to look at the safety and effectiveness of PAXLOVID in the real world and not in clinical studies. The study observes patients who have a high chance of getting severe COVID-19 in Korea. This study is seeking participants who are: * Patients with mild-to-moderate COVID-19 symptoms and at high chance of getting severe COVID-19, including hospitalization or death. * Patients who received, are currently receiving, or are going to receive PAXLOVID according to locally approved label. * Patients who have signed informed consent documents after understanding all the important parts of the study. All participants are treated according to routine medical practice and there are no scheduled visits required by this study. All participants will be studied for a follow-up period of 28 days from the last PAXLOVID treatment to understand the safety and the effectiveness of treatment.

COVID-19, Chronic Adaptation and Response to Exercise (COVID-CARE)

Background: People who are recovering from COVID-19 may continue to have problems that affect their daily life. For instance, they might feel overly tired. Researchers want to learn if exercise can help people recover after COVID-19 infection. Objective: To study if participation in a rehabilitation exercise program can help people recovering from COVID-19. Eligibility: Adults ages 18-80 with a lab-confirmed SARS-CoV2 infection (the virus that causes COVID-19), and are still having some symptoms. Design: Participants will have a medical history and physical exam. They will give blood and urine samples. They will have tests to measure heart and lung function. Their blood vessels will be assessed. Participants will have a computed tomography scan of the body. They will have an ultrasound of the muscles in their arms, legs, and chest. Participants will take a 6-minute walk test (6MWT). They will take other balance and movement tests. Participants will walk on a treadmill while hooked up to a monitor. Then they will be interviewed. It will be audio-recorded. Participants will complete surveys about their symptoms and daily activities. Participants will take a smell test. For this, they will identify different smells. They will also have memory, attention, and mental functioning tests. Participants will wear an activity monitor on their wrist 24 hours a day. They will exercise 3 times a week for 10 weeks by performing cardio-type exercise for 30 minutes. They will attend education classes once a week for 10 weeks. Participants will be contacted by phone or email every 3 months for 1 year after they complete the exercise part of the study. They will wear an activity monitor for up to 2 weeks.

An Online Game to Help Canadian Adults Identify COVID-19 Vaccine Misinformation With One-Month Follow-Up

COVID-19 vaccine misinformation contributed to vaccine hesitancy and preventable illness. This study tested whether a brief online game helps Canadian adults identify COVID-19 vaccine misinformation, and whether effects last one month. In the game, participants judged whether statements about COVID-19 vaccines were true or false and immediately received the correct answer with a brief evidence-based explanation, delivered in a game-like format with points, ranks, and feedback. Adults from a national non-probability online panel (n = 4,071) were randomized to the game, to the identical corrective content presented as a static blog post, or to a no-activity control. The game and blog groups were assessed immediately after the activity; all three groups were reassessed approximately one month later. The hypothesis was that gamified corrective information would produce more accurate knowledge than the same information presented as a static blog post and, at one month, than no activity. The primary outcome was accuracy in identifying true and false claims; vaccination intention, vaccine confidence, and self-reported vaccination were secondary outcomes. This is the fourth study in a research program whose first three trials are registered in a companion record.

"Artificial Intelligence-Based Data Analysis Results and Mortality Prediction in Covid-19 Patients in Intensive Care"

An artificial intelligence-based analysis will be performed using retrospective data of patients treated in adult intensive care units due to COVID-19. The dataset will include various parameters such as demographic information, laboratory results, vital signs, and clinical history. Among the machine learning models, logistic regression, support vector machines (SVM), decision trees, and deep learning techniques (e.g., artificial neural networks) will be utilized. The performance of these models will be compared with traditional scoring systems. As a result of the analysis, it is anticipated that AI-based models will provide higher accuracy and reliability in mortality prediction. In particular, it is expected that deep learning-based models will better capture complex relationships and predict the outcomes of critically ill patients with greater precision. AI-supported data analysis results have the potential to guide diagnosis and treatment strategies in high-risk intensive care patients and can contribute to mortality prediction. AI-based approaches in intensive care are likely to offer significant advantages in the management of critical diseases such as COVID-19. These methods have the potential to improve clinical decision-making processes by providing healthcare professionals with more precise and timely information.

Cognitive Rehabilitation in Post-COVID-19 Condition

Post-COVID-19 condition is frequently comprised of persistent cognitive sequela, including deficits in attention and executive functions (EFs). Goal Management Training (GMT) is a cognitive rehabilitation (CR) intervention for improving attention and EFs that has received empirical support in studies of other patient groups. The present study was designed to determine the efficacy of GMT for improving everyday attention and EFs in adults who experience persistent cognitive deficits after COVID-19. The study is a randomized controlled trial (RCT), comparing the efficacy of GMT to a wait list control condition (WL), for improving persistent cognitive sequela in post-COVID-19 condition. The study originally aimed to recruit 240 participants (120 per group). A total of 135 participants were enrolled, of whom 129 participants completed baseline assessments and were randomized to either group-based GMT (GMT; n = 64) or wait-list control (WL; n = 65), all aged 18 to 65 years with a history of laboratory- or home-test confirmed, SARS-CoV-2 infection and perceived attentional and EF difficulties in daily life that have lasted for at least two months and that cannot be explained by an alternative diagnosis. GMT was internet-delivered to groups of 4-7 participants in six weekly two-hour sessions. The primary outcome was the Metacognition Index of the Behavior Rating Inventory of Executive Function - Adult Version, a self-report measure assessing everyday EF difficulties, at six months post-treatment. Secondary outcomes included performance-based neurocognitive measures and rating scales of cognition, emotional health, quality of life, and fatigue. Secondary aims include to explore to what extent potential early change predicts outcome, and to examine what characterize those who profit from GMT, in addition to describe the neurocognitive and emotional health in a Covid-19 sample. The investigators will also examine potential long-term effects of GMT at 2- and 4-year follow-up.