Clinical Research Directory

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....

Natural History of Systemic and Nasal Mucosal Immunity to Influenza and SARS-CoV-2 in Adults After Vaccination

Background: Influenza (flu) vaccinations are required for all NIH staff members who have direct contact with patients. COVID-19 vaccines are recommended for persons 6 months of age and older. Researchers want to learn about immunity in NIH staff members who get a flu and/or COVID-19 vaccine. Objective: To understand what happens to the body s immune system throughout the year after getting the flu and/or COVID-19 vaccine. Eligibility: Adults ages 18 and older who work at NIH and plan to get the current season s flu vaccine and/or COVID-19 vaccine. Design: Participants will not get any vaccines as part of this study. Participants will be screened with a medical history and medicine review. They will get a survey via email. It will ask about their flu and SARS-CoV-2 history and vaccinations. Participants will have 12 monthly visits at NIH. If during that year they get both flu and SARS-COV-2 vaccines, their participation will be extended. Once a month, participants will be contacted. They will discuss any new medicines, recent vaccinations, or changes in medical history. Once a month, participants will have blood drawn. Once a month, participants will have nasal sampling. A small, flat absorptive strip will be placed in the nostril to soak up mucus. Participants will press against the outside of their nostril with their finger for 1 minute. Participants may be able to collect samples at home and mail them to NIH if they are not able to visit in person. Participation will last for about 12 13 months.

Noseguard for Prevention of Respiratory Infections in Real-World Use

This study is a prospective clinical study to evaluate the effectiveness of combined use of two nasal protective medical devices (Noseguard and Noseguard Night) in reducing respiratory infection rates, including COVID-19 and influenza, in real-world conditions. The study will also assess usability, satisfaction, and safety using electronic patient-reported outcomes (ePRO).

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 Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults

This is an open-label, first-in-human, dose-finding study to evaluate the safety and immunogenicity of a booster vaccination of Prime-2-CoV\_Beta in healthy participants.

Impact of Immunosuppression Adjustment on COVID-19 Vaccination Response in Kidney Transplant Recipients

Immunocompromised individuals, such as solid organ transplant (SOT) recipients are at high risk of COVID-19 associated complications and mortality. Retrospective studies so far have shown that a majority of SOT recipients did not develop appreciable anti-spike antibody response after a first, second, or even third dose of mRNA vaccine. Treatment with antimetabolites was associated with poor vaccine response. The goal of this study is 1) examine whether transient immunosuppression reduction improves the immune response to a third dose of SARS-CoV-2 mRNA vaccine in kidney transplant recipients and 2) to assess the safety of immunosuppression reduction before and after third dose SARS-CoV-2 mRNA vaccination.

Safety and Immunogenicity Trial of PepGNP-COVID19 Vaccine in Adults

This Phase 1 clinical trial will evaluate the safety, reactogenicity, and immunogenicity of PepGNP-COVID19, a synthetic nanoparticle-based, T cell-priming peptide vaccine against SARS-CoV-2, when administered as a booster dose in healthy adults. PepGNP-COVID19 is designed to induce broad and durable T cell-mediated immune responses by delivering conserved SARS-CoV-2 peptides covalently bound to carbohydrate-coated gold nanoparticles, with the goal of enhancing tissue-resident cytotoxic T lymphocytes in the respiratory tract and reducing the need for frequent antigen updates. This randomized, participant-blinded, dose-ranging, multi-site trial will enroll 60 healthy adults aged 18-64 years, with a target of 8 of 20 participants in each cohort being \> / = 50 years of age. Participants will receive a single intradermal injection of PepGNP-COVID19 at one of three dosage levels (0.83 nmol, 2.5 nmol, or 7.5 nmol in a volume of 0.05 mL). The primary objective is to evaluate the safety, reactogenicity, and tolerability of a single intradermal dose of PepGNP-COVID19 at three dosage levels in previously vaccinated healthy adults.

Antihistamines, Amantadine and Evolution of COVID-19

The rates of symptomatic COVID19 infection, hospital admission among COVID19 cases and survival would be quantified in patiens chronically treated with antihistamines or amantadine, with the aim of determining the role of antihistamines and amantadine in the evolution of COVID19.

A Safety and Immunogenicity Trial of Boost-2867 Vaccine, Via Intranasal and Intramuscular Routes

This phase 1 clinical trial will evaluate the safety, reactogenicity, and immunogenicity of Boost-2867, given intramuscular (IM) with or without adjuvant or intranasal (IN) without adjuvant, as a booster dose to previously vaccinated healthy adults. Each of the study sites will be assigned to enroll either only participants who will receive IM administration (up to 5 sites) or only participants who will receive IN administration (up to 5 sites); no site will administer both IM and IN study product administrations. Within the IM and IN Arms the cohorts will be sequentially enrolled. The study is designed as a non-randomized, open-label, dose-escalation clinical trial evaluating one dose level of Boost-2867 without adjuvant administered IM, three dose levels of Boost-2867 with adjuvant administered IM, and three dose levels of Boost-2867 without adjuvant administered IN. A sample size of 140 participants (20 participants per dose cohort) is anticipated. To evaluate for early safety signals for this first-in-human trial, study product administration of participants enrolled for IM administration and those enrolled for IN administration will proceed in a staged fashion. For Cohorts 1 (IM administration without adjuvant) and 5 (IN administration), which may be enrolled and dosed concurrently, 3 sentinel participants under 50 years of age will be enrolled in each Cohort over at least 2 days. For each of those Cohorts independently, a safety review of halting rules and clinical safety data through at least Day 8 will be conducted by the Protocol Safety Review Team (PSRT) prior to enrollment of the remainder of the cohort. Enrollment, dosing, and safety oversight for IM Cohorts 2, 3, and 4 will proceed in the same fashion as Cohort 1, except that sentinel enrollment need not be spaced over at least 2 days. Similarly, for IN Cohorts 6 and 7, enrollment and safety oversight will proceed in the same fashion as Cohort 5, except that sentinel enrollment need not be spaced over at least 2 days. The primary objectives are: 1) To evaluate the safety and reactogenicity of a single IM injection of three different antigen dose levels (5, 15, and 50 microgram) of Boost-2867 with Alhydrogel (R) (alum) and CpG 7909 adjuvants, and a single injection of 50 microgram Boost-2867 without adjuvant, in previously vaccinated healthy adults. 2) To evaluate the safety and reactogenicity of a single IN administration of three different antigen dose levels (20, 50, and 125 microgram) of Boost-2867 without adjuvant in previously vaccinated healthy adults.

A Study to Look at the Health Outcomes of Patients With COVID-19 and Influenza

The main purpose of this study is to understand: * the symptoms of COVID-19 or influenza- health-related outcomes of people with COVID-19 or influenza (influenza only included in updated study analyses) * the potential effects of COVID-19 vaccines in people with COVID-19 This study will enroll participants who are: * 18 years or older * reported to have symptoms with tests that have confirmed illness. The tests can be taken at any of CVS pharmacy COVID-19 or influenza test sites. The study will collect vaccine history information from participants who are ready to take part in the study. Participant will be emailed a form with questions about their health related to COVID-19 or influenza during multiple follow-ups over a 6-month period.

Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary Symptoms of Long COVID

The overarching goal of this study is to determine if baricitinib, as compared to placebo, will improve neurocognitive function, along with measures of physical function, quality of life, post-exertional malaise, effect of breathlessness on daily activities, post-COVID-19 symptom burden, and biomarkers of inflammation and viral measures, in participants with Long COVID.

COVID-19 Immunity and Changes Over Time

The risk of household spread of SARS-CoV-2 hinges on both the transmission dynamics of the virus circulating in the community as well as the seroprotection pattern of constituent members, which can be attributed to vaccination and previous infections. This study is conceptualised to assess the dynamicity of SARS-CoV-2 risk at the household level, through monitoring the pattern of seroprotection, in conjunction with the vaccination coverage, history of infection and exposure risk in the setting of Hong Kong.

Percutaneous Electrical Nerve Field Stimulation (PENFS) in Patients With Post Concussion Syndrome (PCS)

The purpose of this study is to test the effect of Auricular Percutaneous Electrical Nerve Field Stimulation (a Neurostim device) on children with pain and Post Concussion symptoms. An additional purpose of this study is to demonstrate that PENFS improves functioning in children with post Covid-19 symptoms.

Characteristics and Outcomes of Patients Admitted to Swedish Intensive Care Units for COVID-19

This is a registry-based cohort study of all adult patients (≥18 years) admitted to Swedish Intensive Care Units with confirmed SARS-CoV-2 infection and COVID-19 disease during the first 2 months of the 2020 pandemic. The main goal is to describe demographic characteristics, coexisting conditions, treatments and outcomes among critically ill patients with COVID-19. A secondary goal is to identify independent risk factors associated with increased mortality for these patients. Data regarding baseline characteristics including comorbidities, intensive care treatments and outcomes will be extracted. ICU lengths of stay and 30-day mortalities will be calculated. The primary outcome is 30-day all-cause mortality. THIS PART OF THE STUDY HAS BEEN COMPLETED. UPDATE 26 Feb 2022: Characteristics and outcomes of 'first wave' patients admitted to Swedish ICUs was published in Eur J Anaesthesiol. 2021 Apr 1;38(4):335-343. doi: 10.1097/EJA.0000000000001459. A description of the surge response and aggregated data outcomes in Scandinavian countries was published in https://onlinelibrary.wiley.com/doi/10.1111/aas.13983. UPDATE 13 Nov 2024: ADDITIONAL SUMMARY - EXTENDED INCLUSION PERIOD AND ADDITION OF LONG-TERM OUTCOMES, AND CRITICALLY ILL PATIENTS WITH INFLUENZA AND VIRAL PNEUMONITIS Due to the continued influx of patients requiring intensive care due to COVID-19, we extended the inclusion period to 31 Dec 2022. Thus this new cohort will include all patients admitted to ICUs in Sweden from 6 March 2020 to 31 Dec 2022. We will investigate short (30day mortality) and long-term outcomes (365d mortality and cardiovascular complications) of patients admitted to Swedish ICUs with confirmed SARS-CoV-2 infection and COVID-19 disease. In international research, the long-term effects of ICU-requiring COVID-19 are now highly topical. Long-term follow-up exceeding one year has not yet been conducted on any Swedish material. To concretely understand the actual implications of long-term outcomes, it is becoming almost standard to compare this patient group to ICU-requiring influenza + viral pneumonitis patients to some extent. We have applied for and obtained ethical approval to include this group as a potential comparator to COVID-19 patients. However, such comparisons require careful consideration of potential confounders, such as patient characteristics and socioeconomic factors. It is therefore crucial to both establish the disease burden for the population and relate it to a comparable patient group. Ethical approval and national data linkage approvals have now been obtained to extract this data from Statistics Sweden and the Swedish National Board of Health and Welfare registries. Data linkage was completed in October 2024.

Mitoquinone/Mitoquinol Mesylate as Oral and Safe Postexposure Prophylaxis for Covid-19

Adults who do not have major health, kidney, gastrointestinal disease will be randomized to receive oral mitoquinone/mitoquinol mesylate (Mito-MES) versus placebo to prevent the development and progression of COVID-19 after high-risk exposure to a person with confirmed SARS-CoV-2 infection.

I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critically Ill Patients

The goal of this project is to rapidly screen promising agents, in the setting of an adaptive platform trial, for treatment of critically ill COVID-19 patients. In this phase 2 platform design, agents will be identified with a signal suggesting a big impact on reducing mortality and the need for, as well as duration, of mechanical ventilation.

Improving Post COVID-19 Syndrome With Hyperbaric Oxygen Treatments

Over 500 million people have been infected with COVID-19, and to date, more than 6 million people have died. Many individuals who have recovered from COVID-19 continue to experience symptoms even after they have been "cured" of the disease. This condition is known as post COVID-19 condition, which can have serious health consequences. A common symptom among these individuals is chronic fatigue, characterized by persistent tiredness or lack of energy. This study aims to explore a novel treatment for symptoms of post COVID-19 condition, known as hyperbaric oxygen therapy. This approach has shown promise in helping people with post COVID-19 conditions and treating some other causes of fatigue. Hyperbaric oxygen therapy involves placing patients in a small chamber where they receive high oxygen gas levels. However, this treatment is expensive and time-consuming, and it is unclear if this treatment can be effectively assessed in a large-scale research study. This small study will help us decide if conducting a large research study is feasible. The investigators aim to assess if hyperbaric oxygen therapy can improve symptoms of post COVID-19 condition, such as fatigue.

Study of VYD2311 for the Prevention of COVID-19

The main purpose of this study is to test an investigational drug known as VYD2311, which is being developed to lower the risk of getting COVID-19. VYD2311 is a monoclonal antibody that attaches to the virus that causes COVID-19 and helps block it from entering your cells. It is being tested in adults and adolescents at least 12 years old. Participants in this study will be given a "study drug" that will be either VYD2311 or placebo. The study drug will be given as a shot into the muscle in the participant's upper thigh or upper arm once a month with a total of 3 shots during the study. This study will help researchers see how well VYD2311 works to prevent COVID-19 during the 90 days after the first shot. The study will also look at the safety and tolerability of VYD2311, how the study drug is processed by the body (pharmacokinetics), how the immune system reacts to the study drug (immunogenicity), and how well VYD2311 can block the virus from infecting cells (neutralization). To do these tests, your blood will be drawn at certain times during the study.

Effectiveness of mRNA-1273 Variant-Containing Vaccine Formulation Against Severe Outcomes in Adults Aged 50-64 Years Without Risk Factors for Severe COVID-19

The purpose of this pragmatic randomized trial is to evaluate the vaccine effectiveness of the COVID-19 vaccine, mRNA-1273, in adults aged 50-64 years without known risk factors for severe COVID-19 infection. Participants will be randomized 1:1 to either COVID-19 vaccine or no COVID-19 vaccine.

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.

Viral Infections in Healthy and Immunocompromised Hosts

Background: \- Viral infections are an important cause of illness and death in hospitalized patients as well as outpatients. New strains of viruses may appear and infect both healthy people and those with weak immune systems. A better understanding of these new virus strains (such as SARS-CoV-2, the virus that causes COVID-19) may help to control and prevent these infections. In particular, some viral infections that are less problematic in healthy persons can be life threatening in persons with weak immune systems, and viruses may be able to evolve more rapidly in persons with weak immune systems and therefore develop resistance to existing treatments. Researchers are interested in collecting samples and information from otherwise healthy persons or persons with weak immune systems to study the effects of viruses and their development. Objectives: \- To collect samples and data from individuals who have been exposed to or have contracted viral infections. Eligibility: * Individuals of all ages who have been diagnosed with a viral infection are suspected to have a viral infection, or have been in close contact with someone with a suspected or actual viral infection that is of interest to investigators in the Laboratory of Infectious Diseases. * Healthy persons and persons with weak immune systems (immunocompromised individuals) are eligible to participate. Design: * Participants will be pre-screened to determine if they meet the eligibility criteria for the trial. * If eligible, evaluation may include a medical chart review, a history and physical examination, review of clinical reports from outside hospitals and laboratories, and review of tissue biopsies. * Study procedures may include collection of blood, urine, saliva, nasal fluid sampling, throat swabs, stool, and genital swabs. For participants who have specimens collected as part of their medical care (e.g. wound swabs, spinal tap, bronchoscopy, liver biopsy etc.), researchers may use leftover specimens from the clinical laboratory for testing. * Specimens may be collected up to 4 times per week during the first 2 weeks after enrollment, and then as many as 2 times per week for up to 2 years. Some participants may be asked to continue providing specimens if there is concern for relapse or recurrence of the infection. * Treatment is not offered under this study.

COVID-19 Reactogenicity

The purpose of this study is to compare post-vaccination reactions between the protein-based Novavax vaccine and the mNEXSPIKE mRNA-1283 vaccine. Specifically, the study aims to determine the rate of participant-reported symptoms associated with each type of vaccine.

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.