Around the world, researchers are working extremely hard to develop new treatments and interventions for COVID-19 with new clinical trials opening nearly every day. This directory provides you with information, including enrollment detail, about these trials. In some cases, researchers are able to offer expanded access (sometimes called compassionate use) to an investigational drug when a patient cannot participate in a clinical trial.
The information provided here is drawn from ClinicalTrials.gov. If you do not find a satisfactory expanded access program here, please search in our COVID Company Directory. Some companies consider expanded access requests for single patients, even if they do not show an active expanded access listing in this database. Please contact the company directly to explore the possibility of expanded access.
Emergency INDs
To learn how to apply for expanded access, please visit our Guides designed to walk healthcare providers, patients and/or caregivers through the process of applying for expanded access. Please note that given the situation with COVID-19 and the need to move as fast as possible, many physicians are requesting expanded access for emergency use. In these cases, FDA will authorize treatment by telephone and treatment can start immediately. For more details, consult FDA guidance. Emergency IND is the common route that patients are receiving convalescent plasma.
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Displaying 370 of 482KU Leuven
This study is a longitudinal cohort study which investigates the effect of COVID-19 in ambulatory care. This study aims to assess the effect of COVID-19 beyond the acute phase, i.e. on long-term symptoms, respiratory and cardiovascular health, use of health services, and quality of life.
Faculty of Medicine , Kafrelshiekh University, Egypt.
Utilizing the crosstalk among aerosolized phenformin, methylene blue, photodynamic therapy , zinc and potassium for treating severe COVID-19 infection and its inflammatory complication Amr Ahmed(1), Mahmoud Elkazzaz(2), Tamer Haydara(3), and Abdullah Alkattan(4) 1. Director of tuberculosis program Ghubera, public health department ,First health cluster ,Ministry of health ,Saudia Arabia. 2. Department of chemistry and biochemistry, Faculty of Science, Damietta University, Egypt. 3. Department of Internal Medicine, Faculty of Medicine, Kafrelsheikh University, Egypt. 4. Ministry of Health, Riyadh, Saudi Arabia. SARS-CoV-2 represents the largest current health challenge for the society. Moreover, numerous variants of the virus that causes COVID-19 are being tracked in the United States and globally during this pandemic. Here, we will use combination therapy which involve agents with significant activity and different mechanisms of action against covid-19 and its inflammatory complication. Excessive activities of cysteinyl cathepsins (CysCts) contribute to the progress of many diseases. however, therapeutic inhibition has been problematic. Cathepsin L are crucial in terms of the endocytosis by cleaving the spike protein, which permits viral membrane fusion with endosomal membrane, and succeeded by the releasing of viral genome to the host cell. Thereby, inhibition of cathepsin L may be advantageous in terms of decreasing infection caused by SARS-CoV-2. It is well known that zinc (Zn) possesses a variety of direct and indirect antiviral properties, which are realized through different mechanisms. Administration of Zn supplement has a potential to enhance antiviral immunity and to restore depleted immune cell function, in particular in immunocompromised patients. It has been found that Zn 2+ deficiency leads to an exaggerated activity of Cysteine cathepsin increasing the autoimmune/inflammatory response. . Zn2+ is a natural inhibitor of proteases with CysHis dyads or CysHis(Xaa) triads. cysteine protease Cathepsin L (CatL) involvement with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 from different points of view. At this purpose Zn 2+ metal can be safely combined with phenformin a drug that increases the anti-proteolytic effect of endogenous Zn 2+ lowering the excessive activity of some CysCts.; A study found that phenformin-Zn2+ complex is identified as a modifiable pharmacophore for synthesis of therapeutic CysCt inhibitors with a wide range of potencies and specificities. Phenformin stabilizes a "Zn2+ sandwich" between the drug and protease active site. Additionally, phenformin was found to be potent inhibitor of IL-6 R, with phenformin (100 µM) treatment for 48 h, decreased IL-6R expression in ANBL6, RPMI, U266, MM1S, and JJN3 was 5.51 (p = 0.0025), 3.03 (p = 0.0005), 1.55 (p < 0.05), 2.09 (p = 0.0082) and 1.19-fold, respectively. Furthermore, phenformin was discovered to potentially and strongly bind to ACE2 receptors, according to a docking research being conducted by the principle investigators of this clinical study therefore, Phenformin is expected to potentially attach to ACE2 receptors and lead to its downregulation, an inhibitory mechanism which may combat and block COVID-19 infection in lung epithelial cells. Phenformin may induce lactic acidosis therefore according to the principal investigator The phenformin will be utilized as aerosolized by inhalation for COVID-19 treatment and this may be an effective novel treatment strategy that would limit the risk of systemic side-effects associated with biguanides due to the low inhaled dose. In addition, we will use aerosolized phenformin in combination with methylene blue. A study found that a very marked improvement in lactate and pyruvate concentrations occurred within six hours of the beginning of méthylène blue administration in human . It has been known for some time that méthylène blue is a moderately efficient hydrogen acceptor in several enzyme sys¬ tems and significantly reduce oxidative stress by scavenging ROS. Moreover, Methylene Blue has antiviral activity and was found to Inhibit the Spike-ACE2 Protein-Protein Interaction-a Mechanism that can contribute to its Antiviral Activity Against COVID-19 For many reasons, methylene blue is a promising drug for an active treatment against SARS-CoV-2 . Since methylene blue can work as a photosensitizer, photodynamic therapy as an antiviral treatment has great potential in the treatment of COVID-19.. This clinical study will investigate the effectiveness of SARS-CoV-2 infected people treatment using methylene blue and the following photodynamic therapy after that our clinically approved patients will receive phenformin and zinc . But methylene blue may lead to lowering in potassium concentration.Therefore, we will add potassium supplement to this combination.
Kafrelsheikh University
Investigating the potential role of Aerosolized retinoic acid, a potent Vitamin A metabolite for treating COVID-19 Anosmia and retinoic acid insufficiency .A novel approach for regaining Sense of Smell. Mahmoud ELkazzaz(1),Tamer Haydara(2), Abedelaziz Elsayed(3) ,Yousry Abo-amer(4), Hesham Attia(5), Quan Liu(6) and Amr Ahmed(7) 1. Department of chemistry and biochemistry, Faculty of Science, Damietta University, Egypt. 2. Department of Internal Medicine, Faculty of Medicine, Kafrelsheikh University, Egypt 3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tanta University, Egypt. 4. Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital, Egypt 5. Department of Immunology and Parasitology, Faculty of Science, Cairo University, Egypt. 6. School of Life Sciences and Engineering, Foshan University, Laboratory of Emerging Infectious Disease, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China. 7. Director of tuberculosis program Ghubera, public health department ,First health cluster ,Ministry of health ,Saudia Arabia. - Very important Note: This clinical study is the first clinical study in literature (First posted August 12, 2021) which demonstrated depending on molecular findings that Vitamin A /Retinoic Acid will treat smell loss resulted by COVID-19 Recent rapidly accumulating evidences and reports indicate that partial loss of the sense of smell or even total anosmia are early markers of SARS-CoV-2 infection and frequently reported symptoms associated with the COVID-19 pandemic (Lechien J. R et al., 2020) However, the cellular mechanisms of this phenomenon are unknown. The rates of insomnia and depression were 26.45% and 9.92% in the COVID-19 patients after recovery. Therefore, finding an effective treatment for COVID-19 Anosmia is a critical point. Although, ACE2 has been identified as the principal host cell receptor of 2019-nCoV, and it is thought to play a critical role in the virus's entrance into the cell and subsequent infection, many cells can be infected by COVID-19 while also expressing little or no ACE2. Even though the COVID-19 entry receptor, angiotensin-converting enzyme 2 (ACE2), is not expressed in the receptor of olfactory neurons, or its synthesis is limited to to a minor fraction of these neurons.of these neurons, COVID-19 infection causes a loss of smell (anosmia) (Katarzyna Bilinska et al.,2021). Our recent findings showed that COVID-19 binds directly to STRA6 receptors of retinol leading to retinol depletion and retinoic acid insufficiency (M Elkazzaz et al,. 2021) . Retinoic acid insufficiency in the olfactory epithelium, both in mouse and chick models, causes progenitor cell maintenance failure and, consequently, olfactory neurons differentiation is not maintained . An explant system, showed that renewal of olfactory neurons is inhibited if retinoic acid synthesis was failed in the olfactory epithelium (Paschaki M et al., 2013) . It's worth noting that vitamin A shortage also causes olfactory and taste problems, In a study by Garrett-Laster et al., (1984), the patients had vitamin A deficiency because of malnutrition and alcoholic liver cirrhosis; they lost their sense of smell after that disorder. LaMantia and Rawson et al.,( 2007) reported that administration of retinoid acid after the damage of olfactory system motivates an immune response and produces a more quick recovery of olfactoryguided behavior. It was showed that Isotretinoin improved the significantly performance of patients in the olfactory test(Demet Kartal et al.,2017) Moreover, there is increasing evidence that retinoic acid (atRA) influences gene expression of components of renin-angiotensin system (RAS), which plays a pivotal role in the pathophysiology of essential hypertension. Retinoic acid induced ACE2 expression in different animal models. Moreover, a study suggests that topical retinoids may have applicability in promoting sinus regeneration and wound healing. In a study comparing treated and untreated nasal mucosa ,untreated regenerated mucosa showed expected changes of submucosal gland loss, basal lamina and lamina propria fibrosis and loss of cilia. Reinoic acid treatment appeared to result in better mucosal regeneration marked by less cellular atypia and fibrosis(Mendy S. Maccabee et al,. 2003).. Aerosolized retinoic acid will have an effective role in treating post COVID-19 anosmia (loss of smell) via upregulating ACE2, STRA 6 and regenerating of olfactory receptors and olfactory sensory cells and neurons.
Yueh-Lin Hsu
With the aging of today's population, stroke is the top three causes of disability and death among people over the age of 60 in the world. About 5.5 million people die each year from strokes in Taiwan, and Taiwan's top ten causes of death in cerebrovascular disease rank fourth in the world. Constipation is the most common complication of stroke patients and increases the risk of brain damage and re-stroke. Although the clinical use of drugs can relieve intestinal symptoms, there is also a risk of potential side effects. The systematic literature points out that the use of acupoint stimulation can improve spontaneous bowel movements and promote bowel motility, but there is no conclusion on effective acupuncture points. Therefore, the purpose of this study is to improve the constipation of patients with stroke by non-invasive and precise acupoint care. This study used a single-blind randomized control trial. The neurosurgery ward of a medical center in the north was used as the research site, and patients with ischemic stroke were used as the research objects. The experimental group received precision acupoint care, and the control group received routine care. The questionnaire was used to collect basic patient information (basic attributes, disease care and TCM constitution), and gut-related assessments. Data analysis was performed using IBM SPSS 22.0 software for descriptive statistical analysis and inferential statistical analysis, and p
Istanbul Gelisim University
Aerobic Versus Anaerobic Exercise on Immune Functions and Disease Severity in Patients With COVID-19
Participants were assigned randomly into two groups, aerobic exercise and resistance exercise groups. All participants in both groups followed the WHO guidelines of quarantine and used standardized medications given by the physician according to the Turkish Ministry of Health guidelines, including the Hydroxyclorocin Sulphate 200 Mg Film Tablet (Plaquenil 200 Mg Film Tablet). The dose was 2 times/ day, 200Mg/time, for 5 days. Besides, the aerobic exercise group performed moderate-intensity aerobic exercises for 40 min/ 3 sessions/week, 40 minute/session, and the resistance exercise groups 40 min/ 3 sessions/week, 40 minute/session.
Saglik Bilimleri Universitesi
The primary aim of our study is to understand the effects of Covid-19 disease on vascular inflammation and coagulation cascade, and secondarily, to investigate its utility in predicting disease prognosis by analyzing serum PAI-1 levels in patients with different severity. The study is planned as a prospective, cross-sectional study that will include patients admitted to Covid-19 services between January 18, 2021, and August 30, 2021. A total of 80 volunteers will be enrolled in the trial whose age, gender, and BMI are planned to be matched.The study will be conducted on four groups. Group 1 (n=20; with mild symptoms), Group 2 (n=20; with moderate symptoms), Group 3 (n=20; with severe symptoms) and Group 4 (n=20; Control group). All participants who accepted the study will have their sociodemographic data, medical history, and vital signs (respiratory rate, saturation, temperature, and blood pressure values) recorded at the start of the study. The pulmonologist in the study will also classify the patient group's chest X-ray and chest tomography findings and the thymus gland dimensions. After all four groups of patients have given their consent for the study, a sample of 5cc blood will be obtained once for the PAI-1 analysis.
Universita di Verona
This randomized controlled trial will evaluate the implementation and (cost-)effectiveness of the culturally and contextually adapted Doing What Matters in times of stress (DWM) and Problem Management Plus (PM+) stepped-care programs amongst asylum seekers, refugees, and/or migrants living in Italy. Outcomes include mental health, resilience, wellbeing, health inequalities, and costs to health systems.
Chinese University of Hong Kong
Safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may reduce the transmission of and achieve population immunity against the COVID-19 pandemic, which accounted for more than 3.75million deaths worldwide. With World Health Organization's (WHO) effort on ensuring equitable access to COVID-19 vaccines, vaccination rate may increase in the near future. On the other hand, vaccination hesitancy has emerged as a major hindrance on the global vaccination campaigns in certain areas due to safety concerns, social factors, and public health policies. For instance, a recent survey conducted in Hong Kong showed a low vaccine acceptance rate of 37%. Long-term safety concerns and post-vaccination events relayed by the social media maybe reasons for vaccination hesitancy. Among which, cerebrovascular accidents (CVA) after vaccination were one of the most frequently reported post-vaccination events. These reports ranged from ischemic strokes in elderly patients with multiple cardiovascular co-morbidities, to hemorrhage strokes in otherwise "young-and-fit" adults. While many of these events were investigated by the COVID-19 immunization expert committee, an important premise to address the apprehension of CVA after vaccination is the provision of evidence-based information of the impact of COVID-19 vaccines on brain health. In this prospective, longitudinal, observational study, we aim to elucidate the relationship between COVID-19 vaccines and cerebrovascular health in healthy citizens in a population-based cohort.
NeuroRx, Inc.
IIBR-100 (VSV-ΔG) is a self-propagating live virus vaccine that contains the spike protein of the Wuhan wild-type SARS-CoV-2 virus. Preclinical and phase 1/2 trials have demonstrated no safety signals of concern and have further demonstrated immunologic response that approximates the response seen in convalescent individuals. The purpose of this phase 2b/3 trial is to document the non-inferiority of IIBR-100 vs. an already-approved vaccine for COVID-19.
Mahmoud Ramadan mohamed Elkazzaz
T-cell exhaustion may limit long-term immunity in COVID-19 patients. T cells can lose their ability to fight viruses and tumors when they have prolonged exposure to these enemies. New data suggests people who experience mild COVID-19 symptoms show the molecular signs of exhausted memory T cells and therefore could have a reduced ability to fight reinfection. On contrary people who develop severe COVID-19 symptoms may be better protected from reinfection. A recent study reported that the 82.1% of COVID-19 cases displayed low circulating lymphocyte counts . It has been reported that, in the case of chronic viruses, continuous PD-1 expression causes T-cell exhaustion, and impairs the ability of killing the infectious cells . The adumbration of patients with COVID-19 is characterized by a diminished lymphocyte percentage, with a similar proportion of CD4+ and CD8+ T-cells. The quantity of T-cells, mostly CD8+ T-cells, presenting high expression rates of late activity marker CD25 and exhaustion marker PD-1 increases. Therefore, SARS-CoV-2 is able to make changes by modifying the acquired immune system, including B and T cells. According to experiments, PD-1's expression, as an important factor in the induction and maintenance of circumferential tolerance keeping the stability of T-cells, has been found to have a higher percentage in different cells of COVID-19 patients. In an experiment conducted by Diao et al., on the patients with SARS-CoV-2, it was observed that the expression of PD-1 on the surface of T-cells was increased significantly; it was also shown that during the SARS-CoV-2 -induced disease, additional expressions of PD-1 and Tim-3 on the T-cells were directly related to the disease's severity; the factors that were also increased in other viral infections. T cell exhaustion" phenomenon could be reversed relatively easily, for example when the T cells are no longer exposed to the virus or tumor. But unfortunately, although exhausted T cells recovered from chronic infection (REC-TEX) regain some function and features of memory T cells (TMEM), they retain epigenetic scars indicating the control of gene expression is "locked in" to their exhaustion history. Once T cells become exhausted, they remain fundamentally 'wired' to be exhausted-thus it may be hard to get them to become effective virus- and cancer-fighters again," said John Wherry, PhD, chair of the department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania. Furthermore, COVID-19 may infect T lymphocyte cells and induce apoptosis and apoptotic markers. Lymphocytopenia was also found in the Middle East respiratory syndrome (MERS) cases. MERS-CoV can directly infect human primary T lymphocytes and induce T-cell apoptosis through extrinsic and intrinsic apoptosis pathways, but it cannot replicate in T lymphocytes. However, it is unclear whether SARS-CoV-2 can also infect T cells, resulting in lymphocytopenia. A study showed that T cells express a very low expression level of hACE2 on its cell surface and T-cell lines were significantly more sensitive to SARS-CoV-2 infection when compared with SARS-CoV . In other words, these results tell us that T lymphocytes may be more permissive to SARS-CoV-2 infection. Therefore, it is plausible that the S protein of SARS-CoV-2 might mediate potent infectivity, even on cells expressing low hACE2, which would, in turn, explain why the transmission rate of SARS-CoV-2 is so high. Through recent advances in genomic editing, T cells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging (post-)transcriptional mechanisms to enhance T cell cytokine production, the retargeting of T cell antigen specificity or rendering T cells refractive to inhibitory receptor signaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genome editing might provide novel strategies for inducing long term immunity against COVID-19.Immunotherapies with autologous T cells have become a powerful treatment option for many diseases like viral infection or cancer. These include the adoptive isolation and transfer of naturally-occurring virus/tumor-specific T cells and the transfer of T lymphocytes that have been genetically modified . According to the investigator, exhausted virus-reactive CD8+ memory T cells will be isolated from patients with mild infection using a modified antigen-reactive T cell enrichment (ARTE) assay. exhausted virus-reactive CD8+ memory T cells will be collected and both Programmed cell death protein 1(PDCD1) gene and ACE2 gene will be knocked out by CRISPR Cas9 in the laboratory. The lymphocytes will be selected and expanded ex vivo and infused back into patients.