Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| EN21-00050 | Other Identifier | Universidad Autónoma de Nuevo León |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Laboratorio de Inmunologia y Virologia - UANL | OTHER |
| Hospital Universitario Dr. Jose E. Gonzalez | OTHER |
Not provided
Not provided
Not provided
In this study, the effects of IMMUNEPOTENT-CRP (I-CRP), a dialyzable leukocyte extract (DLE) derived from bovine spleen cells, on the levels of key inflammatory cytokines in outpatients with COVID-19 were examined. I-CRP has been previously studied for its ability to regulate the immune system in other conditions, such as cancer and sepsis. Based on its potential to reduce harmful inflammation, the study aimed to determine if similar benefits could be observed in COVID-19 outpatients.
Outpatients with mild to moderate COVID-19 symptoms and a confirmed SARS-CoV-2 infection were enrolled. These patients were randomly assigned to receive either IMMUNEPOTENT-CRP (I-CRP) or a placebo over a 14-day period. The study was double-blind, meaning neither the patients nor the researchers knew who was receiving I-CRP or placebo, ensuring unbiased results. The main objective of the study was to measure changes in the levels of specific cytokines and chemokines in the blood-IL-1β, IL-6, IL-10, TNF-α, IFN-α, IFN-γ, and IL-8-which are key players in the inflammatory response linked to severe COVID-19 cases. High levels of these molecules are associated with worse outcomes and more severe symptoms. Additionally, other markers of inflammation and immune system activity, such as lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hs-CRP), ferritin, and D-dimer, were measured, as these are commonly used to assess the severity of inflammation and risk of complications in COVID-19 patients.
Throughout the study, outpatients were regularly monitored for symptoms, and their vital signs-such as oxygen levels and body temperature-were checked during home visits. Blood samples were collected at different intervals to measure cytokine levels and the other included inflammatory markers. Patients were also tested four times for the presence of the virus to determine their infection status during the follow-up period.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| I-CRP group | Experimental | IMMUNEPOTENT-CRP (I-CRP) was supplied in a 5 Unit (U) per vial presentation. One U is defined as the lyophilized product obtained from the dialysis of 1×10^8 bovine spleen cells. The dosing schedule extended over 14 days. On the first day (Day 0), outpatients ingested seven doses at two-hour intervals each one. From days one through four, four doses were taken one every four hours, and from days five to thirteen, three doses were consumed one every eight hours. |
|
| Placebo control | Placebo Comparator | The placebo was prepared from a lyophilized corn starch extract and was provided in an identical appearance and presentation to IMMUNEPOTENT-CRP (I-CRP). The dosing schedule extended over 14 days. On the first day (Day 0), outpatients ingested seven doses at two-hour intervals each one. From days one through four, four doses were taken one every four hours, and from days five to thirteen, three doses were consumed one every eight hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IMMUNEPOTENT-CRP (I-CRP) | Biological | IMMUNEPOTENT-CRP (I-CRP), a bovine dialyzable leukocyte extract (DLE) obtained from disrupted spleen cells, is a mixture of low-molecular-weight peptides (<12 kDa) that exhibit non-specific immunomodulatory properties. |
| Measure | Description | Time Frame |
|---|---|---|
| Cytokine and Chemokine Serum Levels Evaluation | Serum levels of IL-1β, IL-6, IL-10, TNF-α, IFN-α, IFN-γ, and IL-8 were measured using the Human Cytokine/Chemokine Magnetic Bead Panel (Milliplex, Darmstadt, Germany). Cytokine and chemokine concentrations in the serum are expressed in pg/mL. | Assessments were performed at baseline (Day 0), and during the intervention period at Day 7 and Day 14. |
| Measure | Description | Time Frame |
|---|---|---|
| Lactate Dehydrogenase (LDH) Levels | Plasma levels of lactate dehydrogenase (LDH) were measured using standard biochemistry tests. Reference normal values are 230-460 mg/dL. | Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. |
| High-Sensitivity C-Reactive Protein (hs-CRP) Levels |
Not provided
Outpatients Inclusion Criteria:
Outpatients Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Cristina Rodriguez-Padilla, Ph.D. | Universidad Autonoma de Nuevo Leon | Study Director |
| Rene Rodriguez-Gutierrez, Ph.D. | Universidad Autonoma de Nuevo Leon | Study Chair |
| Jose Manuel Vazquez-Guillen, Ph.D. | Universidad Autonoma de Nuevo Leon | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario "Dr. Jose E. Gonzalez", Universidad Autonoma de Nuevo Leon | Monterrey | Nuevo León | 64460 | Mexico | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Franco-Molina MA, Santana-KrÃmskaya SE, Zarate-Triviño DG, Zapata-Benavides P, Hernández-MartÃnez SP, Cervantes-Wong F, et al. Bovine dialyzable leukocyte extract immunepotent CRP: Evaluation of biological activity of the modified product. Appl Sci 2021;11. https://doi.org/10.3390/app11083505. | ||
| 31013404 | Background | Ayala MC, Gonzalez NM, Palacios G, Rivera-Morales LG, Rodriguez-Padilla C. [Dialyzed leukocyte extracts for the treatment of recurrent and severe infections in pediatric patients with cellular immunodeficiency: 15 years of experience]. Rev Alerg Mex. 2019 Jan-Mar;66(1):27-37. doi: 10.29262/ram.v66i1.531. Spanish. | |
| 15454111 |
Not provided
Not provided
The individual participant data (IPD) to be shared with other researchers will include the following variables related to the study participants:
Prior to sharing the data, all identifiable participant information will be anonymized to ensure privacy and confidentiality. Measures will be taken to prevent any possible re-identification of participants.
The data will be available for a period of 3 years following the publication of the study.
The IPD will be made available to other researchers after the publication of the study results in a peer-reviewed scientific journal. Data will be available upon reasonable request and subject to approval by the study's Ethics Committee. Interested researchers may request access to the IPD by contacting the principal investigator of the study. Requests must include a clear description of the research purpose, and researchers must agree to use the data only for the specified purposes and comply with applicable ethical and data protection regulations.
Not provided
Not provided
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D000080424 | Cytokine Release Syndrome |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo Comparator | Biological | The placebo was prepared from a lyophilized corn starch extract and was provided in an identical appearance and presentation to IMMUNEPOTENT-CRP (I-CRP). |
|
Serum levels of high-sensitivity C-reactive protein (hs-CRP) were measured using standard biochemistry tests. Reference normal values are 0.0-0.3 mg/dL. |
| Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. |
| Ferritin Levels | Serum levels of ferritin were measured using standard biochemistry tests. Reference normal values are 13-150 ng/mL. | Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. |
| D-Dimer Levels | Plasma levels of D-dimer were measured using standard biochemistry tests. Reference normal values are 0.0-0.5 μg/mL. | Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period. |
| Lymphocyte Subpopulations | The percentages (%) of lymphocyte subpopulations in whole blood were determined using the BD Multitest 6-color TBNK reagent kit (BD Biosciences, San Jose, USA) and analyzed with the BD FACSCantoâ„¢ flow cytometer (BD Biosciences). | Lymphocyte subpopulation counts in whole blood were measured at baseline (Day 0), Day 7, and Day 14 during the administration of I-CRP or placebo. |
| SARS-CoV-2 Infection Status Evaluation | Nasopharyngeal/oropharyngeal (NP/OP) flocked swabs collected in 3-5 mL of viral transport medium (VTM) were used to determine SARS-CoV-2 infection status via RT-qPCR. The 2019-nCoV CDC EUA Kit (IDT, Coralville, USA) primers and probe set were used for the assay. RT-qPCR results with a sigmoidal amplification curve and a cycle threshold (Ct) value of ≤37 were considered positive for SARS-CoV-2, while Ct values of 38 and above were considered negative. | SARS-CoV-2 infection status was evaluated at baseline (Day 0), Day 7, Day 14, and Day 30 during outpatient follow-up. |
| Laboratorio de Inmunologia y Virologia |
| San Nicolás de los Garza |
| Nuevo León |
| 66450 |
| Mexico |
| Background |
| Franco-Molina MA, Mendoza-Gamboa E, Castillo-Leon L, Tamez-Guerra RS, Rodriguez-Padilla C. Bovine dialyzable leukocyte extract protects against LPS-induced, murine endotoxic shock. Int Immunopharmacol. 2004 Dec 15;4(13):1577-86. doi: 10.1016/j.intimp.2004.06.014. |
| 16997795 | Background | Armides Franco-Molina M, Mendoza-Gamboa E, Castillo-Tello P, Tamez-Guerra RS, Villarreal-Trevino L, Tijerina-Menchaca R, Castillo-Leon L, Zapata-Benavides P, Rodriguez-Padilla C. In vitro antibacterial activity of bovine dialyzable leukocyte extract. Immunopharmacol Immunotoxicol. 2006;28(3):471-83. doi: 10.1080/08923970600928072. |
| 16923617 | Background | Franco-Molina MA, Mendoza-Gamboa E, Miranda-Hernandez D, Zapata-Benavides P, Castillo-Leon L, Isaza-Brando C, Tamez-Guerra RS, Rodriguez-Padilla C. In vitro effects of bovine dialyzable leukocyte extract (bDLE) in cancer cells. Cytotherapy. 2006;8(4):408-14. doi: 10.1080/14653240600847266. |
| 18368600 | Background | Mendoza-Gamboa E, Franco-Molina MA, Zapata-Benavides P, Castillo-Tello P, Vera-Garcia ME, Tamez-Guerra RS, Rodriguez-Padilla C. Bovine dialyzable leukocyte extract modulates AP-1 DNA-binding activity and nuclear transcription factor expression in MCF-7 breast cancer cells. Cytotherapy. 2008;10(2):212-9. doi: 10.1080/14653240801891659. |
| 20205507 | Background | Franco-Molina MA, Mendoza-Gamboa E, Zapata-Benavides P, Castillo-Tello P, Isaza-Brando CE, Zamora-Avila D, Rivera-Morales LG, Miranda-Hernandez DF, Sierra-Rivera CA, Vera-Garcia ME, Tamez-Guerra RS, Rodriguez-Padilla C. Antiangiogenic and antitumor effects of IMMUNEPOTENT CRP in murine melanoma. Immunopharmacol Immunotoxicol. 2010 Dec;32(4):637-46. doi: 10.3109/08923971003663253. Epub 2010 Mar 5. |
| 22044844 | Background | Lara HH, Ixtepan-Turrent L, Garza-Trevino EN, Badillo-Almaraz JI, Rodriguez-Padilla C. Antiviral mode of action of bovine dialyzable leukocyte extract against human immunodeficiency virus type 1 infection. BMC Res Notes. 2011 Nov 1;4:474. doi: 10.1186/1756-0500-4-474. |
| 28101208 | Background | Sierra-Rivera CA, Franco-Molina MA, Mendoza-Gamboa E, Zapata-Benavides P, Santaolalla-Tapia J, Coronado-Cerda EE, Tamez-Guerra RS, Rodriguez-Padilla C. Effect of bovine dialyzable leukocyte extract on induction of cell differentiation and death in K562 human chronic myelogenous leukemia cells. Oncol Lett. 2016 Dec;12(6):4449-4460. doi: 10.3892/ol.2016.5285. Epub 2016 Oct 18. |
| 37223080 | Background | Lorenzo-Anota HY, Reyes-Ruiz A, Calvillo-Rodriguez KM, Mendoza-Reveles R, Urdaneta-Peinado AP, Alvarez-Valadez KM, Martinez-Torres AC, Rodriguez-Padilla C. IMMUNEPOTENT CRP increases intracellular calcium through ER-calcium channels, leading to ROS production and cell death in breast cancer and leukemic cell lines. EXCLI J. 2023 Mar 16;22:352-366. doi: 10.17179/excli2022-5568. eCollection 2023. |
| 37240318 | Background | Garcia Coronado PL, Franco Molina MA, Zarate Trivino DG, Menchaca Arredondo JL, Zapata Benavides P, Rodriguez Padilla C. Putative Wound Healing Induction Functions of Exosomes Isolated from IMMUNEPOTENT CRP. Int J Mol Sci. 2023 May 18;24(10):8971. doi: 10.3390/ijms24108971. |
| 38077402 | Background | Calvillo-Rodriguez KM, Lorenzo-Anota HY, Rodriguez-Padilla C, Martinez-Torres AC, Scott-Algara D. Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system. Front Immunol. 2023 Nov 23;14:1294434. doi: 10.3389/fimmu.2023.1294434. eCollection 2023. |
| 27191003 | Background | Coronado-Cerda EE, Franco-Molina MA, Mendoza-Gamboa E, Prado-Garcia H, Rivera-Morales LG, Zapata-Benavides P, Rodriguez-Salazar Mdel C, Caballero-Hernandez D, Tamez-Guerra RS, Rodriguez-Padilla C. In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil. J Immunol Res. 2016;2016:6942321. doi: 10.1155/2016/6942321. Epub 2016 Apr 17. |
| 28693241 | Background | Rodriguez-Salazar MDC, Franco-Molina MA, Mendoza-Gamboa E, Martinez-Torres AC, Zapata-Benavides P, Lopez-Gonzalez JS, Coronado-Cerda EE, Alcocer-Gonzalez JM, Tamez-Guerra RS, Rodriguez-Padilla C. The novel immunomodulator IMMUNEPOTENT CRP combined with chemotherapy agent increased the rate of immunogenic cell death and prevented melanoma growth. Oncol Lett. 2017 Jul;14(1):844-852. doi: 10.3892/ol.2017.6202. Epub 2017 May 18. |
| 29298674 | Background | Martinez-Torres AC, Reyes-Ruiz A, Benitez-Londono M, Franco-Molina MA, Rodriguez-Padilla C. IMMUNEPOTENT CRP induces cell cycle arrest and caspase-independent regulated cell death in HeLa cells through reactive oxygen species production. BMC Cancer. 2018 Jan 3;18(1):13. doi: 10.1186/s12885-017-3954-5. |
| 31579619 | Background | Martinez-Torres AC, Gomez-Morales L, Martinez-Loria AB, Uscanga-Palomeque AC, Vazquez-Guillen JM, Rodriguez-Padilla C. Cytotoxic activity of IMMUNEPOTENT CRP against non-small cell lung cancer cell lines. PeerJ. 2019 Sep 27;7:e7759. doi: 10.7717/peerj.7759. eCollection 2019. |
| 32172064 | Background | Santana-Krimskaya SE, Franco-Molina MA, Zarate-Trivino DG, Prado-Garcia H, Zapata-Benavides P, Torres-Del-Muro F, Rodriguez-Padilla C. IMMUNEPOTENT CRP plus doxorubicin/cyclophosphamide chemotherapy remodel the tumor microenvironment in an air pouch triple-negative breast cancer murine model. Biomed Pharmacother. 2020 Jun;126:110062. doi: 10.1016/j.biopha.2020.110062. Epub 2020 Mar 12. |
| 32587616 | Background | Lorenzo-Anota HY, Martinez-Torres AC, Scott-Algara D, Tamez-Guerra RS, Rodriguez-Padilla C. Bovine Dialyzable Leukocyte Extract IMMUNEPOTENT-CRP Induces Selective ROS-Dependent Apoptosis in T-Acute Lymphoblastic Leukemia Cell Lines. J Oncol. 2020 Jun 8;2020:1598503. doi: 10.1155/2020/1598503. eCollection 2020. |
| 32660440 | Background | Martinez-Torres AC, Reyes-Ruiz A, Calvillo-Rodriguez KM, Alvarez-Valadez KM, Uscanga-Palomeque AC, Tamez-Guerra RS, Rodriguez-Padilla C. IMMUNEPOTENT CRP induces DAMPS release and ROS-dependent autophagosome formation in HeLa and MCF-7 cells. BMC Cancer. 2020 Jul 13;20(1):647. doi: 10.1186/s12885-020-07124-5. |
| 35381435 | Background | Lorenzo-Anota HY, Martinez-Loria AB, Tamez-Guerra RS, Scott-Algara D, Martinez-Torres AC, Rodriguez-Padilla C. Changes in the natural killer cell repertoire and function induced by the cancer immune adjuvant candidate IMMUNEPOTENT-CRP. Cell Immunol. 2022 Apr;374:104511. doi: 10.1016/j.cellimm.2022.104511. Epub 2022 Mar 26. |
| 36998710 | Background | Rivera-Lazarin AL, Martinez-Torres AC, de la Hoz-Camacho R, Guzman-Aguillon OL, Franco-Molinaa MA, Rodriguez-Padilla C. The bovine dialyzable leukocyte extract, immunepotent CRP, synergically enhances cyclophosphamide-induced breast cancer cell death, through a caspase-independent mechanism. EXCLI J. 2023 Jan 13;22:131-145. doi: 10.17179/excli2022-5389. eCollection 2023. |
| 39063180 | Background | Rivera-Lazarin AL, Calvillo-Rodriguez KM, Izaguirre-Rodriguez M, Vazquez-Guillen JM, Martinez-Torres AC, Rodriguez-Padilla C. Synergistic Enhancement of Chemotherapy-Induced Cell Death and Antitumor Efficacy against Tumoral T-Cell Lymphoblasts by IMMUNEPOTENT CRP. Int J Mol Sci. 2024 Jul 20;25(14):7938. doi: 10.3390/ijms25147938. |
| 22993557 | Background | Lara HH, Turrent LI, Garza-Trevino EN, Tamez-Guerra R, Rodriguez-Padilla C. Clinical and immunological assessment in breast cancer patients receiving anticancer therapy and bovine dialyzable leukocyte extract as an adjuvant. Exp Ther Med. 2010 May;1(3):425-431. doi: 10.3892/etm_00000066. Epub 2010 May 1. |
| 17573613 | Background | Franco-Molina MA, Mendoza-Gamboa E, Castillo-Tello P, Isaza-Brando CE, Garcia ME, Castillo-Leon L, Tamez-Guerra RS, Rodriguez-Padilla C. Bovine dialyzable leukocyte extract modulates cytokines and nitric oxide production in lipopolysaccharide-stimulated human blood cells. Cytotherapy. 2007;9(4):379-85. doi: 10.1080/14653240701320262. |
| 15857204 | Background | Franco-Molina MA, Mendoza-Gamboa E, Castillo-Leon L, Tamez-Guerra RS, Rodriguez-Padilla C. Bovine dialyzable leukocyte extract modulates the nitric oxide and pro-inflammatory cytokine production in lipopolysaccharide-stimulated murine peritoneal macrophages in vitro. J Med Food. 2005 Spring;8(1):20-6. doi: 10.1089/jmf.2005.8.20. |
| 18821359 | Background | Franco-Molina MA, Mendoza-Gamboa E, Zapata-Benavides P, Vera-Garcia ME, Castillo-Tello P, Garcia de la Fuente A, Mendoza RD, Garza RG, Tamez-Guerra RS, Rodriguez-Padilla C. IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a phase I study in non-small cell lung cancer patients. Cytotherapy. 2008;10(5):490-6. doi: 10.1080/14653240802165681. |
| 33531687 | Background | Reyes-Ruiz A, Calvillo-Rodriguez KM, Martinez-Torres AC, Rodriguez-Padilla C. The bovine dialysable leukocyte extract IMMUNEPOTENT CRP induces immunogenic cell death in breast cancer cells leading to long-term antitumour memory. Br J Cancer. 2021 Apr;124(8):1398-1410. doi: 10.1038/s41416-020-01256-y. Epub 2021 Feb 3. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |