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COVID-19Phase 1/2ICRPDLECOVIDNCT06676709

Effect of IMMUNEPOTENT-CRP on Serum Pro-Inflammatory Cytokines in Mild to Moderate COVID-19

A Phase 1/2 study testing IMMUNEPOTENT-CRP (I-CRP) in people with COVID-19 and SARS-CoV2 Infection, run by Universidad Autonoma de Nuevo Leon at 2 sites in Mexico.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19, SARS-CoV2 Infection
What is being tested?
IMMUNEPOTENT-CRP (I-CRP)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
2 sitesMexico
Study dates
20 Apr 2021to 5 Mar 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Outpatients Inclusion Criteria:

  • Laboratory-confirmed SARS-CoV-2 infection (by antigen or RT-qPCR test).
  • With mild to moderate symptoms of COVID-19.
  • Aged ≥ 18 years.
  • Not participating in any other clinical study.
  • Written informed consent duly signed.

Outpatients Exclusion Criteria:

  • Undergoing any process of primary or secondary immunosuppression.
  • Any autoimmune disease.
  • Receiving chemotherapy.
  • History of lymphoma or any malignancy.
  • Pregnancy or breastfeeding women.

Trial locations and contacts

2 sites in 1 country.

Mexico2 sites

  • Hospital Universitario "Dr. Jose E. Gonzalez", Universidad Autonoma de Nuevo Leon

    Monterrey, Nuevo León, 64460

  • Laboratorio de Inmunologia y Virologia

    San Nicolás de los Garza, Nuevo León, 66450

Other trials in Mexico

About this study

Official title: Effect of IMMUNEPOTENT-CRP, a Bovine Dialyzable Leukocyte Extract, on Serum Pro-Inflammatory Cytokines in Outpatients with Mild to Moderate COVID-19: a Randomized, Double-Blind, Placebo-Controlled Study

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.

Read the detailed description

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.

Being tested
IMMUNEPOTENT-CRP (I-CRP), Placebo Comparator
Keywords
Cytokine storm, Mild to moderate COVID-19, Inflammatory cytokines, Dialyzable Leukocyte Extract (DLE), IMMUNEPOTENT-CRP (I-CRP)
Medical subject headings
COVID-19, Cytokine Release Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IMMUNEPOTENT-CRP (I-CRP)Biological

    Also called Bovine Dialyzable Leukocyte Extract (DLE)

    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.

  • Placebo ComparatorBiological

    The placebo was prepared from a lyophilized corn starch extract and was provided in an identical appearance and presentation to IMMUNEPOTENT-CRP (I-CRP).

Study groups in NCT06676709
Study groupRoleWhat they receive
I-CRP groupExperimentalIMMUNEPOTENT-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.
Receives: Biological: IMMUNEPOTENT-CRP (I-CRP)
Placebo controlPlacebo comparatorThe 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.
Receives: Biological: Placebo Comparator

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Assessments were performed at baseline (Day 0), and during the intervention period at Day 7 and Day 14.

Secondary outcomes (6)

  1. Lactate Dehydrogenase (LDH) Levels

    Plasma levels of lactate dehydrogenase (LDH) were measured using standard biochemistry tests. Reference normal values are 230-460 mg/dL.

    Measured: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.

  2. High-Sensitivity C-Reactive Protein (hs-CRP) Levels

    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.

    Measured: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.

  3. Ferritin Levels

    Serum levels of ferritin were measured using standard biochemistry tests. Reference normal values are 13-150 ng/mL.

    Measured: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.

  4. D-Dimer Levels

    Plasma levels of D-dimer were measured using standard biochemistry tests. Reference normal values are 0.0-0.5 μg/mL.

    Measured: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.

  5. 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 FACSCanto™ flow cytometer (BD Biosciences).

    Measured: 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.

  6. 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.

    Measured: SARS-CoV-2 infection status was evaluated at baseline (Day 0), Day 7, Day 14, and Day 30 during outpatient follow-up.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2024
  2. Study start20 Apr 2021
  3. Primary completion3 Feb 2022
  4. Study completion5 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06676709
Sponsor's protocol ID
EN21-00050/LIVFCB-2021-001
Other IDs
EN21-00050
Acronym
ICRPDLECOVID
Status last verified
Nov 2024
First submitted
29 Oct 2024
Last updated
8 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The individual participant data (IPD) to be shared with other researchers will include the following variables related to the study participants: * Basic demographic information (such age, sex, and others) * Serum levels of pro-inflammatory cytokines * Relevant clinical data related to SARS-CoV-2 infection, such as symptom severity and clinical progression * Data on treatment group allocation (IMMUNEPOTENT-CRP or placebo) 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.

Publications

  • Franco-Molina MA, Santana-Krímskaya SE, Zarate-Triviño DG, Zapata-Benavides P, Hernández-Martínez 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.

  • 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.

    PubMed 31013404

  • 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.

    PubMed 15454111

  • 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.

    PubMed 16997795

  • 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.

    PubMed 16923617

  • 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.

    PubMed 18368600

  • 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.

    PubMed 20205507

  • 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.

    PubMed 22044844

  • 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.

    PubMed 28101208

  • 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.

    PubMed 37223080

  • 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.

    PubMed 37240318

  • 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.

    PubMed 38077402

  • 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.

    PubMed 27191003

  • 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.

    PubMed 28693241

  • 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.

    PubMed 29298674

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IMMUNEPOTENT-CRP (I-CRP) in people with COVID-19 and SARS-CoV2 Infection, run by Universidad Autonoma de Nuevo Leon at 2 sites in Mexico.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cytokine and Chemokine Serum Levels Evaluation (time frame: Assessments were performed at baseline (Day 0), and during the intervention period at Day 7 and Day 14.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06676709, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2024.

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