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

November 5, 2024 updated by: Dr. Jose Manuel Vazquez-Guillen, Universidad Autonoma de Nuevo Leon

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64460
        • Hospital Universitario "Dr. Jose E. Gonzalez", Universidad Autonoma de Nuevo Leon
      • San Nicolas de los Garza, Nuevo Leon, Mexico, 66450
        • Laboratorio de Inmunologia y Virologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: I-CRP group
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.
Biological: IMMUNEPOTENT-CRP (I-CRP)
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.
Other Names:
  • Bovine Dialyzable Leukocyte Extract (DLE)
Placebo Comparator: Placebo control
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.
Biological: 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lactate Dehydrogenase (LDH) Levels
Time Frame: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.
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
Time Frame: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.
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
Time Frame: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.
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
Time Frame: Measurements were taken at baseline (Day 0), Day 7, and Day 14 during the intervention period.
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
Time Frame: 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.
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).
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
Time Frame: SARS-CoV-2 infection status was evaluated at baseline (Day 0), Day 7, Day 14, and Day 30 during outpatient follow-up.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Autonoma de Nuevo Leon

Collaborators

Hospital Universitario Dr. Jose E. Gonzalez
Laboratorio de Inmunologia y Virologia - UANL

Investigators

  • Study Director: Cristina Rodriguez-Padilla, Ph.D., Universidad Autonoma de Nuevo Leon
  • Study Chair: Rene Rodriguez-Gutierrez, Ph.D., Universidad Autonoma de Nuevo Leon
  • Principal Investigator: Jose Manuel Vazquez-Guillen, Ph.D., Universidad Autonoma de Nuevo Leon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 20, 2021

Primary Completion (Actual)

February 3, 2022

Study Completion (Actual)

March 5, 2022

Study Registration Dates

First Submitted

October 29, 2024

First Submitted That Met QC Criteria

November 4, 2024

First Posted (Actual)

November 6, 2024

Study Record Updates

Last Update Posted (Estimated)

November 8, 2024

Last Update Submitted That Met QC Criteria

November 5, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EN21-00050/LIVFCB-2021-001
  • EN21-00050 (Other Identifier: Universidad Autónoma de Nuevo León)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

The data will be available for a period of 3 years following the publication of the study.

IPD Sharing Access Criteria

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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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