Intramuscular Effect of Polymerized Type I Collagen on the Cytokine Storm in COVID-19 Patients

NCT04517162 | Unknown Phase 1 DMC

• 1 other identifier: IRE-3412-20-21-1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

SARS-CoV-2 infection induces a hyperinflammatory syndrome, causing the acute respiratory distress syndrome, massive lung cell destruction and, as a plausible sequelae, pulmonary fibrosis in COVID-19 patients. Current focus has been on the development of novel immunosuppressant therapies, in order to control the cytokine storm in COVID-19 patients. Thus, the effect of steroids, intravenous immunoglobulin, non-steroidal immunosuppressants, selective cytokine blockade, JAK/STAT pathway inbhibition, and mesenchymal precursor cells have been evaluated. Based on the above information, we propose COLLAGEN-POLYVINYLPYRROLIDONE (Distinctive name: FibroquelMR, active substance: Collagen-polyvinylpyrrolidone, pharmaceutical form: intramuscular injectable solution, with sanitary registration No. 201M95 SSA IV and SSA code: 010 000 3999) as a potential drug for the downregulation of the cytokine storm. Polymerized type I collagen reduces the expression of IL-1β, IL-8, TNF-alpha, TGF-β1, IL-17, Cox-1, leukocyte adhesion molecules (ELAM-1, VCAM- 1 and ICAM-1), some other mediators of inflammation and increases the levels of IL-10 and the number of regulatory T cells. In addition, it promotes the mechanisms of inhibition of tissue fibrosis, without adverse effects in rheumatoid arthritis and osteoarthritis.

Conditions

Covid19; Cytokine Storm; Regulation of Inflammatory Response; Pulmonary Fibrosis

Outcome Measures

Primary Outcomes (1)

• Clinical primary Outcome measure

  It will be considered as primary outcome if the patients meet the first criterion, or 2 of the remaining 3: 1. No oxygen required to maintain oxygen saturation more than 92%, 2. Decrease in severity category from Table 1 by at least 1 level, or 3. Reduction in the time of symptoms, by at least 30% compared to placebo and baseline, or 4. recovery of at least 30% the number of lymphocytes compared to placebo and baseline.

  14 days

Secondary Outcomes (1)

• Immunological secondary outcome measure

  3 months

Study Arms (2)

Active comparator or polymerized type I collagen

ACTIVE COMPARATOR

1.5 mL of polymerized type I collagen every 12 h for 3 days and then every 24 h for 4 days (in total 10 injections in 7 days)

Drug: Collagen-Polyvinylpyrrolidone

Placebo comparator o placebo

PLACEBO COMPARATOR

1.5 mL of placebo, every 12 h for 3 days and then every 24 h for 4 days (in total 10 injections in 7 days)

Drug: Collagen-Polyvinylpyrrolidone

Interventions

Collagen-Polyvinylpyrrolidone DRUG

1.5 mL of polymerized-type I collagen or placebo, every 12 h for 3 days and then every 24 h for 4 days (in total 10 injections in 7 days)

Also known as: Fibroquel, Polymerized-Type I Collagen, polymerized type I collagen

Active comparator or polymerized type I collagen; Placebo comparator o placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• According to the sample size calculation (Cohen's d calculation, using a 50% decrease in IP-10 as the expected effect size), 90 COVID-19 patients will be recruited (symptoms: cough, expectoration, odynophagia, dyspnea with or without fever; radiographic findings by imaging study: inflammatory infiltrates), of both sexes, older than 18 years.
• Participants will be enrolled, even when they do not have a laboratory-confirmed SARS-CoV-2 infection as determined by a positive reverse transcription, polymerase-chain-reaction (RT-PCR) assay result. Patients will be included if they have progressive disease consistent with ongoing SARS-CoV -2 infection.
• Patients with laboratory predictors of mild to severe disease (D-dimer\> 1000 ng/ml; total lymphocytes \<800 cells/µl, creatine phosphokinase\> 2 times upper limit of the normal range; elevated troponins and ferritin\> 300 µg/L) will be included.
• Only those patients who are negative to the intradermal reaction of polymerized type I collagen (subcutaneous application of 0.2 ml of the drug on the forearm, evaluation at 24-48h) will be included.
• Patients with mild to severe disease, peripheral oxygen saturation (SpO2) \<92% on room air, or requiring supplemental oxygen, or mechanical ventilation will be recruited. There will be no limit to the duration of symptoms prior to enrollment.
• Only those patients who are not participating in another protocol and who are not receiving biological therapy and whose standardized therapy is suggested will be included (AmoxiClav or ceftriaxone, or azithromycin, clarithromycin or doxycycline, ivermectin, low molecular weight anticoagulants, paracetamol).
• All patients who agree to participate in the protocol and from whom written informed consent is obtained will be included.

You may not qualify if:

• All patients positive for intradermal reaction to polymerized type I collagen (allergy to study producto) will be excluded.
• All pregnant or breast-feeding patients, patients with chronic kidney disease as determined by calculating an estimated glomerular filtration rate (eGFR), or need for hemodialysis or hemofiltration, patients with cerebrovascular disease, autoimmune disease, cancer, multiorgan failure or immunodeficiencies (HIV, transplant patients, hematological diseases, patients with chemotherapy) will be excluded.

Sponsors & Collaborators

• Janette Furuzawa Carballeda: lead

Study Sites (1)

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

Mexico City, Mexico City, 14080, Mexico

RECRUITING

Related Publications (31)

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Related Links

• Polymerized-Type I collagen induces a high-quality cartilage repair in a rat model of osteoarthritis
• Correlation Analysis Between Disease Severity and Inflammation related Parameters in Patients with COVID-19 Pneumonia
• . Successful Treatment Strategy of Turkey against Covid-19 Outbreak
• Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP).
• Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome

MeSH Terms

Conditions

COVID-19; Cytokine Release Syndrome; Pulmonary Fibrosis

Interventions

collagen-PVP

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Lung Diseases, Interstitial; Fibrosis

Study Officials

• Eric Ochoa-Hein, MD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  PRINCIPAL INVESTIGATOR

• Luis A Septien-Stute, MD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY CHAIR

• Janette Furuzawa-Carballeda, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY DIRECTOR

• Gonzalo Torres-Villalobos, MD, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY CHAIR

• Daniel Azamar-Llamas, MD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY CHAIR

• Diego F Hernández-Ramírez, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY CHAIR

• Elizabeth Olivares-Martínez, PhD

  Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

  STUDY CHAIR

Central Study Contacts

Janette Furuzawa-Carballeda, PhD

CONTACT

+525554850766; jfuruzawa@gmail.com

Enrique Ochoa-Hein, MD

CONTACT

+525554870900; jfuruzawa@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical science resercher

Model Details: Double Blind Placebo-controlled Clinical Trial

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: August 18, 2020
• Study Start: August 19, 2020
• Primary Completion: February 19, 2021
• Study Completion: June 19, 2021
• Last Updated: February 17, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)