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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04517162
Recruitment Status : Recruiting
First Posted : August 18, 2020
Last Update Posted : September 3, 2020
Sponsor:
Information provided by (Responsible Party):
Janette Furuzawa Carballeda, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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.


Condition or disease Intervention/treatment Phase
Covid19 Cytokine Storm Regulation of Inflammatory Response Pulmonary Fibrosis Drug: Collagen-Polyvinylpyrrolidone Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double Blind Placebo-controlled Clinical Trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Collagen-Polyvinylpyrrolidone for the Treatment of Hyperinflammation and the Pulmonary Fibrosis in COVID-19 Patients. Double Blind Placebo-controlled Pilot Trial
Actual Study Start Date : August 19, 2020
Estimated Primary Completion Date : February 19, 2021
Estimated Study Completion Date : June 19, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active comparator or polymerized type I collagen
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
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)
Other Names:
  • Fibroquel
  • Polymerized-Type I Collagen
  • polymerized type I collagen

Placebo Comparator: Placebo comparator o placebo
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
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)
Other Names:
  • Fibroquel
  • Polymerized-Type I Collagen
  • polymerized type I collagen




Primary Outcome Measures :
  1. Clinical primary Outcome measure [ Time Frame: 14 days ]

    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.


Secondary Outcome Measures :
  1. Immunological secondary outcome measure [ Time Frame: 3 months ]

    It will be considered as secondary outcome if the patients meet the first criterion, or 2 of the remaining 3:

    1. significant decrease in serum IP-10 (at least 30% compared to placebo and baseline), since this chemokine is directly associated with the progression and severity of COVID-19,
    2. significant decrease in serum pro-inflammatory cytokines (TNF-a, IL-1β, IL-7, at least 30% compared to placebo and baseline),
    3. significant decrease in the percentage of circulating effector T cells (at least 30% compared to placebo and baseline), or
    4. significant improvement from computerized axial tomography at re-examination. This improvement is defined as: a decrease of at least 40% in parenchymal attenuation, the appearance of ground glass, nodular opacities, thickening of interlobular septa and / or thickening of bronchial walls.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04517162


Contacts
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Contact: Janette Furuzawa-Carballeda, PhD +525554850766 jfuruzawa@gmail.com
Contact: Enrique Ochoa-Hein, MD +525554870900 ext 7901-7906 jfuruzawa@gmail.com

Locations
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Mexico
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Recruiting
Mexico, Cdmx, Mexico, 14080
Contact: Janette Furuzawa-Carballeda, PhD    5536777923    jfuruzawa@gmail.com   
Contact: Eric Ochoa-Hein, MD    5554870900 ext 7901    dr_eric_ochoa@yahoo.com.mx   
Sponsors and Collaborators
Janette Furuzawa Carballeda
Investigators
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Principal Investigator: Eric Ochoa-Hein, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Chair: Luis A Septien-Stute, MD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Director: Janette Furuzawa-Carballeda, PhD Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Chair: 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
Additional Information:
Publications of Results:

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Responsible Party: Janette Furuzawa Carballeda, Medical science resercher, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
ClinicalTrials.gov Identifier: NCT04517162    
Other Study ID Numbers: IRE-3412-20-21-1
First Posted: August 18, 2020    Key Record Dates
Last Update Posted: September 3, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Data will be provided based on requirement

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Povidone
Plasma Substitutes
Blood Substitutes