Pharmacologic Ascorbic Acid as an Activator of Lymphocyte Signaling for COVID-19 Treatment

COVID-19 Clinical Trial

Official title:

Pharmacologic Ascorbic Acid as an Activator of Lymphocyte Signaling for COVID-19 Treatment

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04363216
• Other study ID #: JT#15681
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 2020
• Est. completion date: May 2021

Study information

• Verified date: May 2020
• Source: Thomas Jefferson University
• Contact: Michael W Foster, M.D.
• Phone: 6107160962
• Email: mxf314[@]jefferson.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There are currently no approved therapies for patients with coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infusion of ascorbic acid (vitamin C) has been shown to increase activity of lymphocytes, which are a crucial component of the body's defense against viral disease progression and adaptive immunity. Ascorbic acid infusion has been shown to be a safe treatment for patients suffering from sepsis and certain types of cancer. This study is designed to evaluate the safety and efficacy of ascorbic acid in the form of sequential I.V. infusions (Ascor®) for patients with suspected COVID-19 who are unlikely to require mechanical ventilation within 24 hours of study intervention.

Description:

Ascorbic acid [AA] (vitamin C) is an essential nutrient that, in addition to aiding tissue repair, also functions as an enzyme co-factor, an antioxidant, and a key component in lymphocyte development and function. Lymphocytes are responsible for adaptive immunity, the immune response following vaccination, in addition to playing a vital role in protection against viral disease progression. Both sepsis and aberrant lymphocyte activation have been associated with severe AA deficiency. We hypothesize that the administration of increasing concentrations of pharmacologic AA promotes lymphocyte activation and signaling in newly admitted, non-ventilator dependent COVID-19 patients via hydrogen peroxide generation and/or DNA de-methylation, and that this will lead to improved clinical outcomes.

This is a single-center, prospective, randomized, open-label, phase II clinical trial designed to assess the efficacy, tolerability, and safety of pharmacologic AA administration in hospitalized patients newly-diagnosed with COVID-19 who will likely not require mechanical ventilation within 24 hours of study intervention. All subjects enrolled will be pending inpatient admission or already admitted as they will require supplemental oxygen. Within 12 hours of admission to the E.D. or medical/surgical floor (rapid screens to determine eligibility must be completed within this time), patients will receive escalating pharmacologic AA over 2 hours once daily for 3 escalating doses, then continued on the highest dose for a total of 6 infusions.

Subjects will be randomized 2:1, with 66 subjects receiving AA treatments and 22 subjects receiving routine clinical care. The open-label design allows investigators to evaluate the safety and clinical progress in real-time. Any subject randomized to AA treatment who is upgraded to ICU-level care, requires high-flow O2 supplementation, or is intubated, will no longer receive AA infusions in order to maximize patient safety during this study. Given the robust safety data on the treatment, a phase II design was chosen with an interim safety analysis after 21 patients. Randomization will be stratified according to high vs. low risk of complications. Patients will be considered to be high risk if they have any of the following characteristics: age>60, hypertension, structural lung disease, cardiovascular disease, diabetes, immunocompromising conditions or meds (such as immunosuppressing meds in transplant patients).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 66
• Est. completion date: May 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or non-pregnant female > 18 years of age at the time of consent

2. ConfirmedSARS-CoV-2 infection

3. Disease severity necessitating hospitalization

4. Currently taking supplemental oxygen

5. No anticipated need (within 24 hours) for mechanical ventilation, defined as:

1. Positive clinical response to oxygen supplementation with improvement in hypoxia or

2. Hypoxia improvement with bronchospasm therapy if bronchospasm present

Exclusion Criteria

1. eGFR < 50

2. Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency

3. Anticipated need for mechanical ventilation within 24 hours

4. Pregnant or breastfeeding

5. Requires home oxygen for any reason

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Ascorbic Acid
Ascor® ascorbic acid 2-hour infusion daily (for 6 days), escalating dose (0.3g/kg, 0.6g/kg, 0.9g/kg).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Thomas Jefferson University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Improvement	• Clinical improvement at 72 hours of treatment, defined as a 50% reduction in the highest flow rate of oxygen during the 72 hour period, a 50% reduction in the most frequent use of bronchodilators within a 12-hour window within the 72-hour period, or hospital discharge (whichever comes first).	72 hours
Secondary	Patient status upgraded to ICU level [Clinical decline]	Subject is upgraded to ICU-level care	36 hours
Secondary	Oxygen supplementation	Overall rate of oxygen supplementation in L/min	up to 1 year
Secondary	Days with fever	Number of days during hospitalization where a fever (>100.4°F) is reached at least once	up to 1 year
Secondary	Days to discharge	Number of days from initial treatment to hospital discharge	up to 1 year
Secondary	SAEs	Serious adverse events specific to treatment	up to 1 year