Clinical trial NCT04342728: Coronavirus 2019 (COVID-19)- Using Ascorbic Acid and Zinc Supplementation
Official title: Coronavirus Disease 2019- Using Ascorbic Acid and Zinc Supplementation (COVIDAtoZ) Research Study A Randomized, Open Label Single Center Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID
Corona Virus Infection
Keywords: COVID-19
Viral Infection
Infection
Coronavirus-19
Ascorbic Acid
Zinc Gluconate
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2020-04-13
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: A single-center, prospective, open label four arm study (1. Zinc only 2. Zinc and ascorbic acid 3. Ascorbic acid only 4. Standard of care.
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to examine the impact of ascorbic acid (vitamin c) and zinc gluconate in reducing duration of symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19). Patients above the age of 18 who present to the Cleveland Clinic outpatient testing and receive a positive test for COVID-19 will be invited to participate.

Detailed description: We aim to see whether ascorbic acid and zinc gluconate which has limited side effect profile and is readily available over the counter can decrease the duration of symptoms seen in patients with new diagnosis of COVID-2019. A secondary purpose is to see whether Zinc and/or Ascorbic acid supplementation can prevent progression of the severe manifestations of the disease including development of dyspnea and acute respiratory distress syndrome which may require hospitalization, mechanical ventilation, and or lead to death.

This is a single-center, prospective, randomized study which plans to enroll 520 patients with a principal diagnosis of COVID-2019, managed in an outpatient setting, who presented after being sent by a healthcare provider to get tested and receive a PCR (Polymerase Chain Reaction) -assay based confirmed diagnosis of the disease. All patients who agree to participate in the study will answer a baseline questionnaire about their symptoms at the time of inclusion. Patients will then be randomized to one of 4 study arms. Patients in Arm A (n=130) will receive vitamin C (to be taken divided over 2-3 times a day with meals), patients in Arm B (n=130) will receive zinc gluconate to be taken at bedtime, patients in Arm C (n=130) will receive both vitamin C (to be taken divided over 2-3 times a day with meals) and zinc gluconate (taken at bedtime). Patients in arms A, B and C will take study supplements daily for 10 days. Patients in Arm D (n=130) will not receive any of the study medications and continue on standard of care. Patients will then track their symptoms daily from day 0 to day 28 answering 12 basic questions on illness severity.They will stop filling out their daily questions once they reach reach the end of the 28 day study period or at time of hospitalization; whichever comes first . Study team members will call patients at days 7, 14, 21, and 28 of the study period to assess need for hospitalization, ER visit, or additional medications prescribed by a healthcare provider, and any side effects from the supplements that the patient could have experienced.

Eligibility criteria: Inclusion Criteria:

* Outpatients ≥ 18 years presenting to Cleveland Clinic Health System in Ohio and Florida who test positive for COVID-19 having any of the following symptoms

  1. Fever or chills
  2. Shortness of breath or difficulty breathing
  3. Cough
  4. Fatigue
  5. Muscle or body Aches
  6. Headache
  7. New loss of taste
  8. New loss of smell
  9. Congestion or runny nose
  10. Nausea
  11. Vomiting
  12. Diarrhea

Women of child bearing potential:

1. have had a menstrual period within the past 30 days, or
2. have had previous sterilization, or
3. are perimenopausal (less than 1 year) who have a negative pregnancy test, or
4. women of childbearing potential who do not meet the above and have a negative pregnancy test.

Exclusion Criteria:

* Patients who are found to be positive during hospitalization
* Patients who reside outside Ohio or Florida.
* Pregnant women:

  1. Current known pregnancy
  2. Positive pregnancy test (women of child bearing potential who have not had previous sterilization as defined as hysterectomy or tubal ligation)
* Women of childbearing potential who do not meet the above criteria, last menstrual period greater than 30 days and have a positive pregnancy test.
* Lactating Women
* End stage kidney disease
* Advanced liver disease awaiting transplant
* History of Calcium Oxalate kidney stones.

Primary outcomes:
measure: Symptom Reduction
timeFrame: 28 days
Secondary outcomes:
measure: Symptom Resolution: Fever
timeFrame: 28 days
measure: Symptom Resolution: Cough
timeFrame: 28 days
measure: Symptom Resolution: Shortness of Breath
timeFrame: 28 days
measure: Symptom Resolution: Fatigue
timeFrame: 28 days
measure: Symptom Resolution: Muscle/body aches
timeFrame: 28 days
measure: Symptom Resolution: Headache
timeFrame: 28 days
measure: Symptom Resolution: New loss of taste
timeFrame: 28 days
measure: Symptom Resolution: New loss of smell
timeFrame: 28 days
measure: Symptom Resolution: Congestion/ runny nose
timeFrame: 28 days
measure: Symptom Resolution: Nausea
timeFrame: 28 days
measure: Symptom Resolution: Vomiting
timeFrame: 28 days
measure: Symptom Resolution: Diarrhea
timeFrame: 28 days
measure: Day 5 Symptoms
timeFrame: 5 days
measure: Hospitalizations
timeFrame: 28 days
measure: Severity of Symptoms
timeFrame: 28 days
measure: Adjunctive Medications
timeFrame: 28 days
measure: Supplementation Side Effects
timeFrame: 28 days
Other outcomes:
Locations:
city: Weston
country: United States
facility: Cleveland Clinic
state: Florida
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Milind Desai, M. D.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Suma Thomas
role: PRINCIPAL_INVESTIGATOR
References:
citation: O'Byrne L, Webster KE, MacKeith S, Philpott C, Hopkins C, Burton MJ. Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev. 2022 Sep 5;9(9):CD013876. doi: 10.1002/14651858.CD013876.pub3.
citation: O'Byrne L, Webster KE, MacKeith S, Philpott C, Hopkins C, Burton MJ. Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev. 2021 Jul 22;7(7):CD013876. doi: 10.1002/14651858.CD013876.pub2.
citation: Thomas S, Patel D, Bittel B, Wolski K, Wang Q, Kumar A, Il'Giovine ZJ, Mehra R, McWilliams C, Nissen SE, Desai MY. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2021 Feb 1;4(2):e210369. doi: 10.1001/jamanetworkopen.2021.0369.