"CHANGE COVID-19 Severity" (CHANGE)

Investigation of Choice Alteration of the Gut Metagenome on COVID-19 Severity

We are conducting an investigator-initiated, single center, blinded, placebo-controlled, randomized clinical trial evaluating magnesium citrate combined with a probiotic for the treatment of adults hospitalized with COVID-19.

Study Overview

• Status: Terminated
• Conditions: COVID-19 Infection
• Intervention / Treatment: Drug: Magnesium Citrate plus probiotic

Detailed Description

We are conducting an investigator-initiated, single center, blinded, placebo-controlled, randomized clinical trial evaluating magnesium citrate combined with a probiotic for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.

This research study is being done to determine if taking oral magnesium citrate and a probiotic will improve the outcome of adults hospitalized with COVID-19. In this study, half of the participants will receive magnesium citrate plus a probiotic and half will receive a placebo randomized 1:1. You will be placed in one of these 2 groups randomly, like the flip of a coin. The investigational arm will receive one 10 oz. bottle of magnesium citrate to drink once and 2 oral probiotic capsules to be taken twice a day for 6 days. We will also collect a blood sample on Day 1 and Day 7 for CD4+ and CD8+ evaluation and will be collecting data on each participants COVID-19 infection progression during hospitalization.

Assessments for this study will be done on day 7 and day 29 if the participant is still hospitalized at those time points. If they have been discharged from the hospital before these assessments, we will do these by phone. Each participant will also be contacted at 3 months to assess how they are doing. There will be no compensation for taking part in this study.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years
2. Currently hospitalized or in an emergency department with anticipated hospitalization.

3. Symptoms of acute respiratory infection, defined as one or more of the following:

   1. Cough
   2. Fever (> 37.5° C / 99.5° F)
   3. Shortness of breath (operationalized as any of the following: subjective shortness of breath reported by patient or surrogate; tachypnea with respiratory rate ≥22 /minute; hypoxemia, defined as SpO2 <92% on room air, new receipt of supplemental oxygen to maintain SpO2 ≥92%, or increased supplemental oxygen to maintain SpO2 ≥92% for a patient on chronic oxygen therapy).
   4. Sore throat
   5. Anosmia
4. Laboratory-confirmed SARS (Severe acute respiratory syndrome-Coronavirus 2 (SARS CoV-2) infection within 10 days prior to randomization
5. Ability to manage own stool care

Exclusion Criteria:

1. Prisoner
2. Pregnancy
3. Breast feeding
4. Current infectious or noninfectious diarrheal illness
5. Unable to randomize within 21 days after onset of acute respiratory infection symptoms
6. Unable to randomize after hospital arrival
7. Colonic obstruction
8. Unresolved hypovolemia
9. CrCl <30ml/min
10. Hypermagnesemia
11. Diagnosis of Long QT syndrome
12. Known allergy to magnesium citrate or probiotic
13. Unresolved electrolyte imbalance such as hypokalemia or hypocalcemia. The patient can be enrolled if electrolytes are corrected and sustained.
14. Receipt of >1 dose of magnesium citrate or any other colonic cleanser in the 7 days prior to enrollment
15. Inability to receive enteral medications
16. Refusal or inability to be contacted on Day 15 for clinical outcome assessment if discharged prior to Day 15
17. Concurrent medical illness that interferes with clinical assessment Previous enrollment in this trial
18. The treating clinical team does not believe equipoise exists regarding the use of magnesium citrate plus a probiotic for the treatment of this patient.
19. Participating in any other COVID-19 therapeutic trial
20. Allergic to soy.
21. Lactose intolerant.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnesium Citrate plus a Probiotic Arm: Participants assigned to the magnesium citrate plus a probiotic arm will receive 1 bottle of magnesium citrate 296 mL PO once to be taken within a 4-hour period, (about 10 oz.). Because magnesium citrate remains within the intestinal lumen, a second bottle can be provided if there is limited bowel movement. Patients will be asked to take 2 capsules of probiotics twice daily for six days or until discharge, whichever is earlier.	Drug: Magnesium Citrate plus probiotic; 296 ml magnesium citrate
Placebo Comparator: Placebo; Participants randomized to the placebo arm will receive matching placebo 296 mL PO once to be taken within a 4-hour period, (about 10 oz.) and 2 cellulose capsules twice daily for six days or until discharge, whichever is earlier. The placebo will be flavored to match the taste of the interventional arm.	Drug: Magnesium Citrate plus probiotic; 296 ml magnesium citrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in COVID Ordinal Outcome Scale	Scoring Criteria 0 = Uninfected, no viral RNA detected; = Asymptomatic, viral RNA detected; = Symptomatic, independent; = Symptomatic, assistance needed; = Hospitalized, no oxygen needed; = Hospitalized, oxygen by mask or nasal prongs; = Hospitalized, oxygen by NIV or high flow; = Intubation and mechanical ventilation, pO2/FiO2 ≥150 or SpO2/FiO2 ≥200; = Mechanical ventilation, pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors; = Mechanical ventilation, pO2/FiO2 <150 and vasopressors, dialysis or ECMO; = Dead	Baseline through Day 7 after completion of therapy

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): November 4, 2021
• Primary Completion (Actual): June 25, 2022
• Study Completion (Actual): June 25, 2022

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): November 17, 2022
• Last Update Submitted That Met QC Criteria: November 11, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Gastrointestinal Agents; Cathartics; Magnesium citrate
• Other Study ID Numbers: 210598

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes