Metabolic Cofactor Supplementation and Hydroxychloroquine Combination in Covid-19 Patients

A Multi Centre, Randomised, Controlled, Open-Label Phase 2/3 Study to Evaluate the Efficacy, Tolerability and Safety of Metabolic Cofactor Supplementation and Hydroxychloroquine Combination in Covid-19 Patients

This open label, randomized, controlled, investigator-initiated, multi-centre trial aims to establish metabolic improvements in COVID-19 subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine plus standard therapy. The primary objective is to assess the clinical efficacy of the combination of metabolic cofactors supplementation and hydroxychloroquine in COVID-19 patients.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Hydroxychloroquine + Metabolic cofactor supplementation; Drug: Hydroxychloroquine + Sorbitol

Detailed Description

Coronaviruses are a large family of ribonucleic acid viruses that cause mild to moderate upper respiratory diseases in humans. There is an urgent need for COVID-19 therapeutics due to the S-shaped curve expansion of the infections, widespread pandemic status, and global burden. Given the similarities between SARS-CoV-2 and other coronaviruses, and its relative ease of sample acquisition and study, it has been widely accepted that drug repositioning is a promising approach to make available an effective, safety-assured treatment in a timely manner.

This open label, randomized, controlled, investigator-initiated, multi-centre trial aims to establish metabolic improvements in COVID-19 subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine plus standard therapy. The investigational drug products, the mixture of the four co-factors will be administered as a powder with strawberry aroma to be dissolved in 200 ml of preferably cold still drinking water and be consumed within 5 minutes.

This study is planned as a Phase II / III clinical drug research to be conducted in patients diagnosed with COVID-19. Patients will be ambulatory and after the diagnosis/confirmation of diagnosis, will be sent home with their treatment. However, patients may be hospitalised during this initial examination period due to deterioration in their physical health or due to any medical condition which was not present at admission.

The primary objective is to assess the clinical efficacy of the combination of metabolic cofactors supplementation and hydroxychloroquine in COVID-19 patients. For the primary purpose, the proportion of patients who were hospitalised during the course of disease until 14 days after the initial diagnosis of Covid-19 disease will be compared. Patients who were hospitalised during the 14-day period, but at any time point after consenting will be evaluated as an end-point occurrence.

The secondary aim in this study is to evaluate the safety and tolerability of metabolic cofactors supplementation and hydroxychloroquine combination.

The initial part of the Phase II/III study is planned as a Phase II study which will enrol 100 patients and after an interim analysis it will conclude as a Phase III study (300 patients). Totally 400 COVID-19 disease patients will be randomized on a 3:1 basis to the combination metabolic cofactors supplementation and hydroxychloroquine or hydroxychloroquine+ placebo in eight clinical sites in Turkey.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey
    • University of Health Sciences Istanbul Ümraniye Training and Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients of both genders (females and males) over 18 years of age
• Written informed consent obtained from the subjects prior to any procedures related to the study
• Understand all procedures to be applied within the scope of the study protocol
• Ambulatory patients with symptoms diagnosed with COVID-19 with Chest tomography (CT) result positivity in the last 72 hours
• Patients with stable clinical course and who could be treated on an ambulatory basis.

Exclusion Criteria:

• Patients who has partial oxygen saturation below 93% and require immediate hospitalisation after diagnosis
• Patients, upon initial examination, decided to be hospitalised at the intensive care-unit
• Inability or unwillingness to give written informed consent
• At physicians decision, the trial involvement will not be in patients' best interest, or any condition that does not allow the protocol to be followed safely
• Patients considered as inappropriate for this study for any reason
• Active participation in another clinical study
• Uncontrolled Type 1 or type 2 diabetes
• Severe liver disease (e.g. Child Pugh score ≥ C, AST>5 times upper limit)
• Patients with known severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis
• Significant cardiovascular co-morbidity (i.e. heart failure)
• Patients with phenylketonuria (contraindicated for NAC)
• Known allergy for substances used in the study
• Pregnant or breastfeeding patients, or patients with positive pregnancy test in a pre-dose examination
• Receipt of any experimental treatment for COVID-19 within the 30 days prior to the time of the screening evaluation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Subjects in ambulatory-at home-treatment will receive hydroxychloroquine (standard therapy) + dietary supplement consisting of serine, L-carnitine tartrate, N-acetylcysteine and nicotinamide riboside.	Drug: Hydroxychloroquine + Metabolic cofactor supplementation; Treatment arm will include dietary supplement consisting of serine, L-carnitine tartrate, N-acetylcysteine and nicotinamide riboside + standard therapy (hydroxychloroquine).
Placebo Comparator: Placebo Arm; Subjects will take hydroxychloroquine (standard therapy) + dietary supplement placebo.	Drug: Hydroxychloroquine + Sorbitol; Placebo comparator will include sorbitol as placebo + standard therapy (hydroxychloroquine).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The evaluation of clinical efficacy of the combination of metabolic cofactor supplementation and hydroxychloroquine	The clinical efficacy will be evaluated by comparing the proportion of patients who were hospitalised during the course of disease until 14 days after the initial diagnosis of Covid-19.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in alanine aminotransferase (ALT) levels from baseline	Clinical evaluation of ALT levels from baseline until the end of study.	14 days
Changes in aspartate aminotransferase (AST) levels from baseline	Clinical evaluation of AST levels from baseline until the end of study.	14 days
Changes in C-reactive protein (CRP) levels from baseline	Clinical evaluation of CRP levels from baseline until the end of study.	14 days
Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment	Number/characteristics of Adverse Event (AE), Serious Adverse Event (SAE) and discontinuation of treatment due to study drug from baseline until the end of study.	14 days
Chest Tomography	Chest imaging will be documented at baseline visit.	1 day
ECG Measurement	Change in heart rate will be measured at baseline visit.	1 day
Change of complete blood count from baseline	Complete blood count includes number of blood cells and concentration of hemoglobin. Complete blood count will be performed to measure possible toxic effects of the metabolic cofactors supplementation and hydroxychloroquine combination on hematological system.	14 days
Changes in creatinine levels from baseline	Clinical evaluation of creatinine levels from baseline until the end of study.	14 days
Changes in D-dimer levels from baseline	Clinical evaluation of D-dimer levels from baseline until the end of study.	14 days
Changes in ferritin levels from baseline	Clinical evaluation of ferritin levels from baseline until the end of study.	14 days
Changes in triglycerides levels from baseline	Clinical evaluation of triglycerides levels from baseline until the end of study.	14 days
Changes in LDH levels from baseline	Clinical evaluation of LDH levels from baseline until the end of study.	14 days

Collaborators and Investigators

• Sponsor: ScandiBio Therapeutics AB
• Collaborators: Bakirkoy Dr. Sadi Konuk Research and Training Hospital; Kanuni Sultan Suleyman Training and Research Hospital; Bagcilar Training and Research Hospital; Istanbul Medipol University Hospital; Monitor CRO; Istanbul Umraniye Training and Research Hospital; Dr. Lutfi Kirdar Kartal Training and Research Hospital; Alanya Alaaddin Keykubat University Alanya Training and Research Hospital; Canakkale 18 Mart University Health Research and Application Hospital
• Investigators: Principal Investigator: Assoc. Prof. Levent DOĞANAY, MD, University of Health Sciences Istanbul Ümraniye Training and Research Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): May 5, 2022
• Study Completion (Actual): May 5, 2022

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Cathartics; Hydroxychloroquine; Sorbitol
• Other Study ID Numbers: COVID-19-MCS

Drug and device information, study documents

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