Coenzyme Q10 as Treatment for Long Term COVID-19 (QVID)

This study is a randomized, placebo-controlled, double-blinded, cross-over designed clinical trial investigating the effect of high-dose Coenzyme Q10 treatment in subjects with persisting symptoms more than 12 weeks af SARS-CoV-2 infection, Long Term COVID-19 (LTC).

Study Overview

• Status: Completed
• Conditions: Covid19; Long Term Covid19
• Intervention / Treatment: Drug: Coenzyme Q10; Drug: Placebo

Detailed Description

The aim is to investigate the effect of high-dose Coenzyme Q10 on number and severity of self-reported symptoms in patients with Long Term COVID-19.

The study will be conducted at the Department of Infectious Diseases, Aarhus University Hospital in the LTC Outpatient Clinic. 120 study participants will be randomized 1:1 to receive placebo or CoQ10 in a dose of 500mg/day for 6 weeks. After a wash-out period of 4 weeks, participants are allocated to the opposite treatment for 6 weeks. The EQ-5D-5L and an LTC-specific questionnaire are completed at baseline and after 6,10,16, and 20 weeks. At each of 5 visits blood samples will be collected from the participants for immunological investigations and assessment of cellular metabolism.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N
    • Aarhus, Aarhus N, Denmark, 8200
      • Department of Infectious Diseases

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age above 18 years.
• Able to give informed consent.
• History of documented SARS-CoV-2 infection either by RT-PCR or antibody test.
• Symptoms related to Long Term COVID-19, defined as being investigated, diagnosed and followed by specialized infectious diseases physicians in the Long Term COVID-19 Outpatient Clinic, Central Region of Denmark, Aarhus University Hospital.
• Symptoms not attributable to other co-morbidity/condition.

Exclusion Criteria:

• Symptoms of acute COVID-19, as defined by The Danish Health Authorities.
• Women who are pregnant or breastfeeding, or with a positive pregnancy test as determined by a positive urine beta-human chorionic gonadotropin test during screening
• Hypersensitivity to the active ingredient or to any excipient of the medicinal product
• Known allergy to soy or peanuts.
• Individuals with reduced kidney or liver-function.
• Patients in anticoagulant therapy with vitamin K antagonists.
• Any condition that, in the Investigator's opinion, will prevent adequate compliance with study therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; A soft gelatin capsule containing soy oil, 5 capsules a day.
Active Comparator: Coenzyme Q10	Drug: Coenzyme Q10; Coenzyme Q10 (myoquinon) capsule 100mg, 5 capsules a day.; Other Names: Myoquinon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Coenzyme Q10 treatment in Long Term COVID-19 on number of self-reported symptoms of LTC measured by EQ-5D-5L questionnaire.	Number of self-reported symptoms measured by EQ-5D-5L questionnaire.	Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment
Effect of Coenzyme Q10 treatment in Long Term COVID-19 on number of self-reported symptoms of LTC measured by Long Term COVID-specific questionnaire.	Number of self-reported symptoms measured by Long Term COVID-specific questionnaire.	Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment
Effect of Coenzyme Q10 treatment in Long Term COVID-19 on severity (symptoms score) of self-reported symptoms of LTC measured by Long Term COVID-specific questionnaire.	Severity by symptom score of self-reported symptoms measured by Long Term COVID-specific questionnaire. The questionnaire consist of 32 questions with a graduation of 0-4, thus maximum number of points is 128 implying a high number of severe symptoms.	Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment
Effect of Coenzyme Q10 treatment in Long Term COVID-19 on severity (symptoms score) of self-reported symptoms of LTC measured by EQ-5D-5L questionnaire.	Severity by symptom score of self-reported symptoms measured by ED-5Q-5L questionnaire. The questionnaire consist of 5 questions with a graduation of 0-4, thus maximum number of points is 20 implying a high number of severe symptoms.	Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prolonged effect of Coenzyme Q10 treatment in Long Term COVID-19 on number of self-reported symptoms of LTC measured by Long Term COVID-specific questionnaire.	Number of self-reported symptoms measured by Long Term COVID-specific questionnaire.	Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment.
Prolonged effect of Coenzyme Q10 treatment in Long Term COVID-19 on number of self-reported symptoms of LTC measured by EQ-5D-5L questionnaire.	Number of self-reported symptoms measured by EQ-5D-5L questionnaire.	Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment.
Prolonged effect of Coenzyme Q10 treatment in Long Term COVID-19 on severity (symptoms score) of self-reported symptoms of LTC measured by Long Term COVID-specific questionnaire.	Severity by symptom score of self-reported symptoms measured by Long Term COVID-specific questionnaire. The questionnaire consist of 32 questions with a graduation of 0-4, thus maximum number of points is 128 implying a high number of severe symptoms.	Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment.
Prolonged effect of Coenzyme Q10 treatment in Long Term COVID-19 on severity (symptoms score) of self-reported symptoms of LTC measured by EQ-5D-5L questionnaire.	Severity by symptom score of self-reported symptoms measured by ED-5Q-5L questionnaire. The questionnaire consist of 5 questions with a graduation of 0-4, thus maximum number of points is 20 implying a high number of severe symptoms.	Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment.
Safety and tolerability of treatment with high-dose Coenzyme Q10 as measured by number of adverse events, adverse reactions, serious adverse events and serious adverse reactions.	Safety evaluation by incidence of adverse events, adverse reactions, serious adverse events and serious adverse reactions.	End of data collection after 20 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of auto-reactive antibodies in Long Term COVID-19	Investigation of auto-reactive antibodies at baseline compared to healthy controls (biobank samples), by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) against tissue proteins.	Blood samples week 6, 10, 16 and 20 after enrollment
Assessment of levels of Coenzyme Q10 plasma and PBMC in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo.	Assessment of baseline levels Coenzyme Q10 in plasma (nmol/L) and in PBMC (picogram / mg protein) , measured by High Performance Liquid Chromatography (HPLC), as this parameter previously has been associated with fatigue.	Blood samples after 6 weeks of treatment and after 6 weeks of placebo.
Quantitative proteomics in peripheral blood mononuclear cells (PBMCs) from Coenzyme Q10 treated patients versus placebo.	Relative quantification of the approximately four thousand most abundant proteins is performed by liquid chromatography (LC) tandem mass spectrometry (MS/MS). The quantitative signal is the MS peak intensities, with arbitrary scale. Statistically differentially regulated proteins are filtered out and described specifically.	Blood samples week 6, 10, 16 and 20 after enrollment
Assessment of cellular metabolic activity in PBMCs from Coenzyme Q10 treated patients by Seahorse analysis versus placebo.	Differential analysis of metabolic activities (Seahorse) in PBMCs from the treated patients versus placebo. Extracellular Acidification Rate (ECAR) (picomoles protons / minute) and Oxygen Consumption Rate (OCR) (picomoles O2 per minute) are measured to estimate glycolytic rate and respiration rates in the isolated PBMCs, respectively.	Blood samples week 6, 10, 16 and 20 after enrollment
Analysis of oxidative stress marker 8-isoprostane in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo.	Differential analysis of plasma samples from CoQ10 treated patients versus placebo, with respect to the oxidative stress marker 8-isoprostane by ELISA assay measured in picomoles 8-isoprostane per mL.	Blood samples week 6, 10, 16 and 20 after enrollment
Assessment of presence of cytokines in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo.	Differential analysis of plasma samples from CoQ10 treated patients versus placebo with Luminex to assess presence of cytokines measured as picomole cytokine / mL.	Blood samples week 6, 10, 16 and 20 after enrollment
Analysis of metabolites of the kynurenic pathway in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo.	Differential analysis of plasma samples from CoQ10 treated patients versus placebo with respect to metabolites of the kynurenic pathway by LC-MS/MS measured in nanomole per mL.	Blood samples week 6, 10, 16 and 20 after enrollment

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: University of Aarhus; Pharma Nord
• Investigators: Principal Investigator: Line Khalidan Vibholm, M.D., Ph.D, Department of Infections Diseases, Aarhus University Hospital

Publications and helpful links

General Publications

• Hansen KS, Mogensen TH, Agergaard J, Schiottz-Christensen B, Ostergaard L, Vibholm LK, Leth S. High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: A randomized, phase 2, crossover trial. Lancet Reg Health Eur. 2022 Nov 2:100539. doi: 10.1016/j.lanepe.2022.100539. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2021
• Primary Completion (Actual): February 10, 2022
• Study Completion (Actual): February 10, 2022

Study Registration Dates

• First Submitted: June 11, 2021
• First Submitted That Met QC Criteria: July 9, 2021
• First Posted (Actual): July 13, 2021

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Coenzyme Q10
• 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; Physiological Effects of Drugs; Micronutrients; Vitamins; Coenzyme Q10; Ubiquinone
• Other Study ID Numbers: QVID-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No