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

• ClinicalTrials.gov Identifier: NCT04960215
• Recruitment Status: Completed
• First Posted: July 13, 2021
• Last Update Posted: May 6, 2022
• Sponsor: Aarhus University Hospital
• Collaborators: University of Aarhus; Pharma Nord
• Information provided by (Responsible Party): University of Aarhus ( Aarhus University Hospital )

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Covid19; Long Term Covid19	Drug: Coenzyme Q10; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Coenzyme Q10 as Treatment for Long Term COVID-19
• Actual Study Start Date: May 25, 2021
• Actual Primary Completion Date: February 10, 2022
• Actual Study Completion Date: February 10, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Effect of Coenzyme Q10 treatment in Long Term COVID-19 on number of self-reported symptoms of LTC measured by EQ-5D-5L questionnaire. [ Time Frame: Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment ]
   Number of self-reported symptoms measured by EQ-5D-5L questionnaire.
2. 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. [ Time Frame: Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment ]
   Number of self-reported symptoms measured by Long Term COVID-specific questionnaire.
3. 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. [ Time Frame: Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment ]
   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.
4. 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. [ Time Frame: Changes from baseline questionnaire response to questionnaire response after 6 weeks of treatment ]
   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.

Secondary Outcome Measures :

1. 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. [ Time Frame: Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment. ]
   Number of self-reported symptoms measured by Long Term COVID-specific questionnaire.
2. 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. [ Time Frame: Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment. ]
   Number of self-reported symptoms measured by EQ-5D-5L questionnaire.
3. 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. [ Time Frame: Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment. ]
   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.
4. 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. [ Time Frame: Changes from baseline questionnaire response to questionnaire response 4 weeks after ended treatment. ]
   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.
5. 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. [ Time Frame: End of data collection after 20 weeks. ]
   Safety evaluation by incidence of adverse events, adverse reactions, serious adverse events and serious adverse reactions.

Other Outcome Measures:

1. Presence of auto-reactive antibodies in Long Term COVID-19 [ Time Frame: Blood samples week 6, 10, 16 and 20 after enrollment ]
   Investigation of auto-reactive antibodies at baseline compared to healthy controls (biobank samples), by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) against tissue proteins.
2. Assessment of levels of Coenzyme Q10 plasma and PBMC in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo. [ Time Frame: Blood samples after 6 weeks of treatment and after 6 weeks of 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.
3. Quantitative proteomics in peripheral blood mononuclear cells (PBMCs) from Coenzyme Q10 treated patients versus placebo. [ Time Frame: Blood samples week 6, 10, 16 and 20 after enrollment ]
   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.
4. Assessment of cellular metabolic activity in PBMCs from Coenzyme Q10 treated patients by Seahorse analysis versus placebo. [ Time Frame: Blood samples week 6, 10, 16 and 20 after enrollment ]
   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.
5. Analysis of oxidative stress marker 8-isoprostane in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo. [ Time Frame: Blood samples week 6, 10, 16 and 20 after enrollment ]
   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.
6. Assessment of presence of cytokines in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo. [ Time Frame: Blood samples week 6, 10, 16 and 20 after enrollment ]
   Differential analysis of plasma samples from CoQ10 treated patients versus placebo with Luminex to assess presence of cytokines measured as picomole cytokine / mL.
7. Analysis of metabolites of the kynurenic pathway in Long Term COVID-19 patients treated with Coenzyme Q10 versus placebo. [ Time Frame: Blood samples week 6, 10, 16 and 20 after enrollment ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Denmark

Department of Infectious Diseases

Aarhus, Aarhus N, Denmark, 8200

Sponsors and Collaborators

Aarhus University Hospital

University of Aarhus

Pharma Nord

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. 2023 Jan;24:100539. doi: 10.1016/j.lanepe.2022.100539. Epub 2022 Nov 2.

• Responsible Party: Aarhus University Hospital
• ClinicalTrials.gov Identifier: NCT04960215
• Other Study ID Numbers: QVID-001
• First Posted: July 13, 2021
• Last Update Posted: May 6, 2022
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Aarhus ( Aarhus University Hospital ):

Coenzyme Q10

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Ubiquinone; Coenzyme Q10; Micronutrients; Physiological Effects of Drugs; Vitamins