High-dose coenzyme Q10 therapy versus placebo in patients with post COVID-19 condition: randomized, phase 2, crossover trial 2022 Hansen et al

[LarsSG]

Preprint and final publication threads merged
Final publication abstract further down the thread here

Abstract
Background: Post COVID-19 condition (PCC) is defined as symptoms lasting more than 12 weeks after developing COVID-19. Evidence of mitochondrial dysfunction has been reported in peripheral blood mononuclear cells obtained from patients with COVID-19. We hypothesized that PCC is caused by prolonged mitochondrial dysfunction. Given that coenzyme Q10 (CoQ10) can improve mitochondrial function, we examined whether high-dose CoQ10 can reduce the number and/or severity of PCC-related symptoms.

Methods: In this placebo-controlled, double-blind, 2x2 crossover interventional trial, participants were recruited from two centres at Aarhus University Hospital and Gødstrup Hospital, Denmark. They were randomly assigned to receive either oral capsules of CoQ10 in a dose of 500 mg/day or placebo for six weeks, with crossover treatment after a four-week washout period. The ED-5Q and a PCC-symptom specific questionnaire were completed by the participants at 5 visits during the 20-week study period. The primary endpoint was the change in the number and/or severity of PCC-related symptoms after the six-week intervention compared to placebo. Participants who completed the two-dosing period were included in the primary analysis, while all participants receiving one dose were included in safety assessment.

Findings: From May 25th, 2021, to September 22nd, 2021, 121 participants underwent randomization, and 119 completed both dosing periods – 59 and 60 in group A and B, respectively. At baseline, the mean PCC-related symptom score was 43·06 (95% CI: 40·18;45·94), and the mean EQ-5D health index was 0·66 (95% CI: 0·64;0·68). The difference between CoQ10 and placebo was not significant with respect to either the change in EQ-5D health index (with a mean difference of 0·01; 95% CI: -0·02;0·04; p =0·45) or the change in PCC-related symptom score (with a mean difference of -1·18; 95% CI: -3·54;1·17; p =0·32).

Interpretation: We conclude that CoQ10 treatment does not appear to significantly reduce the number or severity of PCC-related symptoms when compared to placebo.

Preprint

 

[Hutan]

The result is hardly a surprise given what we know about CoQ10 for ME/CFS. The surprise is a well-structured trial with a placebo and double-blinding, and researchers willing to report a negative result.

Danish team - Aarhus University

 

[Peter T]

The result is hardly a surprise given what we know about CoQ10 for ME/CFS. The surprise is a well-structured trial with a placebo and double-blinding, and researchers willing to report a negative result.

Danish team - Aarhus University

What has gone wrong, this is not how ‘evidence based medicine’ is now conducted?

 

[Hutan]

This team made a "PCC-symptom specific questionnaire" with each symptom assessed using a 0 to 4 scale. The list looks pretty good, although it is missing PEM and orthostatic intolerance - maybe someone could talk to them about ME/CFS criteria? The paper has a lot of good figures that clearly explain what was done in this study. I really like this side-by-side heat map of symptom change over the course of the study. There's a lot of information there, including what Long Covid looks like:



It's very nice to feel positive about the quality of a study, to feel, 'ok, here is a solid bit of knowledge', even if it is just about what does not work. I hope this team will do more studies like this - I think they could cut a great swathe through many of the suggested treatments for Long Covid and ME/CFS. And hopefully they will find something that does actually work.

Here are the authors of the paper
Aarhus University - Department of Infectious Diseases

Kristoffer Skaalum Hansen
Trine Hyrup Mogensen
Jane Agergaard
Berit Schiøttz-Christensen
Lars Jørgen Østergaard
Line Khalidan Vibholm
Steffen Leth


Kristoffer Hansen's profile on Researchgate suggests that we will hear more from him

Experimental treatment research on Long Term COVID-19.
Metabolic and immunological investigations on the pathogenesis of Long Term COVID-19

 

[borko2100]

The result is hardly a surprise given what we know about CoQ10 for ME/CFS. The surprise is a well-structured trial with a placebo and double-blinding, and researchers willing to report a negative result.

Yes the researchers need to be commended for doing this study. They could have easily skipped the control group and gotten a positive result (due to placebo). Instead they choose to make a robust and properly designed study, unlike many others who do these kind of uncontrolled studies either to pad their resume or to push some sort of proprietary supplement.

 

[Tia]

Yes the researchers need to be commended for doing this study. They could have easily skipped the control group and gotten a positive result (due to placebo). Instead they choose to make a robust and properly designed study, unlike many others who do these kind of uncontrolled studies either to pad their resume or to push some sort of proprietary supplement.

Yes, the value of ruling things out shouldn't be underestimated. Just on a personal level, if there had been proper trials into all the things I've tried over the years it could have saved me ££££ as well as much confusion and disappointment. (And £ and good mental health are two things that are very useful when you have ME!)

 

[Sly Saint]

Summary
Background
Post COVID-19 condition (PCC) is defined as symptoms lasting more than 12 weeks after developing COVID-19. Evidence of mitochondrial dysfunction has been reported in peripheral blood mononuclear cells obtained from patients with COVID-19. We hypothesized that PCC is caused by prolonged mitochondrial dysfunction. Given that coenzyme Q10 (CoQ10) can improve mitochondrial function, we examined whether high-dose CoQ10 can reduce the number and/or severity of PCC-related symptoms.
Methods
In this placebo-controlled, double-blind, 2 × 2 crossover interventional trial, participants were recruited from two centres at Aarhus University Hospital and Gødstrup Hospital, Denmark. They were randomly assigned to receive either oral capsules of CoQ10 in a dose of 500 mg/day or placebo for 6 weeks, with crossover treatment after a 4-week washout period. The ED-5Q and a PCC-symptom specific questionnaire were completed by the participants at 5 visits during the 20-week study period. The primary endpoint was the change in the number and/or severity of PCC-related symptoms after the 6-week intervention compared to placebo. Participants who completed the two-dosing period were included in the primary analysis, while all participants receiving one dose were included in safety assessment.
Findings
From May 25th, 2021, to September 22nd, 2021, 121 participants underwent randomization, and 119 completed both dosing periods – 59 and 60 in group A and B, respectively. At baseline, the mean PCC-related symptom score was 43.06 (95% CI: 40.18; 45.94), and the mean EQ-5D health index was 0.66 (95% CI: 0.64; 0.68). The difference between CoQ10 and placebo was not significant with respect to either the change in EQ-5D health index (with a mean difference of 0.01; 95% CI: −0.02; 0.04; p = 0.45) or the change in PCC-related symptom score (with a mean difference of −1.18; 95% CI: −3.54; 1.17; p = 0.32).
Interpretation
Based on self-reported data, CoQ10 treatment does not appear to significantly reduce the number or severity of PCC-related symptoms when compared to placebo. However, we observed a significant spontaneous improvement on both scores regardless of treatment during 20 weeks observation.

https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(22)00235-6/fulltext

 

[BrightCandle]

This precisely the short focused trials on recommended supplements we need. Also using a control is critical because of that last point, seeing an improvement on both sides of the trial throughout. I expected a lot of the long hauler trials on supplements will end up this way and a bunch of the drugs too since almost all of them are ME/CFS recommendations and they didn't work.

 

[John Mac]

This precisely the short focused trials on recommended supplements we need. Also using a control is critical because of that last point, seeing an improvement on both sides of the trial throughout. I expected a lot of the long hauler trials on supplements will end up this way and a bunch of the drugs too since almost all of them are ME/CFS recommendations and they didn't work.

And this is exactly why all claims of success in trials of CBT are such nonsense as there is no control group.

 

[Creekside]

Yay! A published study that doesn't claim to be an effective treatment. There should be awards/rewards for publishing negative findings. Maybe national/international awards for most useful negative findings?

 

[Hutan]

Threads on the preprint and final publication have been merged

 

[RedFox]

Kudos to the authors. They interpreted their answers honestly instead of trying to puff them up. It's not a positive answer...but I will welcome any solid answer in this disease, because even "no's" get us closer to the truth.

 

[RedFox]

We seem to have missed the fact that this paper is a milestone: It's the first completed, rigorous trial of a long Covid treatment I know of.