Examining the Effects of Mitochondrial Oxidative Stress in DCM

Study Overview
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Brief Summary
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Double blind, randomised, placebo-controlled trial of MitoQ (mitoquinol mesylate) in 106 patients with dilated cardiomyopathy, examining the effect of reducing mitochondrial oxidative stress on myocardial energetics and myocardial function using 31-phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance.

Official Title
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Examining the Effects of Mitochondrial Oxidative Stress in DCM

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: MitoQ Compound
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria idiopathic or familial DCM LVEF ≤45% on 2 imaging studies of any modality ≥3 months apart (may include CMR scan at baseline visit) on guideline therapy for ≥3 months as determined by usual clinicians sinus rhythm on 12-lead electrocardiogram plasma NT-pro-BNP >250ng/L for those >65 years and >100ng/L for those aged ≤65 years within the last 6 months (may include sample at baseline visit) Exclusion criteria current persistent atrial fibrillation contraindication to CMR estimated glomerular filtration rate (eGFR) <30mls/min current or planned pregnancy or current breast-feeding clear environmental trigger such as excess alcohol intake, cardiotoxic chemotherapy or peripartum presentation fibrosis burden >25% on CMR current cancer (other than non-melanoma skin cancers) current use of CoQ10 current participation in another randomised controlled trial

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MitoQ<br>Mitoquinol mesylate 40mg daily | Drug: MitoQ Compound<br>* Mitoquinol mesylate<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vanguard phase - change in myocardial PCr:ATP | The first 34 patients will enter a 3 months Vanguard phase. Change in myocardial PCr:ATP between baseline and follow-up will be measured using 31P magnetic resonance spectroscopy | 3 months | 
| Vanguard phase - change in circulating markers of oxidative stress | The first 34 patients will enter a 3 months Vanguard phase. Change in circulating oxLDL and F2isoprostanes will be measured in plasma samples | 3 months | 
| Primary outcome - change in LVESVi | Change in LVESVi (ml/m2) between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vanguard phase - change in skeletal muscle PCr recovery | The first 34 patients will enter a 3 months Vanguard phase. Change in skeletal muscle PCr recovery between baseline and follow-up will be measured using 31P magnetic resonance spectroscopy | 3 months | 
| Follow-on phase - change in LVEF | Change in LVEF (%) between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance | 12 months | 
| Follow-on phase - change in LVEDVi | Change in LVEDVi (ml/m2) between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance | 12 months | 
| Follow-on phase - change in GLS | Change in GLS between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance | 12 months | 
| Follow-on phase - change in NT-pro-BNP | Change in plasma concentrations of NT-pro-BNP (ng/L) between baseline and follow-up amongst all 106 patients | 12 months | 
| Follow-on phase - change in renal function | Change in creatinine and eGFR between baseline and follow-up amongst all 106 patients | 12 months | 
| Follow-on phase - change in symptom burden | Change in symptom score between baseline and follow-up amongst all 106 patients | 12 months | 
| Follow-on phase - change in exercise capacity | Change in 6 minute walk test distance between baseline and follow-up amongst all 106 patients | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Energetics, Mitochondria, Oxidative stress