Dilated Cardiomyopathy
Conditions
Keywords
Energetics, Mitochondria, Oxidative stress
Brief summary
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.
Interventions
DRUGMitoQ Compound
Mitoquinol mesylate
DRUGPlacebo
Placebo
Sponsors
British Heart Foundation
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. idiopathic or familial DCM 2. LVEF ≤45% on 2 imaging studies of any modality ≥3 months apart (may include CMR scan at baseline visit) 3. on guideline therapy for ≥3 months as determined by usual clinicians 4. sinus rhythm on 12-lead electrocardiogram 5. 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
1. current persistent atrial fibrillation 2. contraindication to CMR 3. estimated glomerular filtration rate (eGFR) \<30mls/min 4. current or planned pregnancy or current breast-feeding 5. clear environmental trigger such as excess alcohol intake, cardiotoxic chemotherapy or peripartum presentation 6. fibrosis burden \>25% on CMR 7. current cancer (other than non-melanoma skin cancers) 8. current use of CoQ10 9. current participation in another randomised controlled trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vanguard phase - change in myocardial PCr:ATP | 3 months | 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 |
| Vanguard phase - change in circulating markers of oxidative stress | 3 months | The first 34 patients will enter a 3 months Vanguard phase. Change in circulating oxLDL and F2isoprostanes will be measured in plasma samples |
| Primary outcome - change in LVESVi | 12 months | Change in LVESVi (ml/m2) between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Follow-on phase - change in GLS | 12 months | Change in GLS between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance |
| Follow-on phase - change in NT-pro-BNP | 12 months | Change in plasma concentrations of NT-pro-BNP (ng/L) between baseline and follow-up amongst all 106 patients |
| Follow-on phase - change in LVEF | 12 months | Change in LVEF (%) between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance |
| Follow-on phase - change in symptom burden | 12 months | Change in symptom score between baseline and follow-up amongst all 106 patients |
| Follow-on phase - change in exercise capacity | 12 months | Change in 6 minute walk test distance between baseline and follow-up amongst all 106 patients |
| Follow-on phase - change in renal function | 12 months | Change in creatinine and eGFR between baseline and follow-up amongst all 106 patients |
| Vanguard phase - change in skeletal muscle PCr recovery | 3 months | 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 |
| Follow-on phase - change in LVEDVi | 12 months | Change in LVEDVi (ml/m2) between baseline and follow-up amongst all 106 patients measured using cardiovascular magnetic resonance |
Countries
United Kingdom
Outcome results
None listed