Table 1.
Current randomized trials of pharmacological agents targeting mitochondrial dysfunction
| Drug | Disease | Mode of action | Dose | Enrolment & age | Result | Status | Period | Identifier |
|---|---|---|---|---|---|---|---|---|
| CoQ10 | PMDa) | Antioxidant | 10 mg/kg/d (400 mg/d) | 24 (12 m– 17 y) | No significant difference in McMaster gross motor function and pediatric quality of life scale | Phase III/Completed | 6 months | NCT00432744 |
| CKDb) | Antioxidant | 1000 mg/d | 26 (30 y–79 y) | Increased free fatty acids and decreased complex medium- and long-chain triglycerides. No significant improvement in VO2 peak or total work efficiency | Phase II/Completed | 6 weeks | NCT03579693 | |
| ALSc) | Antioxidant | 1800-2700 mg/d | 185 (21 y–85 y) | No significant difference in the ALS Functional Rating Scale-revised (ALSFRSr) Score | Phase II/Completed | 9 months | NCT00243932 | |
| Ubiquinol MitoQ (MTA)e) | PDd) | Antioxidant | 600 mg/d | 11 (40 y–75 y) | No results reported | Phase II/Completed | 24 weeks | NCT03061513 |
| CVDf) | Antioxidant | 20 mg/d | 60 (45 y–75 y) | - | NA/Recruiting | 8 weeks | NCT05561556 | |
| CVD | Antioxidant | 20 mg/d | 112 (>60 y) | - | Phase II/Recruiting | 3 months | NCT04851288 | |
| COPD | Antioxidant | NA | 24 (>40 y) | - | NA/Recruiting | 6 weeks | NCT05605548 | |
| Dilated cardiomyopathy | Antioxidant | 40 mg/d | 106 (>16 y) | - | Phase II/Recruiting | 3 months | NCT05410873 | |
| Heart failure | Antioxidant | 40 mg/d | 60 (50 y–75 y) | - | NA/Not recruiting | 28 days | NCT03586414 | |
| Multiple Sclerosis | Antioxidant | 20–40 mg/d | 60 (18 y– 70 y) | - | Phase I & II/Recruiting | 12 weeks | NCT04267926 | |
| SS-31 (MTA) | Friedreich Ataxia | Antioxidant | 20–30, 40–60 mg/d | 18 (>16 y) | - | Active, not recruiting | 52 weeks | NCT05168774 |
| SKQ1 (MTA) | Dry Eye Syndrome | Antioxidant | 0.155–1.55 µg/mL | 90 ( > 18 y) | Significant improvements in corneal fluorescein staining and lissamine green staining in the central region and lid margin redness, also in the dry eye symptoms | Phase II/Completed | 28 days | NCT02121301 |
| Dry Eye Syndrome | Antioxidant | 1.55 µg/mL | 452 (>18 y) | Significant impact on clearing of Central Corneal Fluorescein Staining (CCFS) and improvement of Best Corrected Visual Acuity (BCVA) at day 28 | Phase III (VISTA-1)/Completed | 28 days | NCT03764735 | |
| Dry Eye Syndrome | Antioxidant | 1.55 µg/mL | 610 (>18 y) | Significant impact on clearing of Central Corneal Fluorescein Staining (CCFS) and improvement of Best Corrected Visual Acuity (BCVA) at day 28 | Phase III (VISTA-2)/Completed | 28 days | NCT04206020 | |
| KH176 | PMD | Antioxidant | 200 mg/d | 20 (>18 y) | No results available | Phase II/Completed | 28 days | NCT02909400 |
| PMD | Antioxidant | NA | 24 (0 month - 17 y) | - | Phase II/Recruiting | 26 weeks | NCT04846036 | |
| PMD | Antioxidant | 100–200 mg/d | 27 (>18 y) | No results available | Phase II/Completed | 28 days | NCT04165239 | |
| PMD | Antioxidant | 800–2000 mg | 32 (18 y–55 y) | Well tolerated up to single doses of 800 mg and multiple doses of 400 mg b.i.d. and has a pharmacokinetic profile supportive for a twice daily dosing. | Phase I/Completed | 7 days | NCT02544217 | |
| Acipimox | Sarcopenia | NAD+ boosting | 750 mg/d | 16 (65 y–75 y) | No results available | NA/Completed | 14 days | NCT02792621 |
| Type 2 Diabetes | NAD+ boosting | 750 mg/d | 31 (40 y–70 y) | Improved insulin sensitivity of type 2 diabetes patients by ∼27% and reduced H2O2 production by ∼45%, but did not improve basal or insulin-stimulated mitochondrial oxidative capacity | NA/Completed | 14 days | NCT00943059 | |
| Obesity | NAD+ boosting | 750 mg/d | 39 (18 y–55 y) | Reduced free fatty acids, improved fasting measures of glucose homeostasis, lipids, and adiponectin. No effect on mitochondrial function, mitochondrial density, or muscle insulin sensitivity | Phase II/Completed | 6 months | NCT01488409 | |
| Type 1 Diabetes | NAD+ boosting | 1000 mg/d | 28 (25 y–59 y) | No results available | Phase III/Completed | 16 weeks | NCT01816165 | |
| NRg) | CKD | NAD+ boosting | 1200 mg/d | 26 (30 y–79 y) | Significantly altered TCA cycle intermediates and glutamate and decreased a broad range of lipid groups including triglycerides and ceramides. No significant improvement in VO2 peak or total work efficiency | Phase II/Completed | 6 weeks | NCT03579693 |
| Metformin | Type 1 Diabetes | Unknown | 500–2000 mg/d | 23 (20 y–59 y) | Results not available | Phase IV/Completed | 6 weeks | NCT01813929 |
| PMD | Complex I inhibitor | 500 mg | 61 (>18 y) | Results not available | Phase II/Completed | 2 hours | NCT02500628 | |
| Idebenone | MELAS Syndrome | Antioxidant, ETC substrate | 900–2250 mg/day | 27 (8 y–65 y) | Results not available | Phase II/Completed | 1 month | NCT00887562 |
| PPMSh) | ETC substrate | 10–50 mg/kg/d (2250 mg/d) | 85 (18–65 y) | No significant improvement in CSF GDF15 levels | Phase I & II/Completed | 3 years | NCT00950248 | |
| Friedreich’s Ataxia | Antioxidant, ETC substrate | 900–2250 mg/day | 70 (8 y–17 y) | No significant change in the International Cooperative Ataxia Rating Scale (ICARS) | Phase III/Completed | 6 months | NCT00537680 | |
| Rosiglitazone | HIV Infections | PPAR agonist | 8 mg/d | 71 (>18 y) | Results not available | Phase II/Completed | 48 weeks | NCT00367744 |
| MIN-102 | Friedreich Ataxia | PPAR agonist | 15 mg/ml | 39 (12 y–60 y) | No results available | Phase II/Completed | 48 weeks | NCT03917225 |
| REN001 | Mitochondrial myopathy | PPAR agonist | NA | 213 (>18 y) | - | Phase II/Completed | 24 weeks | NCT04535609 |
| Resveratrol | Mitochondrial myopathy | STACs | 1000 mg/d | 20 (18 y–80 y) | No results available | NA/Completed | 20 weeks | NCT03728777 |
| Aging | STACs | 1000–1500 mg/d | 59 (>65 y) | Results not available | Phase II/Completed | 3 months | NCT02123121 | |
| Type 1 Diabetes | STACs | 1000 mg/d | 24 (>18 y) | - | Phase I/Recruiting | 12 weeks | NCT04449198 | |
| Friedreich Ataxia | STACs | 2000 mg/d | 25 (>16 y) | - | Active, not recruiting | 24 weeks | NCT03933163 | |
| Urolithin A | Aging | Fission induction | 1000 mg/d | 50 (45 y–70 y) | - | NA/Recruiting | 28 days | NCT05735886 |
| HU6 | Type 2 Diabetes Obesity | Mitochondrial uncoupler | 450–600 mg/d | 48 (18 y–70 y) | - | Phase II/Not yet recruiting | 6 months | NCT06104358 |
a)PMD primary mitochondrial disease
b)CKD chronic kidney disease
c)ALS amyotrophic lateral sclerosis
d)PD Parkinson’s disease
e)MTA mitochondria-targeted agent
f)CVD cardiovascular disease
g)NR nicotinamide riboside
h)PPMS primary progressive multiple sclerosis