CoQ10 Effects on MDM Liver Fat Via FibroTouchI.

Official title

The Effect of Coenzyme Q10 on Quantitative Changes in Hepatic Fat in Patients With Mitochondrial Diabetes

Overview

Mitochondrial diabetes mellitus (MDM) is a rare subtype of diabetes caused by mitochondrial dysfunction, often accompanied by hepatic steatosis. Coenzyme Q10 (CoQ10), a key electron carrier and antioxidant, may improve mitochondrial function and lipid metabolism. This prospective study aims to evaluate the effect of 12-week CoQ10 supplementation (300 mg/day) on liver fat content (assessed by FibroTouch CAP ) in MDM patients with m.3243A\>G mutation. An exploratory case-control design will compare baseline characteristics among MDM patients, type 1 diabetes patients, and healthy controls. This study is the first to explore the link between mitochondrial defects and hepatic fat accumulation specifically in MDM, and to test CoQ10 as a potential therapy, offering new insights for both MDM and MAFLD management.

Detailed description

1. Research Materials Coenzyme Q10: Utilize Coenzyme Q10 formulations that comply with Good Manufacturing Practice (GMP) standards (e.g., Bio-Quinone or equivalent quality products), with each capsule containing 100 mg of Coenzyme Q10 and excipients such as soybean oil and beeswax.

Control Medication: None. 2. Treatment Protocols Mitochondrial Diabetes Group: On the basis of maintaining the original hypoglycemic treatment regimen (primarily insulin, avoiding metformin), add Coenzyme Q10 at a dose of 100 mg three times daily (total dose of 300 mg/day) for 12 consecutive weeks.

Type 1 Diabetes Control Group and Healthy Control Group: Only undergo baseline assessments without intervention.

Concomitant Medication Regulations:

Maintain the patient's original hypoglycemic treatment regimen unchanged. Avoid using medications that may affect mitochondrial function (e.g., minimize or switch metformin and statins if possible).

Do not add other medications or supplements with antioxidant or mitochondrial protective effects during the study period.

If adjustments to hypoglycemic medications are necessary due to clinical conditions, record the medication name, dosage, and reasons for adjustment in detail.

Interventions

• Drug Coenzyme Q10 (drug)
  This prospective study aims to evaluate the effect of 12 week CoQ10 supplementation (300 mg/day) on liver fat content (assessed by FibroTouch CAP) in MDM patients with m.3243A\>G mutation. An exploratory case control design will compare baseline characteristics among MDM patients, type 1 diabetes patients, and healthy controls.
• Other Only undergo baseline assessments without intervention.
  Only undergo baseline assessments without intervention.
• Other Only undergo baseline assessments without intervention.
  Only undergo baseline assessments without intervention.

Primary outcome measures

• Liver Fat Quantification [Time frame: From enrollment to the end of treatment at 12 weeks]

Secondary outcome measures (1)

• Blood biochemistry indicators [Time frame: From enrollment to the end of treatment at 12 weeks]

Eligibility criteria

1\. Mitochondrial Diabetes Group

Inclusion criteria

• Confirmed as a carrier of the mitochondrial DNA m.3243A>G mutation through genetic testing;
• Meeting the diagnostic criteria for diabetes (WHO 1999 diagnostic criteria);
• Aged between 18 and 70 years;
• Willing to participate and having signed the informed consent form.

Exclusion criteria

• Type 1 or type 2 diabetes (not caused by mitochondrial gene mutations);
• Comorbid with viral hepatitis, drug-induced hepatitis, alcoholic liver disease, Wilson's disease, or other specific diseases that can lead to fatty liver;
• Severe cardiac, pulmonary, or renal insufficiency;
• Pregnant or lactating women;
• Having used coenzyme Q10 or other mitochondrial-targeted drugs within the past 3 months;
• Having contraindications to MRI examination;
• Having experienced infection, surgery, or major trauma within the past 4 weeks.

Withdrawal/Dropout Criteria:

• The subject withdraws informed consent;
• The occurrence of serious adverse events;
• Loss to follow-up;
• Medication adherence that continued participation in < 80%;
• The researcher believes the study is not in the best interest of the subject. 2. Type 1 Diabetes Control Group

Inclusion criteria

• Meeting the diagnostic criteria for type 1 diabetes, with positive islet autoantibodies (GAD, IA-2, ICA, etc.);
• Aged between 18 and 70 years;
• Willing to participate and having signed the informed consent form.

Exclusion criteria

Same as the exclusion criteria (1) to (7) for the mitochondrial diabetes group. 3. Healthy Adult Control Group

Inclusion criteria

• No history of diabetes, with fasting blood glucose < 5.6 mmol/L and HbA1c < 5.7%;
• Aged between 18 and 70 years;
• Willing to participate and having signed the informed consent form.

Exclusion criteria

Same as the exclusion criteria (1) to (7) for the mitochondrial diabetes group.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• The 95th hospital of Putian — Putian

Publications

• Ferreira F, Goncalves Bacelar C, Lisboa-Goncalves P, Paulo N, Quental R, Nunes AT, Silva R, Tavares I. Renal manifestations in adults with mitochondrial disease from the mtDNA m.3243A>G pathogenic variant. Nefrologia (Engl Ed). 2023 Dec;43 Suppl 2:1-7. doi: 10.1016/j.nefroe.2024.01.017. PMID 38355238
• Ardekani A, Tabrizi R, Maleki E, Bagheri Lankarani K, Heydari ST, Moradinazar M, Akbari M. Effects of coenzyme Q10 supplementation on lipid profiles and liver enzymes of nonalcoholic fatty liver disease (NAFLD) patients: A systematic review and meta-analysis of randomized controlled trials. Food Sci Nutr. 2023 Mar 13;11(6):2580-2588. doi: 10.1002/fsn3.3315. eCollection 2023 Jun. PMID 37324909
• Fromenty B, Roden M. Mitochondrial alterations in fatty liver diseases. J Hepatol. 2023 Feb;78(2):415-429. doi: 10.1016/j.jhep.2022.09.020. Epub 2022 Oct 7. PMID 36209983
• Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 2021 May 13;184(10):2537-2564. doi: 10.1016/j.cell.2021.04.015. PMID 33989548
• Chen Y, Du X, Kuppa A, Feitosa MF, Bielak LF, O'Connell JR, Musani SK, Guo X, Kahali B, Chen VL, Smith AV, Ryan KA, Eirksdottir G, Allison MA, Bowden DW, Budoff MJ, Carr JJ, Chen YI, Taylor KD, Oliveri A, Correa A, Crudup BF, Kardia SLR, Mosley TH Jr, Norris JM, Terry JG, Rotter JI, Wagenknecht LE, Halligan BD, Young KA, Hokanson JE, Washko GR, Gudnason V, Province MA, Peyser PA, Palmer ND, Spelio PMID 37709864

Identifiers

NCT: NCT07748130 · 2025-js020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗