Effect of CoQ10 on the Outcome of MAFLD Patients

Sponsor

Ain Shams University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05984745

Collaborator

(none)

166

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

So far there has been no universal treatment for MAFLD since it has a complex etiology that involves ethnic, genetic, metabolic and environmental factors. However, therapeutic life changes including: diet, weight loss, and physical activity remain the cornerstone of treatment and is recommended by both American and European associations.

Inflammatory biomarkers, such as tumor necrosis factor-alpha, and adipokines play key roles in the pathogenesis of MAFLD, hence, the anti-inflammatory and antioxidant effects of coenzyme Q10 especially at high doses that have not been tested are hypothesized to have a beneficial role in improving the systemic inflammation and biochemical variables.

This study is conducted to test this hypothesis

Condition or Disease	Intervention/Treatment	Phase
Fatty Liver NAFLD	Drug: Coenzyme Q10 Forte® capsules	Phase 2

Detailed Description

The liver disease with the most continuously rising prevalence rates is metabolic-dysfunction associated fatty liver disease (MAFLD), making us arrive at a conclusion that it might be the liver disease epidemic of the 21st century. It is increasingly diagnosed in many developed and developing countries and is considered the most common cause of chronic liver disease among patients with type 2 diabetes mellitus (T2DM). By 2030, it will be the leading cause for hepatocellular carcinoma (HCC) related liver transplantation (LTx) in western countries.

A number of studies have suggested that metabolic associated co-morbidities, such as obesity, type 2 DM, CVD, dyslipidemia, hypertension, metabolic syndrome, hypothyroidism, OSAS, PCOS are major risk factors for MAFLD.

It encompasses a wide spectrum of histological pattern, ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis.

The global prevalence of MAFLD is currently estimated to be 25%, but the highest rates are reported from the Middle East 31.8% and South America 30.5%, followed by Asia 27.4%, the USA 24% and Europe 23.7%, whereas MAFLD is less common in Africa 13.5%.

Coenzyme Q10 (CoQ10) or ubiquinone is a lipid-soluble and vitamin-like compound, which acts as a pivotal cofactor in the mitochondrial respiratory chain in addition to its role as a natural scavenger of free radicals. It is synthesized by cells of the body and also found in abundance in the human diet. Recent evidence suggests that CoQ10 supplementation might be useful in improving and preventing pathological conditions such as metabolic syndrome, hypertension, diabetes, liver diseases, and insulin resistance Because of its antioxidant activity, it seems that CoQ10 can prevent activation of the inflammatory signaling pathway. Many studies have shown that administration of CoQ10 reduced hepatic oxidative stress and inflammation. Also, other studies observed that CoQ10 supplementation reduced TNF-α production and serum levels of liver aminotransferase and decreased NF-kB expression. In addition, a previously published study showed that a dose of 100 mg/day of CoQ10 for 4 weeks can improve serum AST levels, total antioxidant capacity and waist circumference, but it had a non-significant effect on insulin resistance and MDA levels. The same result was found in the study by Esfahani et al. reporting improvement in AST and ALT concentrations and lower grades of portal inflammation and hepatocellular liver necrosis in thioacetamide-induced liver damage in rats. Yet, some contradicting results were reported by Hodgson et al. were they found a non-significant reduction in body weight after CoQ10 supplementation in patients with T2DM. These contradictions were addressed by Faresi et al. where they tested the effect of the same oral dose of CoQ10 used by Farhangi et al. for 12 weeks, where it had beneficial effects on serum levels of TNF-a, hs-CRP, hepatic enzymes, adiponectin, and NAFLD grades as well as near-significant changes in serum leptin among patients with NAFLD. However, serum IL-6 levels and AAR remained unchanged after CoQ10 supplementation.

Till this day, only a few small studies tried to investigate the effect of CoQ10 administration on the degree of steatosis in MAFLD patients and their results failed to show a clear effect, due to the conflicting and limited data. Hence, this encouraged us to study the efficacy and tolerability of a higher dose of CoQ10 especially that it can be safely administered up to a dose of 1200 mg/day. In addition, CoQ10 showed promising effects in previous studies, so the general recommendation was to study its effect in a larger study population, for longer periods.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

166 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Coenzyme Q10 on the Outcome of Metabolic Dysfunction-Associated Fatty Liver Disease Patients

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control group Patients will receive the standard conventional care which is mainly therapeutic life changes
Experimental: Test Group Patients will receive Coenzyme Q10 Forte® (MEPACO Pharmaceutical Company, Cairo, Egypt) capsules in a dose of 100 mg twice per day 1 capsule every 12 hours for twelve weeks, in addition to the standard conventional care.	Drug: Coenzyme Q10 Forte® capsules Coenzyme Q10 in the form of soft gelatin capsules, each capsule containing 100 mg

Arm

Intervention/Treatment

No Intervention: Control group

Patients will receive the standard conventional care which is mainly therapeutic life changes

Experimental: Test Group

Patients will receive Coenzyme Q10 Forte® (MEPACO Pharmaceutical Company, Cairo, Egypt) capsules in a dose of 100 mg twice per day 1 capsule every 12 hours for twelve weeks, in addition to the standard conventional care.

Drug: Coenzyme Q10 Forte® capsules

Coenzyme Q10 in the form of soft gelatin capsules, each capsule containing 100 mg

Outcome Measures

Primary Outcome Measures

Change in liver steatosis degree [Baseline and at 12 weeks]
Improvement in steatosis degree will be assessed using Fibro-CAP scoring measured in decibels per meter (dB/m) and ranges from 100-400, where 238 to 260 dB/m represents 11-33% fatty change in the liver, 260 to 290 dB/m represents 34-66% fatty change in the liver and > 290 dB/m represents almost 67% or more fatty change in the liver.

Secondary Outcome Measures

Change in serum levels of liver transaminases (AST and ALT) 3 months post treatment with Coenzyme Q10 [Baseline and at 12 weeks]
Levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) will be measured in serum where normal serum ALT is 7-56 U/L and normal serum AST is 0 to 35 U/L.
Change in serum levels of tumor necrosis factor-alpha (TNF-α) 3 months post treatment with Coenzyme Q10 [Baseline and at 12 weeks]
TNF-α levels will be assessed in serum
Change in the quality of life of MAFLD patients [Baseline and at 12 weeks]
Quality of life will be assessed using the Chronic Liver Disease (CLD) questionnaire
Study the drug's effect on kidney functions by measuring serum creatinine levels [Baseline and at 12 weeks]
Serum creatinine levels will be measured where the normal range is 0.74 to 1.35 mg/dL (61.9 to 114.9 µmol/L) for men and 0.59 to 1.04 mg/dL (53 to 97.2 µmol/L) for women

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

All study subjects and prior to consenting to the ICF, laboratory and imaging work-up will be evaluated for the presence of three out of five criteria for metabolic dysregulation in the context of metabolic -dysfunction associated fatty liver disease (MAFLD):

Waist circumference (WC) ≥ 102/88 cm for men and women respectively.
HDL cholesterol <40 mg/dl in men and <50 mg/dl in women or on specific drug therapy.
Plasma Triglycerides ≥ 150 mg/dl or on specific drug therapy.
Blood pressure ≥130 and/or ≥ 85 or on specific anti-hypertensive therapy.
Fasting blood glucose ≥ 100 mg/dl or on specific anti hyperglycemic therapy

Patients who agree to sign an informed consent
Adult patients >18 years old.
Males and females
Willing to comply with procedures and follow up
Elevated serum transaminases (1-4 times the ULN)
Imaging evidence of fatty liver:

pelviabdominal ultrasound and Fibro- CAP study

Exclusion Criteria:

Pregnancy or lactating
Physical or mental abnormalities
HCV infection
HBV infection
Anaemia
Thrombocytopenia
Haematological malignancies
Ongoing alcoholism (Male: >30g/day, Female: >20g/day)
Patients with renal failure
Autoimmune hepatitis
Celiac disease
Wilson's disease
Hemochromatosis
Drugs: Tamoxifen, Valproic acid, Amiodarone, Methotrexate, Steroids, Anticoagulants, All anti-oxidative stress agents, Cos, IUD
Chronic use of systematically immunosuppressive agent or drugs that can affect liver profile.
Hypo/Hyper-thyroidism
Bypass surgeries
TPN (Total Parenteral Nutrition)