Ignite Creation Date:
2024-05-06 @ 7:02 PM
Last Modification Date:
2024-10-26 @ 2:59 PM
Study NCT ID:
NCT05871086
Status:
RECRUITING
Last Update Posted:
2023-05-31
First Post:
2023-05-14
Brief Title:
Coenzyme Q10 in Juvenile Idiopathic Arthritis Patients
Sponsor:
Nourhan Elsherif
Organization:
Ain Shams University
Study Overview
Official Title:
The Effect of Coenzyme Q10 Supplementation on the Clinical Outcome of Juvenile Idiopathic Arthritis Patients
Status:
RECRUITING
Status Verified Date:
2023-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Juvenile idiopathic arthritis JIA is the most common chronic rheumatological disorder in childhood of unknown cause and a major cause of functional disability Standard JIA treatment including nonsteroidal anti-inflammatory drugs NSAIDs corticosteroids methotrexate and biological agents have considerable adverse effects in addition to their high cost Despite the success of these treatment approaches patients may still have active disease with other sequelae from chronic inflammation and considerable morbidity that may negatively impact patients quality of life Therefore evaluating the potential benefit of alternative add-on anti-inflammatories and antioxidants might be a promising area for further research Coenzyme Q10 CoQ10 is a natural mitochondrial electron carrier and a powerful lipophilic antioxidant located in almost all cell membranes and plasma lipoproteins Several preclinical studies in animal models as well as clinical trials in adult patients with rheumatoid arthritis RA have demonstrated the beneficial effects of CoQ10 Results show that CoQ10 can reduce the oxidative and inflammatory status as well as clinical features that characterize this systemic autoimmune disease
Also CoQ10 has been used safely in children before and was well tolerated Thus the investigators would like to evaluate the effect of CoQ10 oral supplementation in pediatric JIA patients
Also CoQ10 has been used safely in children before and was well tolerated Thus the investigators would like to evaluate the effect of CoQ10 oral supplementation in pediatric JIA patients
Detailed Description:
Juvenile idiopathic arthritis JIA is the most common chronic rheumatological disorder in childhood of unknown etiology and a major cause of functional disability It has a prevalence rate of about 11000 worldwide The American College of Rheumatology ACR defines JIA as inflammation in one or more joints of unknown etiology with onset prior to age 16 years and a minimum of 6 weeks duration following the exclusion of other known causes of synovitis The International League of Associations for Rheumatology criteria classifies JIA into several different subgroups depending on the number of joints affected presence of extra-articular manifestations such as uveitis or glomerulonephritis systemic symptoms serology and genetic factors Peripheral arthritis is the common predominant clinical presentation among the various types The three main types of JIA are polyarticular oligoarticular and systemic JIA Therefore diagnosis of JIA depends on physical findings medical history and the exclusion of other diagnoses
The main hallmark of JIA is joint inflammation with bone resorption and tissue destruction
This chronic inflammation limits the daily activities and productivity of patients Interleukin-1 IL-1 IL-6 IL-17 and tumor necrosis factor-α TNF-α are inflammatory cytokines that play an important role in the pathogenesis prognosis disease activity and systemic features of JIA Additionally abnormal activation of T-cells B-cells natural killer NK cells dendritic cells DC macrophages and neutrophils contribute to the pathogenesis of JIA
All medications used to treat JIA including nonsteroidal anti-inflammatory drugs NSAIDs corticosteroids methotrexate and biological agents have considerable adverse effects in addition to the high cost of the biologics Also despite the success of these treatment approaches patients may still have active disease with other sequelae from chronic inflammation and considerable morbidity that may negatively impact patients quality of life Therefore evaluating the potential benefit of alternative add-on anti-inflammatories and antioxidants might be a promising area for further research
Coenzyme Q10 CoQ10 is a mitochondrial electron carrier and a powerful lipophilic antioxidant located in almost all cell membranes and plasma lipoproteins It can be found naturally and acquired from the diet or synthesized in-vivo by all cells of the body Various in-vitro and animal studies have demonstrated the antioxidant and anti-inflammatory effect of CoQ107 This has raised interest in its therapeutic potential against pathologies related to mitochondrial dysfunction and enhanced oxidative stress such as systemic autoimmune diseases
Several preclinical studies in animal models as well as clinical trials in patients with rheumatoid arthritis RA have demonstrated the beneficial effects of CoQ10 Results show that CoQ10 can reduce the oxidative and inflammatory status as well as clinical features that characterize this systemic autoimmune disease
In an attempt to understand the mechanisms by which CoQ10 exerts its anti-inflammatory and immunomodulatory effect Jhun et al conducted two studies on induced-arthritis mice models Their results showed that the mice that received CoQ10 showed significant decrease in RA severity Immunohistochemical analysis of synovial tissue showed that CoQ10 administration lead to significantly lower levels of proinflammatory cytokines such as IL-21 IL-1 IL-6 IL-17 TNF-α and vascular endothelial growth factor VEGF Also oxidative stress markers including nitrotyrosine and inducible nitric oxide synthase iNOS expression were significantly reduced in mice treated with CoQ10 CoQ10 also exhibited immunomodulatory effects on B and T-cells such as down-regulating IL-17 expression and Th17 cells population induced by inflammatory response
Furthermore Bauerova et al exhibited that the addition of CoQ10 to methotrexate MTX the most commonly prescribed anti-rheumatic agent suppressed the progression of RA in rats more than MTX alone The effect on oxidative stress and immunomodulation was shown through a decrease in the plasma levels of MDA and IL-1 respectively10 CoQ10 also proved that it has a protective role against hepatotoxicity caused by methotrexate This effect was shown in a study by Tawfik et al where liver function enzymes improved after the combination of CoQ10 with MTX in rats
To further elucidate the effect of CoQ10 supplementation two randomized clinical trials tested its use in adult rheumatoid arthritis patients Abdollahzad et al focused on the effect of CoQ10 on oxidative stress and inflammatory markers They registered a significant decrease in serum levels of MDA TNF-α and trending decrease in IL-6 Moreover no adverse drug events were observed confirming the safety and tolerability of CoQ10 With more focus on disease activity Nachvak et al reported significant decrease in Disease Activity Scores DAS-28 swollen joint count tender joint count and the visual analogue scale VAS scores accompanied by a reduction in erythrocyte sedimentation rate ESR and matrix metalloproteinase MMP-3 levels
Altogether evidence supports the beneficial effect of CoQ10 supplementation not only on inflammatory markers and oxidative stress but also on clinical features and presentation of arthritis patients Also CoQ10 has been used in doses up to 20 mgkgday in children safely and was well tolerated Up to date there is no published study to evaluate the use of CoQ10 in JIA Thus the investigators would like to evaluate the effect of CoQ10 oral supplementation as adjuvant therapy on the clinical outcomes in pediatric JIA patients
A prospective randomized controlled single blind clinical trial will be conducted on 60 Juvenile Idiopathic Arthritis JIA patients at the Pediatric Allergy Immunology Rheumatology Clinic Childrens Hospital Ain Shams University
At baseline caregivers of patients who are eligible will be educated about the study protocol and will be required to sign a written informed consent before enrollment in the study
Sixty patients will be recruited in the study and will be randomized to one of the following groups
A Intervention Coezyme Q10 Group 30 patients will receive their JIA standard treatment plus 100 mg Coenzyme Q10 capsules daily for 3 months
B Control Group 30 patients will receive their standard JIA treatment plus placebo
Blood samples will be withdrawn from patients at baseline and at the end of the 3 months trial period After 3 months of CoQ10 supplementation all the outcomes will be reassessed and reported to determine the effect on CoQ10 supplementation
The main hallmark of JIA is joint inflammation with bone resorption and tissue destruction
This chronic inflammation limits the daily activities and productivity of patients Interleukin-1 IL-1 IL-6 IL-17 and tumor necrosis factor-α TNF-α are inflammatory cytokines that play an important role in the pathogenesis prognosis disease activity and systemic features of JIA Additionally abnormal activation of T-cells B-cells natural killer NK cells dendritic cells DC macrophages and neutrophils contribute to the pathogenesis of JIA
All medications used to treat JIA including nonsteroidal anti-inflammatory drugs NSAIDs corticosteroids methotrexate and biological agents have considerable adverse effects in addition to the high cost of the biologics Also despite the success of these treatment approaches patients may still have active disease with other sequelae from chronic inflammation and considerable morbidity that may negatively impact patients quality of life Therefore evaluating the potential benefit of alternative add-on anti-inflammatories and antioxidants might be a promising area for further research
Coenzyme Q10 CoQ10 is a mitochondrial electron carrier and a powerful lipophilic antioxidant located in almost all cell membranes and plasma lipoproteins It can be found naturally and acquired from the diet or synthesized in-vivo by all cells of the body Various in-vitro and animal studies have demonstrated the antioxidant and anti-inflammatory effect of CoQ107 This has raised interest in its therapeutic potential against pathologies related to mitochondrial dysfunction and enhanced oxidative stress such as systemic autoimmune diseases
Several preclinical studies in animal models as well as clinical trials in patients with rheumatoid arthritis RA have demonstrated the beneficial effects of CoQ10 Results show that CoQ10 can reduce the oxidative and inflammatory status as well as clinical features that characterize this systemic autoimmune disease
In an attempt to understand the mechanisms by which CoQ10 exerts its anti-inflammatory and immunomodulatory effect Jhun et al conducted two studies on induced-arthritis mice models Their results showed that the mice that received CoQ10 showed significant decrease in RA severity Immunohistochemical analysis of synovial tissue showed that CoQ10 administration lead to significantly lower levels of proinflammatory cytokines such as IL-21 IL-1 IL-6 IL-17 TNF-α and vascular endothelial growth factor VEGF Also oxidative stress markers including nitrotyrosine and inducible nitric oxide synthase iNOS expression were significantly reduced in mice treated with CoQ10 CoQ10 also exhibited immunomodulatory effects on B and T-cells such as down-regulating IL-17 expression and Th17 cells population induced by inflammatory response
Furthermore Bauerova et al exhibited that the addition of CoQ10 to methotrexate MTX the most commonly prescribed anti-rheumatic agent suppressed the progression of RA in rats more than MTX alone The effect on oxidative stress and immunomodulation was shown through a decrease in the plasma levels of MDA and IL-1 respectively10 CoQ10 also proved that it has a protective role against hepatotoxicity caused by methotrexate This effect was shown in a study by Tawfik et al where liver function enzymes improved after the combination of CoQ10 with MTX in rats
To further elucidate the effect of CoQ10 supplementation two randomized clinical trials tested its use in adult rheumatoid arthritis patients Abdollahzad et al focused on the effect of CoQ10 on oxidative stress and inflammatory markers They registered a significant decrease in serum levels of MDA TNF-α and trending decrease in IL-6 Moreover no adverse drug events were observed confirming the safety and tolerability of CoQ10 With more focus on disease activity Nachvak et al reported significant decrease in Disease Activity Scores DAS-28 swollen joint count tender joint count and the visual analogue scale VAS scores accompanied by a reduction in erythrocyte sedimentation rate ESR and matrix metalloproteinase MMP-3 levels
Altogether evidence supports the beneficial effect of CoQ10 supplementation not only on inflammatory markers and oxidative stress but also on clinical features and presentation of arthritis patients Also CoQ10 has been used in doses up to 20 mgkgday in children safely and was well tolerated Up to date there is no published study to evaluate the use of CoQ10 in JIA Thus the investigators would like to evaluate the effect of CoQ10 oral supplementation as adjuvant therapy on the clinical outcomes in pediatric JIA patients
A prospective randomized controlled single blind clinical trial will be conducted on 60 Juvenile Idiopathic Arthritis JIA patients at the Pediatric Allergy Immunology Rheumatology Clinic Childrens Hospital Ain Shams University
At baseline caregivers of patients who are eligible will be educated about the study protocol and will be required to sign a written informed consent before enrollment in the study
Sixty patients will be recruited in the study and will be randomized to one of the following groups
A Intervention Coezyme Q10 Group 30 patients will receive their JIA standard treatment plus 100 mg Coenzyme Q10 capsules daily for 3 months
B Control Group 30 patients will receive their standard JIA treatment plus placebo
Blood samples will be withdrawn from patients at baseline and at the end of the 3 months trial period After 3 months of CoQ10 supplementation all the outcomes will be reassessed and reported to determine the effect on CoQ10 supplementation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None