Coenzyme Q10 in Juvenile Idiopathic Arthritis Patients

May 27, 2023 updated by: Nourhan Elsherif

The Effect of Coenzyme Q10 Supplementation on the Clinical Outcome of Juvenile Idiopathic Arthritis Patients

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 1/1000 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 CoQ10.7 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, respectively.10 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 mg/kg/day 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, Children's 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 Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
      • Cairo, Egypt
        • Recruiting
        • Pediatric Allergy, Immunology, Rheumatology Clinic, Children's Hospital, Ain Shams University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pediatric patients (<16 years old)
  • Diagnosed with active JIA according to the American College of Rheumatology (ACR) 2019 guideline.
  • Patients with peripheral oligo or polyarthritis.
  • With more than 6-month disease duration
  • Participants who have inadequate response to at least one first line standard therapy.
  • Patients who have been receiving a stable treatment regimen for the past 3 months

Exclusion Criteria:

  • Patients with active systemic JIA
  • Patients presenting with complications (such as amyloidosis, uveitis, or glomerulonephritis)
  • Patients with other chronic autoimmune disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Coenzyme Q10 Group
Patients will receive their JIA standard treatment plus 100 mg Coenzyme Q10 capsules daily for 3 months.
Dietary supplement: Coenzyme Q10
Coenzyme Q10 soft gelatin capsules daily for 3 months
Drug: Standard Regimen

Patients may be receiving any of these commonly used JIA treatments including:

  • Ibuprofen - 30 to 40 mg/kg/day in 3 to 4 divided doses
  • Diclofenac - 2 to 3 mg/kg/day in divided doses 2 to 3 times daily
  • Methotrexate - Initial: 10 to 15 mg/m2 once weekly; adjust gradually up to 20 to 30 mg/m2 once weekly
  • Leflunomide - Weight based, 10-20 mg once daily
  • Sulfasalazine - 30 to 50 mg/kg/day in 2 divided doses
  • Etanercept - 0.8 mg/kg/dose once weekly
  • Adalimumab - Weight based, 10-40 mg every other week
Placebo Comparator: Control Group
Patients will receive their standard JIA treatment plus placebo
Drug: Standard Regimen

Patients may be receiving any of these commonly used JIA treatments including:

  • Ibuprofen - 30 to 40 mg/kg/day in 3 to 4 divided doses
  • Diclofenac - 2 to 3 mg/kg/day in divided doses 2 to 3 times daily
  • Methotrexate - Initial: 10 to 15 mg/m2 once weekly; adjust gradually up to 20 to 30 mg/m2 once weekly
  • Leflunomide - Weight based, 10-20 mg once daily
  • Sulfasalazine - 30 to 50 mg/kg/day in 2 divided doses
  • Etanercept - 0.8 mg/kg/dose once weekly
  • Adalimumab - Weight based, 10-40 mg every other week
Other: Placebo
Placebo Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Activity Evaluation
Time Frame: 3 months

Clinical efficacy will be assessed by calculating the Clinical Juvenile Arthritis Disease Activity Score (cJADAS-10) at baseline and at the end of the 3-month trial period.

The cJADAS is computed by assessing the following variables:

  1. Physician's global rating of overall disease activity
  2. Parent/child ratings of well-being
  3. Counts of active joints assessed in 10 joints
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Malondialdehyde
Time Frame: 3 months
an oxidative stress markers, Malondialdehyde (MDA) will be assessed form patients sera at baseline and after 3 months. It will be measured using ELISA Kits
3 months
Serum Tumor necrosis factor-alpha
Time Frame: 3 months
serum samples will be withdrawn from each patient at baseline and after 3 months . Tumor necrosis factor-alpha will be measured using an ELISA Kit.
3 months
Safety of Coenzyme Q10
Time Frame: 3 months
CoQ10 safety will be monitored by asking the parents through interviews and phone calls every 2 weeks about the occurrence of any of the following side effects: abdominal discomfort, loose stools, headache, nausea, and vomiting. assessment will be done every 2 weeks
3 months
serum glutathione
Time Frame: 3 months
an oxidative stress markers, glutathione will be assessed form patients sera at baseline and after 3 months. It will be measured using ELISA Kits
3 months
The Childhood Health Assessment Questionnaire (CHAQ)
Time Frame: 3 months

The Childhood Health Assessment Questionnaire (CHAQ) assesses functional ability in 8 domains of physical function (30 items) for children (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and activities). Each item is scored on a four-point scale ranging from 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), 3 (unable to do). The mean score of the eight domains finally makes up the disability index and ranges from 0 (no disability) to 3 (disabled).

Quality of life scores will be performed for patients at baseline and at the end of the 3-months trial period.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nourhan Elsherif

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2023

Primary Completion (Estimated)

December 1, 2023

Study Completion (Estimated)

December 1, 2023

Study Registration Dates

First Submitted

May 14, 2023

First Submitted That Met QC Criteria

May 14, 2023

First Posted (Actual)

May 23, 2023

Study Record Updates

Last Update Posted (Actual)

May 31, 2023

Last Update Submitted That Met QC Criteria

May 27, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACUCFPASURHDIRB2020110301#169

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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