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Coenzyme Q10 in Juvenile Idiopathic Arthritis Patients

Primary Purpose

Juvenile Idiopathic Arthritis

Status
Recruiting
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Coenzyme Q10
Placebo
Standard Regimen
Sponsored by
Nourhan Elsherif
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Juvenile Idiopathic Arthritis

Eligibility Criteria

3 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Pediatric Allergy, Immunology, Rheumatology Clinic, Children's Hospital, Ain Shams University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Coenzyme Q10 Group

Control Group

Arm Description

Patients will receive their JIA standard treatment plus 100 mg Coenzyme Q10 capsules daily for 3 months.

Patients will receive their standard JIA treatment plus placebo

Outcomes

Primary Outcome Measures

Disease Activity Evaluation
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: Physician's global rating of overall disease activity Parent/child ratings of well-being Counts of active joints assessed in 10 joints

Secondary Outcome Measures

Serum Malondialdehyde
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
Serum Tumor necrosis factor-alpha
serum samples will be withdrawn from each patient at baseline and after 3 months .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.
Safety of Coenzyme Q10
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
The Childhood Health Assessment Questionnaire (CHAQ)
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.
serum glutathione
an oxidative stress markers, glutathione will be assessed form patients sera at baseline and after 3 months. It will be measured using ELISA Kits

Full Information

First Posted
May 14, 2023
Last Updated
May 27, 2023
Sponsor
Nourhan Elsherif
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1. Study Identification

Unique Protocol Identification Number
NCT05871086
Brief Title
Coenzyme Q10 in Juvenile Idiopathic Arthritis Patients
Official Title
The Effect of Coenzyme Q10 Supplementation on the Clinical Outcome of Juvenile Idiopathic Arthritis Patients
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2023 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Nourhan Elsherif

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Juvenile Idiopathic Arthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Masking Description
Placebo will be given to patients in the control group
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Coenzyme Q10 Group
Arm Type
Experimental
Arm Description
Patients will receive their JIA standard treatment plus 100 mg Coenzyme Q10 capsules daily for 3 months.
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Patients will receive their standard JIA treatment plus placebo
Intervention Type
Dietary Supplement
Intervention Name(s)
Coenzyme Q10
Intervention Description
Coenzyme Q10 soft gelatin capsules daily for 3 months
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo Capsules
Intervention Type
Drug
Intervention Name(s)
Standard Regimen
Intervention Description
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
Primary Outcome Measure Information:
Title
Disease Activity Evaluation
Description
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: Physician's global rating of overall disease activity Parent/child ratings of well-being Counts of active joints assessed in 10 joints
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Serum Malondialdehyde
Description
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
Time Frame
3 months
Title
Serum Tumor necrosis factor-alpha
Description
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.
Time Frame
3 months
Title
Safety of Coenzyme Q10
Description
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
Time Frame
3 months
Title
The Childhood Health Assessment Questionnaire (CHAQ)
Description
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.
Time Frame
3 months
Title
serum glutathione
Description
an oxidative stress markers, glutathione will be assessed form patients sera at baseline and after 3 months. It will be measured using ELISA Kits
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nourhan N Elsherif
Phone
00201119793161
Email
nourhan.nasser18@pharma.asu.edu.eg
Facility Information:
Facility Name
Pediatric Allergy, Immunology, Rheumatology Clinic, Children's Hospital, Ain Shams University Hospital
City
Cairo
Country
Egypt
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
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Coenzyme Q10 in Juvenile Idiopathic Arthritis Patients

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