Rheumatoid Arthritis (RA)
Conditions
Keywords
Rheumatoid Arthritis, Carnitine, anti-inflammatory, anti-oxidant, ACR50%, disease activity
Brief summary
This study aims to evaluate the effect of l-carnitine as add- on therapy for improving the outcome in rheumatoid arthritis patients.
Detailed description
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that affects joints of hand, wrist and foot. Its epidemiology is more pronounced in female to male in ratio 3:1 . Etiology of the disease is related to genetics and environmental factors that lead to formation of epitopes initiating autoimmune response . It is characterized by symmetrical polyarthritis in equal or more than 5 joints and it is known that long term inflammation leads to bone deformities, cartilage damage and synovitis. signs and symptoms include pain and tenderness of joints, morning stiffness for more than 30 minutes, fever, fatigue and weight loss . Also, there are extra-articular manifestations like rheumatoid nodules , interstitial lung disease and ocular manifestations like scleritis . Many treatment approaches in RA are based on anti- inflammatory, anti-oxidant and immune suppressive drugs mainly DMARDs. Up till now, there is no anti-inflammatory agent that is both safe and effective equivalent to DMARDs which are first line of treatment and that can be a scientific gap that should be filled in future research prespectives. L-Carnitine is a nutritional supplement that is used for enhancing performance in exercises, valproic acid toxicity, Rett syndrome and in case of secondary carnitine deficiency like in end stage renal disease (ESRD). Physiologically, it is synthesized from lysine and methionine. It is involved in energy production by assisting in transportation of long chain fatty acid into the mitochondria where they undergo beta oxidation for ATP production. Several studies have successfully proven that it has antioxidant effect by activating PPAR gamma which is transcription factor that directly increases expression of antioxidant enzymes like super oxide dismutase (SOD) . LC also have anti-inflammatory effect by acting on PPAR gamma that also inhibits Nf-KB pathway, thus decreasing release of inflammatory mediators. That was mentioned in literature done on inflammatory diseases like coronary artery disease and sepsis . The need for an add on therapy in RA increases to improve response to treatment and provide cost effectiveness benefit that opens the door for repurposing trials.
Interventions
DRUGCarnitine
It is a nutritional supplement with trade name Carnitol® in Egypt.
They are immunosuppressive drugs used to improve disease activity in Rheumatoid Arthritis patients . Conventional DMARDs include methotrexate (Imutrexate®) , leflunomide(Arthfree®) , hydroxychloroquine (plaquenil®) and sulfasalazine(colosalazine®) .
Sponsors
German University in Cairo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* age between 18-60 years old * diagnosed of rheumatoid arthritis according to 2010 American College of Rheumatology/European League Against Rheumatism criteria for at least 6 months * enrolled patients treated with one of more of conventional DMARDs for ≥ 6 months with stable dose for ≥ 1 month before start of the study * active RA despite conventional DMARDs treatment (DAS28 ESR more than or equal 3.2) * patient or legal representative should sign informed consent
Exclusion criteria
* pregnant or lactating female * patients with liver dysfunction (\>1.5x the upper limit of normal value for ALT & AST) * Patients with kidney dysfunction (serum creatinine more than 1.2 mg/dl) * Patients with any active infection or concurrent malignancy * patients with uncontrolled medical conditions or other rheumatic diseases * patients currently taking drugs that could interact with carnitine like: warfarin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in DAS28 ESR for both arms | From enrollment to the end of trial at 12 weeks | DAS 28-ESR is a score used to measure disease activity in RA patients. it is calculated using an equation where number of tender joints ( out of 28 joints) , number of swollen joints ( out of 28 joints) , patient assessment of disease activity ( using visual analogue scale from zero to 10) and ESR level are used as inputs to give DAS 28-ESR as output . the score will be measured to all participants both at baseline and at end of study. Higher scores indicate higher disease activity . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change in HAQ DI for both arms | From enrollment to the end of trial at 12 weeks | HAQ DI stands for health assessment questionnaire disability index that is used to reflect quality of life and functional disability where scores will vary from 0 to 3 and higher scores indicate more disability . A validated Arabic copy will be used and measured both at baseline and at end of trial. |
| change in TNF aplha for both arms | From enrollment to the end of trial at 12 weeks | anti inflammatory marker |
| proportion of patients achieving ACR50% in both arms | From enrollment to the end of trial at 12 weeks | It is a score used to measure disease activity in RA patients. ACR 50% is achieved when patient have 50% improvement in tender and swollen joints count and three out of the following five : ESR level , patient assessment of disease activity ( using visual analogue scale from 0 to 10) , physician assessment of disease activity ( using visual analogue scale from 0 to 10) , pain assessment ( using visual analogue scale from 0 to 10) and health assessment questionnaire . this outcome will be assessed at end of trial. |
| change in TAC for both arms | From enrollment to the end of trial at 12 weeks | It is an oxidative stress marker where higher values indicate better anti oxidant effect . |
| safety data for both arms | From enrollment to the end of trial at 12 weeks | A list of drug related adverse events will be reviewed by patients at each follow up visit ( at end of each month ) and at end of study. It will be expressed as nominal data ( number of patients experienced a certain adverse event versus number of those who don't) . |
| change in MDA for both arms | From enrollment to the end of trial at 12 weeks | It is an oxidative stress marker where higher values indicates more oxidative stress |
Countries
Egypt
Contacts
Primary ContactMariam Ehab, Master
Outcome results
None listed