Clinical trial NCT06640309: The Effect of Nicotinamide on the Clinical Outcome of Rheumatoid Arthritis Patients
Official title: The Effect of Nicotinamide on the Clinical Outcome of Rheumatoid Arthritis Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Nicotinamide
Quality of life
DAS-28
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2024-10-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective randomized controlled interventional parallel open label study.
Primary purpose: TREATMENT

Brief summary: A randomized controlled interventional study to evaluate the efficacy and safety of nicotinamide supplementation in rheumatoid arthritis patients receiving conventional synthetic disease modifying anti-rheumatic drugs.

Detailed description: Study design:

A prospective randomized controlled interventional parallel open label study.

Patient randomization:

All patients fulfilling the inclusion criteria will be randomly assigned by simple randomization into either nicotinamide group or control group as follows:

* Nicotinamide group: consists of thirty-five patients who will receive nicotinamide 1000mg tablet once daily.in addition to their conventional therapy.
* Control group: consists of thirty-five patients who will receive their conventional therapy only.

Methodology:

At baseline, the following will be obtained through patients' interview:

1. Demographic data.
2. Medical history and comorbidities.
3. The disease activity; identified through patients' physical examination and serum C-Reactive Protein (CRP) levels as prerequisites for Disease Activity Score-28 (DAS-28-CRP).
4. The disease duration.
5. Current medications history.

Evaluation of the efficacy and safety of nicotinamide will be assessed at baseline and after three months through:

1. Blood sampling will be collected from patients for serum CRP , Erythrocyte sedimentation rate (ESR) and analysis of Interleukin-10 .These samples will be directly centrifuged at 1000 x g for fifteen minutes and then plasma will be separated and collected in capped test tubes, then will be stored at -80 °C until analysis.

   Interleukin-10 serum level will be measured using an Enzyme Linked Immunosorbent Assay (ELISA) technique.
2. Disease Activity will be calculated based on tender joint count (TJC) and swollen joint count (SJC) following the assessment of twenty-eight joints, serum CRP level, and the patient's global health assessment (PGA) on a scale from zero to one hundred. The score will be calculated using the following equation:

   DAS-28-CRP = 0.56\* √(TJC28) + 0.28\* √(SJC28) + 0.36\*ln (CRP + 1) +0.014\*(PGA) + 0.96
3. Patient's QOL will be assessed by using the Health Assessment Questionnaire-Disability Index (HAQ-DI)
4. Patients will be educated about the side effects and/or adverse effects of nicotinamide, where, safety and tolerability will be monitored by reporting the incidence of any side effect and /or adverse effect such as stomach upset, flatulence, dizziness, headache, and rash.

Blood samples will be collected for complete blood count (CBC), alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (Scr.) levels analysis to monitor adverse effects of conventional synthetic disease-modified antirheumatic (csDMARDs) drugs and nicotinamide.

Eligibility criteria: Inclusion Criteria:

* Adult patients (18-65 years).
* Patients with a diagnosis of established rheumatoid arthritis.
* Patients presenting with moderate to high disease activity identified as disease activity score-28 based on C-reactive protein levels (DAS-28-CRP) \>3.2.
* Receiving stable regimen of one or more conventional disease modifying antirheumatic drugs for at least the past three months.
* Patients willing to sign an informed consent.

Exclusion Criteria:

* Patients with a known history of hypersensitivity or drug allergies to nicotinamide
* Patients receiving nicotinamide for any other indications.
* Receiving any dosage forms/ dosage regimen of vitamin B3 supplementation
* Receiving biologic disease modified antirheumatic drugs therapy.
* Impaired liver functions (liver transaminases level ≥ three times upper normal limits).
* Impaired kidney functions (estimated glomerular filtration rate (eGFR) \< 30 ml/min)
* Pregnancy and lactation.
* Patients with other auto-immune diseases.

Primary outcomes:
measure: Disease severity assessment using DAS-28 -CRP
timeFrame: At baseline and after three months.
Secondary outcomes:
measure: Serum Interleukin-10
timeFrame: At baseline and after three months.
measure: Detection of any change in inflammatory markers
timeFrame: At baseline and after three months.
measure: Quality of Life (QOL) questionnaire
timeFrame: At baseline and after three months.
measure: Safety and tolerability of Nicotinamide
timeFrame: Three months.
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University Hospitals
Study officials:
affiliation: Professor and head of department of Clinical Pharmacy at Faculty of Pharmacy Ain Shams University
name: Lamia El wakeel, Professor
role: STUDY_DIRECTOR
affiliation: Assistant professor of Clinical Pharmacy, Ain Shams University-Faculty of Pharmacy
name: May Ahmed, Asst. professor
role: STUDY_DIRECTOR
References:
citation: Kamat JP, Devasagayam TP. Nicotinamide (vitamin B3) as an effective antioxidant against oxidative damage in rat brain mitochondria. Redox Rep. 1999;4(4):179-84. doi: 10.1179/135100099101534882.
citation: Miesel R, Kurpisz M, Kroger H. Modulation of inflammatory arthritis by inhibition of poly(ADP ribose) polymerase. Inflammation. 1995 Jun;19(3):379-87. doi: 10.1007/BF01534394.
citation: Ungerstedt JS, Blomback M, Soderstrom T. Nicotinamide is a potent inhibitor of proinflammatory cytokines. Clin Exp Immunol. 2003 Jan;131(1):48-52. doi: 10.1046/j.1365-2249.2003.02031.x.