The Effect of Nicotinamide on the Clinical Outcome of Rheumatoid Arthritis Patients (NAM&RA)

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.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Nicotinamide Tablet; Drug: conventional synthetic antirheumatic 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.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sara A. Raslan, Bachelor; Phone Number: +20 1020145174; Email: Sarah.raslan@pharma.asu.edu.eg
• Study Contact Backup: Name: Dalia Abdelmohsen, Professor; Phone Number: +20 100 1580007; Email: d_mohsen@hotmail.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Ain shams university hospitals
    • Contact: Dalia Abdelmohsen, Professor; Phone Number: +20 100 1580007; Email: d_mohsen@hotmail.com
    • Principal Investigator: Sara Raslan, Bachelor
    • Sub-Investigator: Dalia Abdelmohsen, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: control group; Patients will receive their conventional therapy only.	Drug: conventional synthetic antirheumatic drugs; methotrexate- leflunomide- sulfasalazine- hydroxychloroquine
Experimental: Nicotinamide group; Patients will receive nicotinamide 1000mg tablet once daily.in addition to their conventional therapy for three months.	Drug: Nicotinamide Tablet; Nicotinamide is anti-inflammatory and antioxidant.; Drug: conventional synthetic antirheumatic drugs; methotrexate- leflunomide- sulfasalazine- hydroxychloroquine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease severity assessment using DAS-28 -CRP	DAS-28-CRP at baseline and at end of study, which will be calculated based on tender joint count (TJC) and swollen joint count (SJC) following the assessment of twenty-eight joints (figure 1) , 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: (CASTREJÓN et al., 2010) DAS-28-CRP = 0.56* √(TJC28) + 0.28* √(SJC28) + 0.36*ln (CRP + 1) +0.014*(PGA) + 0.96	At baseline and after three months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Interleukin-10	Venous blood samples will be collected from patients at baseline and at the end of the study (three months). Blood 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 at baseline and after three months of study period using an ELISA technique according to the manufacturer's protocol.	At baseline and after three months.
Detection of any change in inflammatory markers	Serum C-reactive protein and Erythrocyte sedimentation rate.	At baseline and after three months.
Quality of Life (QOL) questionnaire	Patient's QOL will be assessed by using the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline and after three months. It assesses patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities	At baseline and after three months.
Safety and tolerability of Nicotinamide	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.	Three months.

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Study Director: Lamia El wakeel, Professor, Professor and head of department of Clinical Pharmacy at Faculty of Pharmacy Ain Shams University; Study Director: May Ahmed, Asst. professor, Assistant professor of Clinical Pharmacy, Ain Shams University-Faculty of Pharmacy

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Quality of life; Rheumatoid Arthritis; DAS-28; Nicotinamide
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin; Antirheumatic Agents
• Other Study ID Numbers: NAM/RA/1223

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