The Effect of Nicorandil on Rheumatoid Arthritis Patients

Официальное название

The Effect of Nicorandil on Disease Activity in Rheumatoid Arthritis Patients

Обзор

The aim of this clinical trial is to determine whether nicorandil works in minimizing disease severity in patients with rheumatoid arthritis. The study will also assess the safety and tolerability of nicorandil. The main questions it aims to answer are: * Could nicorandil improve disease severity and symptoms of rheumatoid arthritis? * Does nicorandil lower the number of times participants need to use pain relieve medications? * Does the nicorandil improve participants functionality and ability to carry out daily activity? * Does nicorandil correct disease-associated damage and inflammation? * What side effects do participants have when taking nicorandil? Researchers will compare nicorandil to a placebo (a look-alike substance that contains no drug) to see if nicorandil works to decrease symptoms and severity of rheumatoid arthritis. Participants will: * Take nicorandil or a placebo two times daily for 3 months * Visit the clinic once every month for checkups * Keep a diary of their symptoms and the number of times they use a pain reliever

Подробное описание

Rheumatoid arthritis (RA) is a progressive systemic inflammatory autoimmune disease mainly affecting joints. Adequate treatment and control are important to prevent disease progression and extra-articular complications. Nicorandil is a nicotinamide anti-anginal drug with a potent anti-ischemic, anti-hypoxic, anti-inflammatory and immunomodulatory characteristics that may be potentially effective in the management of autoimmune diseases. Therefore, nicorandil would be a candidate intervention based on previous clinical trial on non-RA patients and animal studies on RA models.

This randomized stratified double-blinded clinical trial will recruit 70 patients based on inclusion criteria. Patients will be randomized to either receive nicorandil 10 mg twice daily or placebo twice daily in addition to conventional treatment for RA for 3 months. The study will be carried out according to ethical considerations.

Patients will be evaluated on monthly bases. At baseline patient history, demographic data, medical and medication history will be documented through patient interview and medical records. At baseline and after completion of 3 months of treatment, investigator will evaluate the patient for treatment safety and efficacy. Evaluation will include disease activity, frequency for using analgesics, quality of life, level of inflammatory mediators, and cartilage integrity. Throughout the study, patient will be followed up closely for any reported adverse effect. At the end of the study, statistical analysis will be done using SPSS software package and the appropriate test will be used.

Вмешательства

• Препарат Nicorandil Oral Tablet
  Nicorandil 10 mg oral tablets will be taken as one tablet twice daily for 3 months (12 weeks).
• Препарат Placebo
  Placebo oral tablets will be taken as one tablet twice daily for 3 months (12 weeks).
• Препарат conventional synthetic antirheumatic drugs (cDMARDs)
  A single or combination of cDMARDs and dose depend on disease severity.

Первичные конечные точки

• Evaluation of treatment Efficacy [Срок оценки: At baseline and at the end of the study (3 months (12 weeks)).]

Вторичные конечные точки (1)

• Evaluation of quality of life (QOL) [Срок оценки: At baseline and at the end of the study (3 months (12 weeks)).]

Критерии участия

Критерии включения

• Adult (≥18 years).
• Confirmed diagnosis with RA according to ACR/EULAR 2010 criteria.
• Moderate to severe disease activity (DAS-28 ˃ 3.2).
• Stable on conventional treatment for at least 3 months.
• Adequate kidney and liver function.

Критерии исключения

• Other autoimmune diseases
• Poor patient compliance
• Malignancy or history of malignancy
• Pregnancy or lactation.
• Patients receiving bDMARDs or tsDMARDs.
• Hypersensitivity to nicorandil.
• Left ventricular heart failure or severe hypotension (SBP ˂100 mmHg).
• History of cardiogenic shock.
• History or active gastric ulcer.
• Use of drugs contraindicated with nicorandil (e.g., sildenafil, tadalafil, vardenafil, tricyclic antidepressants, or guanyl cyclase).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Ain Shams University — Cairo

Публикации

• Okasha AH, Hegab II, Seleem MA, Azzam AR, Ibrahim S, Ghalwash AA, El-Gohary RM. Effects of Fisetin and Nicorandil on adjuvant-induced rheumatoid arthritis in rats: Emerging role of TLR4/NF-kappaB-induced Pyroptosis, Nrf-2/HO-1, and OPG/RANKL pathways. Cytokine. 2025 Mar;187:156876. doi: 10.1016/j.cyto.2025.156876. Epub 2025 Jan 29. PMID 39884184
• Zong Y, Li J, Xu X, Xu X. Effects of nicorandil on systemic inflammation and oxidative stress induced by percutaneous coronary intervention in patients with coronary heart disease. J Int Med Res. 2021 Dec;49(12):3000605211058873. doi: 10.1177/03000605211058873. PMID 34871513
• Xu S, Cao X, Yu Z, He W, Pang Y, Lin W, Chen Z, Guo W, Lu X, Lin C. Nicorandil Inhibits Osteoclast Formation Base on NF-kappaB and p-38 MAPK Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss. Front Pharmacol. 2021 Sep 8;12:726361. doi: 10.3389/fphar.2021.726361. eCollection 2021. PMID 34566650
• Saad MA, El-Sahhar AE, Arab HH, Al-Shorbagy MY. Nicorandil abates arthritic perturbations induced by complete Freund's adjuvant in rats via conquering TLR4-MyD88-TRAF6 signaling pathway. Life Sci. 2019 Feb 1;218:284-291. doi: 10.1016/j.lfs.2019.01.002. Epub 2019 Jan 3. PMID 30611783
• Gaafar AGA, Messiha BAS, Abdelkafy AML. Nicorandil and theophylline can protect experimental rats against complete Freund's adjuvant-induced rheumatoid arthritis through modulation of JAK/STAT/RANKL signaling pathway. Eur J Pharmacol. 2018 Mar 5;822:177-185. doi: 10.1016/j.ejphar.2018.01.009. Epub 2018 Jan 11. PMID 29337196
• Quinonez-Flores CM, Gonzalez-Chavez SA, Pacheco-Tena C. Hypoxia and its implications in rheumatoid arthritis. J Biomed Sci. 2016 Aug 22;23(1):62. doi: 10.1186/s12929-016-0281-0. PMID 27549205

Идентификаторы

NCT: NCT07730723 · 2020110301REC480

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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