The Effect of Nicorandil on Rheumatoid Arthritis Patients

NCT07730723 | Recruiting Phase 2

• 1 other identifier: 2020110301REC480
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Rheumatoid Arthritis (RA)

Keywords

Rheumatoid Arthritis (RA); Nicorandil; Inflammation; DAS-28; Disease activity; Autoimmune disease; HAQ-DI; Quality of life

Outcome Measures

Primary Outcomes (1)

• Evaluation of treatment Efficacy

  Treatment efficacy will be evaluated using disease activity score DAS-28 (ESR) and the frequency of using analgesics due to arthritis pain. Erythrocyte sedimentation rate (ESR) (mm/hr) will be measured using the Westergren method. Score interpretation: Score \<2.6 means disease remission, 2.6-3.2 means low disease activity, \>3.2-5.1 means moderate disease activity, and \>5.1 means high disease activity. After treatment intervention, a DAS-28 score reduction by 0.6 represents a moderate improvement, while a reduction more than 1.2 represents a major improvement. The frequency of using analgesics will be documented by patient using a diary sheet and weekly evaluation.

  At baseline and at the end of the study (3 months (12 weeks)).

Secondary Outcomes (1)

• Evaluation of quality of life (QOL)

  At baseline and at the end of the study (3 months (12 weeks)).

Other Outcomes (2)

• Evaluation of inflammation

  At baseline and at the end of the study (3 months (12 weeks)).

• Nicorandil safety assessment

  Monthly for 3 months (12 weeks).

Study Arms (2)

Nicorandil group

EXPERIMENTAL

Patients will receive the standard of conventional treatment (cDMARDs with/without corticosteroids) in addition to nicorandil 10 mg tablets twice daily for 3 months (12 weeks).

Drug: Nicorandil Oral Tablet; Drug: conventional synthetic antirheumatic drugs (cDMARDs)

Placebo group

PLACEBO COMPARATOR

Patients will receive the standard of conventional treatment (cDMARDs with/without corticosteroids) in addition to placebo tablets twice daily for 3 months (12 weeks).

Drug: Placebo; Drug: conventional synthetic antirheumatic drugs (cDMARDs)

Interventions

Nicorandil Oral Tablet DRUG

Nicorandil 10 mg oral tablets will be taken as one tablet twice daily for 3 months (12 weeks).

Also known as: Randil

Nicorandil group

Placebo DRUG

Placebo oral tablets will be taken as one tablet twice daily for 3 months (12 weeks).

Placebo group

conventional synthetic antirheumatic drugs (cDMARDs) DRUG

A single or combination of cDMARDs and dose depend on disease severity.

Also known as: methotrexate, leflunomide, sulfasalazine, hydroxychloroquine

Nicorandil group; Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain Shams University Hospitals

Cairo, Abbasia, Egypt

RECRUITING

Related Publications (6)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

Related Links

• Related Info
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MeSH Terms

Conditions

Arthritis, Rheumatoid; Inflammation; Autoimmune Diseases

Interventions

Nicorandil; Methotrexate; Leflunomide; Sulfasalazine; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitrates; Organic Chemicals; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Isoxazoles; Azoles; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Chloroquine; Aminoquinolines; Quinolines

Study Officials

• Nagwa A. Sabri, Professor

  Prof. of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University

  STUDY DIRECTOR

• May A. Shawky, Assoc. Prof.

  Assoc. Prof. of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University

  STUDY DIRECTOR

Central Study Contacts

Sondos S. Saleh, Assistant Lecturer

CONTACT

+201153495055; sondos.sherif.ismail@pharma.asu.edu.eg

Marwa A. Al-Asfahani, Lecturer

CONTACT

+201120029192; sondos.sherif.ismail@pharma.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer in Clinical Pharmacy Department

Study Record Dates

• First Submitted: July 23, 2026
• First Posted: July 28, 2026
• Study Start: September 6, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)