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Inflammopharmacology

, Volume 26, Issue 3, pp 737–745 | Cite as

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of β-d-mannuronic acid in rheumatoid arthritis patients

  • Hossein Ahmadi
  • Ahmad Reza Jamshidi
  • Farhad Gharibdoost
  • Mahdi Mahmoudi
  • Noushin Rastkari
  • Shayan Mostafaei
  • Mohammad Javad Fattahi
  • Mahdi Vojdanian
  • Salvatore Cuzzocrea
  • Bernd H. A. Rehm
  • Hidenori Matsuo
  • Mostafa Hosseini
  • Zahra Aghazadeh
  • Seyed Shahabeddin Mortazavi-Jahromi
  • Abbas Mirshafiey
Original Article

Abstract

Background

Following the potent efficacy of β-d-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy.

Method

The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety.

Results

There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient’s adverse events occurred during this study.

Conclusion

Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

Keywords

Mannuronic acid M2000 Rheumatoid arthritis NSAIDs DMARDs Immunosuppressive 

Notes

Acknowledgements

We would appreciate from the nurses and staffs of Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences (TUMS).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Hossein Ahmadi
    • 1
  • Ahmad Reza Jamshidi
    • 2
  • Farhad Gharibdoost
    • 2
  • Mahdi Mahmoudi
    • 2
  • Noushin Rastkari
    • 3
  • Shayan Mostafaei
    • 2
  • Mohammad Javad Fattahi
    • 1
    • 9
  • Mahdi Vojdanian
    • 2
  • Salvatore Cuzzocrea
    • 4
  • Bernd H. A. Rehm
    • 5
  • Hidenori Matsuo
    • 6
    • 7
  • Mostafa Hosseini
    • 8
  • Zahra Aghazadeh
    • 1
  • Seyed Shahabeddin Mortazavi-Jahromi
    • 1
    • 10
  • Abbas Mirshafiey
    • 1
  1. 1.Department of Immunology, School of Public HealthTehran University of Medical SciencesTehranIran
  2. 2.Rheumatology Research Center, Shariati HospitalTehran University of Medical SciencesTehranIran
  3. 3.Center for Air Pollution Research (CAPR), Institute for Environmental Research (IER)Tehran University of Medical SciencesTehranIran
  4. 4.Department of Chemical, Biological, Pharmaceutical and Environmental SciencesUniversity of MessinaMessinaItaly
  5. 5.Centre for Cell Factories and Biopolymers, Griffith Institute for Drug DiscoveryGriffith UniversityNathanAustralia
  6. 6.Department of Clinical ResearchNagasaki Kawatana Medical CenterNagasakiJapan
  7. 7.Department of NeurologyNagasaki Kawatana Medical CenterNagasakiJapan
  8. 8.Department of Epidemiology and Biostatistics, School of Public HealthTehran University of Medical SciencesTehranIran
  9. 9.Shiraz Institute for Cancer Research, School of MedicineShiraz University of Medical SciencesShirazIran
  10. 10.Department of Cellular and Molecular BiologyKish International Campus, University of TehranKishIran

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