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Comparison of Clinical Effects of Azathioprine and Rituximab NMO-SD Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03002038
Recruitment Status : Completed
First Posted : December 23, 2016
Last Update Posted : January 2, 2017
Information provided by (Responsible Party):
Vahid Shaygannejad, Isfahan University of Medical Sciences

Brief Summary:
The purpose of this study is to compare annual relapse rate, expanded disability status scale, and side effects of azathioprine and rituximab in patients with neuromyelitis optica spectrum disorder during a one year follow up through a randomized clinical trial.

Condition or disease Intervention/treatment Phase
Neuromyelitis Optica Spectrum Disorder Drug: Azathioprine Drug: Rituximab Phase 2 Phase 3

Detailed Description:

Neuromyelitis Optica Spectrum Disorder (NMO-SD) is a recurrent inflammatory demyelinating disease affecting the central nervous system. The disease is clinically recognized by optic neuritis and transverse myelitis and is associated with high risk of mortality. Each attack worsens patients' disability. This means that after 5 years of the disease onset, half of patients need to use wheelchair and approximately 50% of them become blind.

Considering that the disease can be disabling for patients, the maintenance treatment should be applied in addition to treatment of acute attacks, in order to prevent future recurrences. Acute attacks are usually treated with high doses of intravenous corticosteroids. Plasmapheresis is also used when patients fail to response to corticosteroids. B lymphocyte inhibitors are used as the maintenance therapy in these patients. First line therapeutic medications include azathioprine and rituximab which are being recommended for long term therapy and second line medications include methotrexate and mycophenolate mofetil.

Azathioprine is an immune-modulatory agent which is available in the oral form and don't require hospitalization to be administered, however, because of side effects such as bone marrow suppression and hepatotoxicity, periodic check of blood cells and liver enzymes are needed. Rituximab is a cluster of differentiation antigen 20 inhibitor which leads to decreased B lymphocytes and antibody in patients. This medication is only available in the injectable form and needs hospitalization to be administered. Close monitory is needed during the administration considering severe side effects such as allergic reactions and respiratory distress. However, laboratory tests are not needed in patients taking rituximab although it is more expensive than azathioprine. No clinical trial has been performed previously to compare clinical efficacy of these two drugs in NMO-SD patients. Therefore, we aimed to compare their efficacy through a randomized clinical trial.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Comparison of Annual Relapse Rate, Expanded Disability Status Scale, and Side Effects Between Azathioprine and Rituximab in Patients With Neuromyelitis Optica Spectrum Disorders
Study Start Date : September 2015
Actual Primary Completion Date : November 2016
Actual Study Completion Date : December 2016

Arm Intervention/treatment
Experimental: Azathioprine
Patients in this group will receive 50 mg of azathioprine, two times each day and gradually increased to maximum dose of 3 g daily with the aim of lymphocytes count less than 1500.
Drug: Azathioprine
Patients are started with Azathioprine 50 mg tablets, taken orally twice a day. The medication dose is increased gradually with the aim of lymphocytes count bellow 1500 and to the maximum dose of 3 g Azathioprine per day. Cell blood count is checked once a week in the first month of treatment, once every two weeks in the second month of treatment, and monthly in the third month of treatment to make decision about medication dose.
Other Name: Azathioprine Mehrdaru®

Experimental: Rituximab
Patients in this group will receive 1g of Rituximab in 500 cc normal saline serum through intravenous infusion with two weeks intervals (as one course) and each course of treatment is repeated every 6 months.
Drug: Rituximab
Patients will receive 1 g of Rituximab (two vials of RediTux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion and this will be repeated two weeks later. This cycle will be repeated every 6 months.
Other Name: RediTux®

Primary Outcome Measures :
  1. Annual Relapse Rate [ Time Frame: one year ]
    annual relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.

Secondary Outcome Measures :
  1. Expanded Disability Status Scale [ Time Frame: one year ]
    expanded disability status scale will be measured in the baseline and after 12 months of intervention

Other Outcome Measures:
  1. Adverse Drug Reactions [ Time Frame: one year ]
    adverse drug reactions will be observed closely and reported during the intervention. We will compare the number of adverse drug reactions in two groups. Also, adverse drug reactions will be described by details in each group.

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of neuromyelitis optica spectrum disorder based on the recent guidelines in 2015
  • Expanded disability status scale between 0 and 7
  • Age between 18 and 50 years old

Exclusion Criteria:

  • Pregnancy or lactation during the study
  • Deciding to leave the study by patient
  • Lack of consent to enter the study
  • Lack of cooperation for follow up
  • Severe side effect of the medication
  • Treatment with other immunosuppressant medications (including but not limited to cyclophosphamide, mycophenolate mofetil, methotrexate, others) within two months before intervention
  • Taking any other immunosuppressant or other type of medication (including herbal drugs) without permission of the physician during the study.
  • Presence of other autoimmune disease (including but not limited to Behcet disease, systemic lupus erythematosus, rheumatoid arthritis, and others)
  • Presence of liver disorders
  • Presence of hematologic disorders
  • Presence of heart failure
  • Receipt of a live vaccine within 4 weeks prior to intervention
  • Previous treatment with Azathioporine or Rituximab
  • History of HIV, hepatitis B, or hepatitis C
  • Ongoing daily steroid use
  • History of severe allergic or anaphylactic reaction to monoclonal antibodies

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03002038

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Iran, Islamic Republic of
Kashani Hospital
Isfahan, Iran, Islamic Republic of, 8174673461
Sponsors and Collaborators
Isfahan University of Medical Sciences
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Study Chair: Vahid Shaygannejad, M.D. Department of Neurology, School of Medicine, Isfahan University of Medical Sciences

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Vahid Shaygannejad, Associate Professor of Neurology, Isfahan University of Medical Sciences Identifier: NCT03002038     History of Changes
Other Study ID Numbers: 395275
First Posted: December 23, 2016    Key Record Dates
Last Update Posted: January 2, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: We may share the individual participant data (anonymously) on request of the journal publishing the study report.
Keywords provided by Vahid Shaygannejad, Isfahan University of Medical Sciences:
neuromyelitis optica spectrum disorder
clinical trial
annual relapse rate
expanded disability status scale
Additional relevant MeSH terms:
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Neuromyelitis Optica
Myelitis, Transverse
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Neuritis
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents