Tacrolimus Combined With Low-dose Prednisone for Treatment of Myasthenia Gravis

February 21, 2021 updated by: Da, Yuwei, M.D.

Effectiveness and Safety of Tacrolimus Combined With Low-dose Prednisone for Treatment of Myasthenia Gravis: A Real-world Study

This study is designed to evaluate the effectiveness and safety of tacrolimus combined with low-dose prednisone in the management of myasthenia gravis patients, compared to tacrolimus as initial immune monotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single center, observational real-world study recruiting myasthenia gravis patients from Neurology Departments of Xuanwu Hospital, aiming to compare effectiveness and safety of 2 different inmunotherapy for MG. The study plans to recruit 160 MG participants and divides into 2 treatment groups according to physician's judgment and preferences of patients, one is combined immunotherapy group in which tacrolimus added with low-dose prednisone (0.25mg/kg/d), and the other is tacrolimus monotherapy group. Both groups can be treated with pyridostigmine to relieve symptoms. Patients are followed up at 1, 3 and 6 month after treatment initiation to assess the efficacy of both regimen. The primary outcome is the change of MG-ADL scores. Also, liver and renal functions are tested to monitor any side effects. Patients' clinical records are uploaded to an online database.

Study Type

Observational

Enrollment (Anticipated)

160

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100053
        • Recruiting
        • Yuwei Da

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with Myasthenia Gravis

Description

Inclusion Criteria:

  • Age ≥18

  • Clinical Diagnosis of MG is confirmed based on typical clinical features of fluctuating muscle weakness, with at least 1 of the following supporting evidence:

    1. positive clinical response to acetylcholinesterase inhibitor
    2. positive AchR-Ab or MuSK-Ab testing
    3. decrement >10% in repetitive nerve stimulations study (RNS) or increased jitter on single-fibre electromyography (SFEMG)
  • MGFA clinical classification: I - IV
  • Baseline MG-ADL ≥ 3
  • Disease course from onset to enrollment ≤ 12 months
  • Cooperation to followup
  • Written informed consent

Exclusion Criteria:

  • Initiation of immunosuppressant for MG prior to screening, including Prednisone, Methylprednisolone, Azathioprine, Methotrexate, Cyclosporine A, Mycophenolate Mofetil, Tacrolimus and Cyclophosphamide
  • Treatment of immunosuppressant for other concomitant disease 6 months prior to recruitment
  • Rapid immunosuppressive treatments like Intravenous immunoglobulin or plasma exchange 1 month prior to recruitment
  • Thymectomy within 3 months prior to Screening
  • Concomitant chronic degenerative, psychiatric, or neurologic disorder that can cause weakness or fatigue
  • Consciousness, dementia or schizophrenia
  • Pregnancy or lactation, unwillingness to avoid pregnancy
  • Uncontrolled hypertension or diabetes, Liver or kidney dysfunction, Cataract, Severe osteoporosis, Femoral head necrosis; Hyperkalemia, HIV, Acute or chronic infection
  • Other conditions that would preclude participation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Combined Immunotherapy

MG patients are treated with tacrolimus combined with low-dose prednisone (0.25mg/kg/d).

Symptomatic treatment like pyridostigmine bromide can be added to relieve symptoms (≤480mg/d).
Drug: Pyridostigmine, Prednisone, Tacrolimus
Dose of tacrolimus should be initiated based on CYP3A5*3 polymorphism and adjusted to achieve blood trough concentration of 4.8-10.0 ng/ml. Prednisone is administrated with an initial dose of 0.25mg/kg/d and started to tamper with the achievement of MMS or the presence of any intolerable side effects. The rate of tampering is considered by the physician, usually no more than 5mg/month. If the participants failed to maintain MMS, dose of prednisone should be increased 5mg/week to 0.25mg/kg/d and maintained until MMS reached again. After MMS sustained for 1 month, prednisone dose would be tapered again with 2.5mg/month. Calcium and potassium supplements and gastric mucosa protectors could be addressed to avoid any adverse effects of prednisone. Treatment regimens are determined based on the physician's judgment and preferences of the patients. This study was observational and do not change the clinical course of patients.
Other Names:
  • Pyridostigmine Bromide
  • Deltacortone/Meticorten/Prednisone Acetate Tablets
  • Prograf/FK506
Tacrolimus monotherapy
MG patients are treated with tacrolimus as initial immune monotherapy. Symptomatic treatment like pyridostigmine bromide can be added to relieve symptoms (≤480mg/d).
Drug: Pyridostigmine, Tacrolimus
Dose of tacrolimus should be initiated based on CYP3A5*3 polymorphism and adjusted to achieve blood trough concentration of 4.8-10.0 ng/ml. Treatment regimens are determined based on the physician's judgment and preferences of the patients. This study was observational and do not change the clinical course of patients.
Other Names:
  • Pyridostigmine Bromide
  • Prograf/FK506

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of MG-specific Activities of Daily Living scale (MG-ADL) from Baseline
Time Frame: Baseline, 1 month, 3 months, 6 months
The MG-ADL is an 8-item scale to assess symptoms of myasthenia gravis patients obtained by summing the responses to each individual item (Grades: 0,1,2,3). The score ranges from 0 to 24.
Baseline, 1 month, 3 months, 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to achievement of minimal manifestations (MMS) or better
Time Frame: From Baseline to 6 months
The time duration from treatment initiation to the achievement of MMS or better. Clinical statuses of patients are assessed and categorized according to Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS). MM or better includes Minimal Manifestation (MM), Pharmacologic Remission (PR) or Complete Remission (CR).
From Baseline to 6 months
Time to achievement of Patient-Acceptable Symptom States
Time Frame: From Baseline to 6 months
The Patient-Acceptable Symptom States question is a simple yes or no query that asked: "Considering all the ways you are affected by Myasthenia, if you had to stay in your current state for the next month, would you say that your current disease state status is satisfactory?" This question reflects the patients assessment of their own health.
From Baseline to 6 months
Change of Quantitative Myasthenia Gravis (QMG) Scores from Baseline
Time Frame: Baseline, 1 month, 3 months, 6 months
The QMG is a 13-item scale which measures ocular, bulbar, limb function and respiratory function. The total score ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits) obtained by summing the responses to each individual item (None=0, Mild=1, Moderate=2, Severe=3).
Baseline, 1 month, 3 months, 6 months
Change of Myasthenia Gravis Quantity-of-Life Scale (MG-QoL15) from Baseline
Time Frame: Baseline, 1 month, 3 months, 6 months
The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with myasthenia gravis (MG)-related dysfunction. MG-QOL15 evaluates patients' aspects about physical status, social adaptation and mental well-being.
Baseline, 1 month, 3 months, 6 months
Changes of MG-ADL subscores from baseline
Time Frame: Baseline, 1 month, 3 months, 6 months
Subscores of ADL items can reflect patients' assessment about different MG-related dysfunctions, including ptosis, diplopia, talking, chewing, swallowing, breathing and limbs function.
Baseline, 1 month, 3 months, 6 months
Serum IL-2 level
Time Frame: Baseline, 1 month, 3 months, 6 months
Tacrolimus exerts its immunosuppressive effect by inhibiting the early phase gene expression during T-cell activation, including the pro-inflammation IL-2 gene. Thus serum IL-2 is tested as a target of tacrolimus and also a marker of in vivo auto-immune status after treatment.
Baseline, 1 month, 3 months, 6 months
Treatment Failure
Time Frame: Baseline to 6 months
Treatment failure is defined as discontinuation of tacrolimus therapy in patients who failed to achieve MMS or better or suffered from exacerbations (MG-ADL or QMG scores increase 50%) or myasthenia crisis.
Baseline to 6 months
Withdrawal
Time Frame: Baseline to 6 months
Participants quit the clinical trial for any reason including unsatisfied response, economic burden or poor compliance to treatment protocol. Patients may quit at any time they want.
Baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Da, Yuwei, M.D.

Investigators

  • Study Chair: Yuwei Da, M.D., Xuanwu Hospital, Beijing

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Anticipated)

December 31, 2023

Study Completion (Anticipated)

October 31, 2024

Study Registration Dates

First Submitted

February 21, 2021

First Submitted That Met QC Criteria

February 21, 2021

First Posted (Actual)

February 24, 2021

Study Record Updates

Last Update Posted (Actual)

February 24, 2021

Last Update Submitted That Met QC Criteria

February 21, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1.0

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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