Tacrolimus Combined With Low-dose Prednisone for Treatment of Myasthenia Gravis
- Conditions
- Myasthenia Gravis
- Interventions
- Registration Number
- NCT04768465
- Lead Sponsor
- Da, Yuwei, M.D.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 160
-
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:
- positive clinical response to acetylcholinesterase inhibitor
- positive AchR-Ab or MuSK-Ab testing
- 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
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Tacrolimus monotherapy Pyridostigmine, Tacrolimus MG patients are treated with tacrolimus as initial immune monotherapy. Symptomatic treatment like pyridostigmine bromide can be added to relieve symptoms (≤480mg/d). Combined Immunotherapy Pyridostigmine, Prednisone, Tacrolimus 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).
- Primary Outcome Measures
Name Time Method Change of MG-specific Activities of Daily Living scale (MG-ADL) from Baseline 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.
- Secondary Outcome Measures
Name Time Method Change of Myasthenia Gravis Quantity-of-Life Scale (MG-QoL15) from Baseline 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.
Changes of MG-ADL subscores from baseline 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.
Time to achievement of minimal manifestations (MMS) or better 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).
Change of Quantitative Myasthenia Gravis (QMG) Scores from Baseline 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).
Withdrawal 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.
Time to achievement of Patient-Acceptable Symptom States 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.
Serum IL-2 level 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.
Treatment Failure 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.
Trial Locations
- Locations (1)
Yuwei Da
🇨🇳Beijing, Beijing, China