Tacrolimus Combined With Low-dose Prednisone for Treatment of Myasthenia Gravis
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|ClinicalTrials.gov Identifier: NCT04768465|
Recruitment Status : Recruiting
First Posted : February 24, 2021
Last Update Posted : February 24, 2021
|Condition or disease||Intervention/treatment|
|Myasthenia Gravis||Drug: Pyridostigmine, Prednisone, Tacrolimus Drug: Pyridostigmine, Tacrolimus|
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||160 participants|
|Target Follow-Up Duration:||6 Months|
|Official Title:||Effectiveness and Safety of Tacrolimus Combined With Low-dose Prednisone for Treatment of Myasthenia Gravis: A Real-world Study|
|Actual Study Start Date :||January 1, 2021|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||October 31, 2024|
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.
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.
- 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.
- 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).
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
Biospecimen Retention: Samples With DNA
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 ClinicalTrials.gov identifier (NCT number): NCT04768465
|Contact: Yuwei Da, M.D.||email@example.com|
|Contact: Yuwei Da, M.D.||firstname.lastname@example.org|
|Beijing, Beijing, China, 100053|
|Contact: Yuwei Da, M.D. 00-86-010-83198492 email@example.com|
|Study Chair:||Yuwei Da, M.D.||Xuanwu Hospital, Beijing|