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

NCT04768465 | Unknown FDA Drug

• 1 other identifier: 1.0
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

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.

Conditions

Myasthenia Gravis

Keywords

myasthenia gravis; treatment; tacrolimus; low-dose prednisone

Outcome Measures

Primary Outcomes (1)

• Change of MG-specific Activities of Daily Living scale (MG-ADL) from Baseline

  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 Outcomes (8)

• Time to achievement of minimal manifestations (MMS) or better

  From Baseline to 6 months

• Time to achievement of Patient-Acceptable Symptom States

  From Baseline to 6 months

• Change of Quantitative Myasthenia Gravis (QMG) Scores from Baseline

  Baseline, 1 month, 3 months, 6 months

• Change of Myasthenia Gravis Quantity-of-Life Scale (MG-QoL15) from Baseline

  Baseline, 1 month, 3 months, 6 months

• Changes of MG-ADL subscores from baseline

  Baseline, 1 month, 3 months, 6 months

Study Arms (2)

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

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

Interventions

Pyridostigmine, Prednisone, Tacrolimus DRUG

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.

Also known as: Pyridostigmine Bromide, Deltacortone/Meticorten/Prednisone Acetate Tablets, Prograf/FK506

Combined Immunotherapy

Pyridostigmine, Tacrolimus DRUG

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.

Also known as: Pyridostigmine Bromide, Prograf/FK506

Tacrolimus monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Myasthenia Gravis

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Da, Yuwei, M.D.: lead

Study Sites (1)

Yuwei Da

Beijing, Beijing Municipality, 100053, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples are collected at baseline and 1, 3, 6 months after treatment initiation to monitor side effect and serum IL-2 level.

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Pyridostigmine Bromide; Prednisone; Tacrolimus

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Macrolides; Lactones; Organic Chemicals

Study Officials

• Yuwei Da, M.D.

  Xuanwu Hospital, Beijing

  STUDY CHAIR

Central Study Contacts

Yuwei Da, M.D.

CONTACT

00-86-010-83198493; dayuwei1000@163.com

Yuwei Da, M.D.

CONTACT

00-86-010-83198493; dayuwei100@hotmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Months
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2021
• First Posted: February 24, 2021
• Study Start: January 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: October 31, 2024
• Last Updated: February 24, 2021

Record last verified: 2021-02

Locations

CN (1)