Official Title: “A Multi-Center, Single-Blind, Randomized Study Comparing Thymectomy to No Thymectomy in Non-Thymomatous Myasthenia Gravis (MG) Patients Receiving Prednisone”

The purpose of this trial is to determine if thymectomy combined with prednisone therapy is more beneficial in treating non-thymomatous myasthenia gravis than prednisone therapy alone.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment

Study Primary Completion Date: November 2009

Myasthenia gravis (MG) is an autoimmune disease involving the thymus in which 85 percent of patients have antibodies to muscle acetylcholine receptors (AchR-Ab) that interfere with neuromuscular transmission. MG frequently causes severe disability that can be life-threatening. Thymectomy—a surgical procedure that removes thymus gland tissue from the chest cavity—has been an established therapy for non-thymomatous MG, or MG without thymoma, for more than 60 years (based on retrospective, non-randomized studies). Corticosteroids are now being used increasingly either as the sole treatment or in combination with thymectomy.

Both therapies have associated adverse effects and indications for their use based on randomized trial data are lacking.

The purpose of this 5-year trial is to determine if the surgical procedure, extended transsternal thymectomy (ETTX), combined with prednisone therapy is more beneficial in treating individuals with non-thymomatous MG than prednisone therapy alone. More specifically, this study will determine 1) if ETTX combined with prednisone results in a greater improvement in myasthenic weakness, compared to prednisone alone; 2) if ETTX combined with prednisone results in a lower total dose of prednisone, thus decreasing the likelihood of concurrent and long-term toxic effects, compared to prednisone alone; and 3) if ETTX combined with prednisone enhances quality of life by reducing adverse events and symptoms associated with the therapies, compared to prednisone alone.

Learning that thymectomy results in a meaningful reduction of prednisone dosage or even full withdrawal or reduces side effects related to prednisone would support using the two treatments—thymectomy and prednisone—together. However, if no meaningful reduction of prednisone dosage or side effects is shown, the results would mean that using the two treatments together offers no advantages over prednisone treatment alone.

After an initial screening, study participants will be randomized either to undergo the surgical procedure ETTX and receive prednisone treatment, or to receive prednisone treatment alone without surgery. Participants will be followed for at least 3 years.

Intervention(s) in this Clinical Trial

• Procedure: thymectomy
  • The thymectomy will be performed as soon as possible after randomization.
• Drug: prednisone
  • Prednisone regimen will be every other day, starting at 10mg. The dose will increase by 10mg every 2 days to a target dose.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
• Active Comparator: 2

Primary Measures

• Comparison of the prednisone treatment alone to thymectomy (ETTX) plus prednisone treatment, based on the clinical response to therapy measured over the 3 year trial period by the Area Under the Quantitative Myasthenia Gravis Weakness Score
  • Time Frame: 3 years
    Safety Issue?: Yes
• Testing the difference of total prednisone used over the 3 year trial period measured by pill count from blister packs (Area Under the prednisone Dose Time Curve, AUDTC) conditional on the results of comparing AUQMG.
  • Time Frame: 3 years
    Safety Issue?: Yes

Inclusion Criteria:

• Male and female MG patients age 18 to 60 years inclusive
• Onset of generalized MG within the last 3 years
• Positive serum anti-acetylcholine receptor binding antibodies (AchR Ab =/> 1.0 nmol/L)
• MGFA class II-IV at entry, using the MG Foundation of America (MGFA) classification, while receiving optimal anti-cholinesterase treatment with or without oral prednisone

Exclusion Criteria:

• Ocular MG without generalized weakness (MGFA Class I) or minimal weakness that would not require the use of corticosteroids
• Myasthenic weakness requiring intubation (MGFA Class IV) in the prior month
• Immunosuppressive therapy other than corticosteroids in the preceding year
• Medically unfit for thymectomy
• Chest CT evidence of thymoma.
• Pregnancy or lactation; contraindications to the use of corticosteroids, unless postmenopausal or surgically sterile. Women considering becoming pregnant during the period of the study are to be excluded.
• A serious concurrent medical, neurological or psychiatric condition that would interfere with thymectomy or subsequent clinical assessments
• Current alternate day dose of prednisone > than 1.5 mg/kg or 100 mg or the equivalent daily doses (> 0.75 mg/kg or 50 mg).
• Participation in another experimental clinical trial
• History of alcohol or drug abuse within the 2 years prior to randomization.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Alabama at Birmingham

Overall Clinical Trial Officials and Contacts

Gary Cutter, PhD Principal Investigator University of Alabama at Birmingham School of Public Health, Department of Biostatistics  

Overall Contact: Greg Minisman, MA (205) 934-4905 

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00294658

Study ID Number: R01NS050733

ClinicalTrials.gov Identifier: NCT00294658

Health Authority: United States: Federal Government