Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00294658
First received: February 21, 2006
Last updated: December 10, 2013
Last verified: December 2013

February 21, 2006
December 10, 2013
June 2006
August 2015   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as 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 ] [ Designated as safety issue: Yes ]
  • 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
  • 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.
Complete list of historical versions of study NCT00294658 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy
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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Myasthenia Gravis
  • 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.
  • Active Comparator: 1
    Procedure: Extended Transsternal Thymectomy + prednisone
    Intervention: Procedure: thymectomy
  • Active Comparator: 2
    Drug: prednisone
    Intervention: Drug: prednisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
150
August 2015
August 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Male and female MG patients age greater than 18 and less than 65 years
  • Onset of generalized MG within the last 5 years
  • Positive serum anti-acetylcholine receptor binding antibodies (AchR Ab =/> 1.00 nmol/L. AchRAb levels of 0.50-0.99 nmol/L will be acceptable if there is another confirmatory test for MG, including single-fiber EMG, repetitive nerve stimulation, or unequivocal edrophonium testing.)
  • 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.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Brazil,   Canada,   Chile,   Germany,   Italy,   Japan,   Mexico,   Netherlands,   Poland,   South Africa,   Taiwan,   Thailand,   United Kingdom
 
NCT00294658
R01NS050733, 1U01NS042685-01A2, CRC, 2UO1NS042685-06
Yes
University of Alabama at Birmingham
University of Alabama at Birmingham
National Institute of Neurological Disorders and Stroke (NINDS)
Principal Investigator: Gary Cutter, PhD University of Alabama at Birmingham School of Public Health, Department of Biostatistics
Principal Investigator: Gil Wolfe, MD University of Texas Southwestern Medical Center
University of Alabama at Birmingham
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP