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

Myasthenia Gravis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00294658
• Other study ID #: R01NS050733
• Secondary ID: 1U01NS042685-01A
• Status: Active, not recruiting
• Phase: Phase 3
• First received: February 21, 2006
• Last updated: April 13, 2016
• Start date: June 2006
• Est. completion date: July 2016

Study information

• Verified date: April 2016
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 126
• Est. completion date: July 2016
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myasthenia Gravis

Intervention

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.

Locations

Country	Name	City	State
Argentina	Centro de Asistencia Docencia e Investigacion en Miastenia (CADIMI) Av. Forest 1146 - Ciudad Autonoma de Buenos Aires	Buenos Aires
Australia	The Royal Melbourne Hospital, Dept of Neurology, Royal Melbourne Hospital	Victoria
Brazil	Hospital de Base do Distrito Federal	Brasilia
Brazil	Hospital De Clinicas Da Universidade Federal Do Parana	Curitiba
Brazil	Federal University of Rio de Janeiro	Rio de Janeiro
Canada	McGill University Health Center	Montreal
Canada	University of British Columbia	Vancouver	British Columbia
Chile	Hospital Del Salvador, Departamento de Ciencias Neurológicas, Universidad de Chile, Salvador 95 Of 416, Providencia	Santiago
Germany	Heinrich-Heine-University Dusseldorf	Dusseldorf
Germany	Johannes Gutenberg-Universitat, Klinikum der Johannes Gutenberg-Universität, Klinik und Poliklinik für Neurologie, Langenbeckstr	Mainz
Germany	University of Regensburg, Dept. of Neurology, Universitätsstr. 84, D	Regensburg
Germany	Universitat Tubingen	Tubingen
Italy	Catholic University, Universita Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, e	Rome
Italy	University of Rome	Rome
Japan	Kanazawa University, Department of Neurology, Kanazawa University Hospital, 13-1 Takaramachi	Kanazawa	Ishikawa
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion	Tlalpan
Netherlands	Leiden University Medical Center	Leiden
Poland	Medical University of Warsaw	Warsaw
South Africa	University of Cape Town, Division of Neurology E8-74, Groote Schuur Hospital,Observatory	Cape Town
Taiwan	Shin Kong Wu Ho-Su Memorial Hospital	Taipei City
Thailand	Ramathibodi Hospital Mahidol University	Bangkok
United Kingdom	South Glasgow University Hospitals	Glasgow
United Kingdom	The Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley	Liverpool
United Kingdom	King's College Hospital	London
United Kingdom	University of Oxford, Dept of Clinical Neurology, University of Oxford, Radcliffe Infirmary	Oxford
United States	Medical College of Georgia	Augusta	Georgia
United States	Data Coordination Center: University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham and Women's Hospital, 75 Francis Street, 5th Floor Tower	Boston	Massachusetts
United States	University of Vermont College of Medicine, Given Bldg C225, 89 Beaumont Avenue	Burlington	Vermont
United States	University of Virginia	Charlottesville	Virginia
United States	Case Western Reserve University, University Hospitals of Cleveland, 1100 Euclid Avenue	Cleveland	Ohio
United States	The Ohio State University Medical Center, Rm 461 Means Hall, The Ohio State University Medical Center,1654 Upham Dr.	Columbus	Ohio
United States	University of Texas Southwestern Medical Center, 5232 Harry Hines Blvd,	Dallas	Texas
United States	Wayne State University School of Medicine, 4201 St Antoine, 8D UHC	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Nerve and Muscle Center of Texas	Houston	Texas
United States	Indiana University, Dept of Neurology, Regenstrief Health Center, 6th floor, 1050 Walnut St, Indiana University Medical Center	Indianapolis	Indiana
United States	University of Florida Jacksonville, Tower I, 8th Floor, 580 W. 8th ST.	Jacksonville	Florida
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	University of Southern California, Doheny Institute	Los Angeles	California
United States	University of Miami, 1120 NW 14th Street, Suite 1300	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Mt. Sinai School of Medicine	New York	New York
United States	University of California Irvine, 101 The City Drive S, Bldg. 22 C, Route 13	Orange	California
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	University of Texas Health Science Center, Mail code 7883, 7703 Floyd Curl Drive	San Antonio	Texas
United States	University of Washington	Seattle	Washington
United States	St. Louis University	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  Germany,  Italy,  Japan,  Mexico,  Netherlands,  Poland,  South Africa,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		3 years	Yes
Primary	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.		3 years	Yes