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

Condition(s) targeted: Myasthenia Gravis

Intervention: thymectomy (Procedure); prednisone (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Alabama at Birmingham

Official(s) and/or principal investigator(s):
Gary Cutter, PhD, Principal Investigator, Affiliation: University of Alabama at Birmingham School of Public Health, Department of Biostatistics
Gil Wolfe, MD, Principal Investigator, Affiliation: University of Texas Southwestern Medical Center

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

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.

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

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

Primary outcome:

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.

Detailed 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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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 =/> 0. 5

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.

Greg Minisman, MA, Phone: (205) 934-4905

Myasthenia Gravis Foundation of Argentina, FINOCHIETTO 863 Zip:C1143ABH . Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina; Recruiting
Claudio Mazia, Phone: 54 11 4962 6189

The Royal Melbourne Hospital, Dept of Neurology, Royal Melbourne Hospital, Victoria 3050, Australia; Recruiting
John King, Phone: 61 393 482 500

Royal Prince Alfred Hospital and The University of Sydney, Sydney NSW 2006, Australia; Suspended

Hospital De Clinicas Da Universidade Federal Do Parana, Curitiba 80060-900, Brazil; Recruiting
Lineu Werneck, Phone: 55 41 233 3092

Hospital de Base do Distrito Federal, Brasilia CEP 71640 255, Brazil; Recruiting
Elza Tosta, Phone: 55 61 364 1328

Federal University of Rio de Janeiro, Rio de Janeiro CEP 20520-053, Brazil; Recruiting
Marcia Cruz, Phone: 55 21 2568 3939

McGill University Health Center, Montreal H3G 1A4, Canada; Recruiting
Colin Chalk, Phone: 514-934-8059

Hospital Del Salvador, Departamento de Ciencias Neurológicas, Universidad de Chile, Salvador 95 Of 416, Providencia, Santiago, Chile; Recruiting
Gabriel Cea, Phone: 56 2 340 4322

University of Regensburg, Dept. of Neurology, Universitätsstr. 84, D, Regensburg 93043, Germany; Recruiting
Berthold Schalke, Phone: 49 941 941 8042

Johannes Gutenberg-Universitat, Klinikum der Johannes Gutenberg-Universität, Klinik und Poliklinik für Neurologie, Langenbeckstr, Mainz 55101, Germany; Recruiting
Wilfred Nix, Phone: 49 613 117 2224

Universitat Tubingen, Tubingen 72076, Germany; Recruiting
Arthur Melms, Phone: 49-7071-298-0421

Heinrich-Heine-University Dusseldorf, Dusseldorf D-40225, Germany; Recruiting
Sebastian Jander, Phone: 49 211 81 18978

Catholic University, Universita Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, e, Rome, Italy; Recruiting
Amelia Evoli, Phone: 39 06 3015 4435

National Neurological Institute, Milan 20133, Italy; Recruiting
Renato Mantegazza, Phone: 39-022-3942372

University of Rome, Rome 00189, Italy; Recruiting
Giovanni Antonini, Phone: 39 06 80345377

Nagaski University, Nagasaki 852-8501, Japan; Recruiting
Masa Motomura

Instituto Nacional de Ciencias Medicas y Nutricion, Tlalpan 14000, Mexico; Recruiting
Guillermo Garcia Ramos, Phone: 52 55 54 87 09 00, Ext: 2523

Leiden University Medical Center, Leiden 2300 RC, Netherlands; Recruiting
Jan Verschuuren, Phone: 31 71 526 2097

Medical University of Warsaw, Warsaw 02 097, Poland; Recruiting
Hubert Kwiecinski

Hospital Geral de San Antonio, Porto 4099-001, Portugal; Recruiting
Ana Silva, Phone: 35 193 627 3847

University of Cape Town, Division of Neurology E8-74, Groote Schuur Hospital,Observatory, Cape Town, South Africa; Recruiting
Jeannine Heckmann

Hospital Santa Creu I Sant Pau, Neurology Department, Hospital Sta Creu i Sant Pau, C/Mas Casanovas no 90 4o pis 4o modul., Barcelona 08025, Spain; Recruiting
Isabel Illa, Phone: 34 93 556 5986

Shin Kong Wu Ho-Su Memorial Hospital, Taipei City 111, Taiwan; Recruiting
Jiann-Horng Yeh, Phone: 886 2 2838 9437

Ramathibodi Hospital Mahidol University, Bangkok 10400, Thailand; Recruiting
Rawiphan Witoonpanich, Phone: 66 81 4454755

The Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley, Liverpool L9 7LJ, United Kingdom; Recruiting
Bryan Lecky, Phone: 44 151 529 5762

University of Oxford, Dept of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Oxford OX26HE, United Kingdom; Recruiting
Camilla Buckley, Phone: 44-1865-231865

South Glasgow University Hospitals, Glasgow G51 4TF, United Kingdom; Suspended

Salford Royal Hospitals, Salford M6 8HD, United Kingdom; Recruiting
Jon Sussman, Phone: 44 161 206 4591

King's College Hospital, London SE5 9RS, United Kingdom; Not yet recruiting
Fiona Norwood, Phone: 0793 1731390

Data Coordination Center: University of Alabama at Birmingham, Birmingham, Alabama 35294, United States; Not yet recruiting
Greg Minisman, MA, Phone: 205-934-4905
Gary Cutter, PhD, Phone: (205) 934-4905

University of Alabama, Birmingham, Alabama 35294, United States; Recruiting
Shin Oh, Phone: 205-934-2120

University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada; Recruiting
Joel Oger, Phone: 1-604-822-7696

University of California Irvine, 101 The City Drive S, Bldg. 22 C, Route 13, Orange, California 92868, United States; Recruiting
Tahseen Mozaffar, Phone: 714-456-5214

University of Southern California, Doheny Institute, Los Angeles, California 90033, United States; Recruiting
Said Beydoun

University of California Davis, Sacramento, California 95817, United States; Suspended

University of Florida Jacksonville, Tower I, 8th Floor, 580 W. 8th ST., Jacksonville, Florida 32209, United States; Recruiting
Mike Pulley, Phone: 904-244-9922

Emory University, Neurology Department 1365 Clifton Road NE Clinic A, Rm A3432, Atlanta, Georgia 30322, United States; Recruiting
Michael Benatar, Phone: 404-727-3507

Medical College of Georgia, Augusta, Georgia 30912, United States; Not yet recruiting
Michael Rivner, Phone: 706-721-2681

Indiana University, Dept of Neurology, Regenstrief Health Center, 6th floor, 1050 Walnut St, Indiana University Medical Center, Indianapolis, Indiana 46202-2859, United States; Recruiting
Bob Pascuzzi

Kanazawa University, Department of Neurology, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan; Recruiting
Hiroaki Yoshikawa, Phone: +81-76-265-2292

The University of Kansas Medical Center, Kansas City, Kansas 66160, United States; Recruiting
Rick Barohn

Brigham and Women's Hospital, 75 Francis Street, 5th Floor Tower, Boston, Massachusetts 02115-6110, United States; Recruiting
Anthony Amato, Phone: 617-732-5436

Wayne State University School of Medicine, 4201 St Antoine, 8D UHC, Detroit, Michigan 48201, United States; Recruiting
Rich Lewis, Phone: 313-577-1244

Mayo Clinic Rochester, Rochester, Minnesota 55905, United States; Recruiting
Brian Crum, Phone: 507-538-1038

St. Louis University, St. Louis, Missouri 63103-2097, United States; Recruiting
Kaminski Henry, Phone: 314-577-8026

Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, United States; Recruiting
Jerry Belsh, Phone: 732-235-7340

Mt. Sinai School of Medicine, New York, New York 10029, United States; Recruiting
Mark Sivak, Phone: 212-241-8747

University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Emma Ciafaloni

Columbia University, New York, New York 10032, United States; Not yet recruiting
Louis Weimer, Phone: 212-305-1516

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Janice Massey, Phone: 919-660-3853

Case Western Reserve University, University Hospitals of Cleveland, 1100 Euclid Avenue, Cleveland, Ohio 44106, United States; Recruiting
Bashar Katirji, Phone: 216-844-4854

The Ohio State University Medical Center, Rm 461 Means Hall, The Ohio State University Medical Center,1654 Upham Dr., Columbus, Ohio 43210, United States; Recruiting
John Kissel, Phone: 614-293-4981

University of Western Ontario, London Health Sciences Centre, University Hospital, c/o Ms. Sue Robinson Rm c7-110, 339 Windermere Rd., London, Ontario N6A 5A5, Canada; Recruiting
Mike Nicolle, Phone: 519-663-3236

The Ottawa Hospital, Ottawa, Ontario K1H 8L6, Canada; Recruiting
Beth Pringle, Phone: 1 613 737 8689

Sheffield Teaching Hospitals, Sheffield, South Yorkshire S10 2JF, United Kingdom; Suspended

University of Texas Southwestern Medical Center, 5232 Harry Hines Blvd,, Dallas, Texas 75390-8897, United States; Recruiting
Gil Wolfe, Phone: 214-648-9518

University of Texas Health Science Center, Mail code 7883, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, United States; Recruiting
Carlayne Jackson, Phone: 210-567-1945

Nerve and Muscle Center of Texas, Houston, Texas 77030, United States; Recruiting
Aziz Shaibani, Phone: 713-795-0033

University of Torino Medical School, Orbassano, Torino I-10043, Italy; Recruiting
Luca Durelli, Phone: 39 011 902 6245

University of Vermont College of Medicine, Given Bldg C225, 89 Beaumont Avenue, Burlington, Vermont 05405, United States; Recruiting
Rup Tandan, Phone: 802-656-5175

University of Virginia, Charlottesville, Virginia 22908, United States; Recruiting
Larry Phillips

University of Washington, Seattle, Washington 98195, United States; Recruiting
Jane Distad, Phone: 206-543-2340

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States; Recruiting
Alexandru Barboi, Phone: 414-805-5246

Starting date: June 2006
Ending date: August 2010
Last updated: September 21, 2009