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
  Purpose

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.


Condition Intervention Phase
Myasthenia Gravis
Procedure: thymectomy
Drug: prednisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center, Single-Blind, Randomized Study Comparing Thymectomy to No Thymectomy in Non-Thymomatous Myasthenia Gravis (MG) Patients Receiving Prednisone

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome 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 ] [ 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 ]

Estimated Enrollment: 150
Study Start Date: June 2006
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Procedure: Extended Transsternal Thymectomy + prednisone
Procedure: thymectomy
The thymectomy will be performed as soon as possible after randomization.
Active Comparator: 2
Drug: prednisone
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 =/> 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00294658

  Hide Study Locations
Locations
United States, Alabama
Data Coordination Center: University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of Southern California, Doheny Institute
Los Angeles, California, United States, 90033
University of California Irvine, 101 The City Drive S, Bldg. 22 C, Route 13
Orange, California, United States, 92868
United States, Florida
University of Florida Jacksonville, Tower I, 8th Floor, 580 W. 8th ST.
Jacksonville, Florida, United States, 32209
University of Miami, 1120 NW 14th Street, Suite 1300
Miami, Florida, United States, 33136
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Indiana
Indiana University, Dept of Neurology, Regenstrief Health Center, 6th floor, 1050 Walnut St, Indiana University Medical Center
Indianapolis, Indiana, United States, 46202-2859
United States, Kansas
The University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Brigham and Women's Hospital, 75 Francis Street, 5th Floor Tower
Boston, Massachusetts, United States, 02115-6110
United States, Michigan
Wayne State University School of Medicine, 4201 St Antoine, 8D UHC
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63103-2097
United States, New Jersey
Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08901
United States, New York
Mt. Sinai School of Medicine
New York, New York, United States, 10029
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western Reserve University, University Hospitals of Cleveland, 1100 Euclid Avenue
Cleveland, Ohio, United States, 44106
The Ohio State University Medical Center, Rm 461 Means Hall, The Ohio State University Medical Center,1654 Upham Dr.
Columbus, Ohio, United States, 43210
United States, Texas
University of Texas Southwestern Medical Center, 5232 Harry Hines Blvd,
Dallas, Texas, United States, 75390-8897
Nerve and Muscle Center of Texas
Houston, Texas, United States, 77030
University of Texas Health Science Center, Mail code 7883, 7703 Floyd Curl Drive
San Antonio, Texas, United States, 78229-3900
United States, Vermont
University of Vermont College of Medicine, Given Bldg C225, 89 Beaumont Avenue
Burlington, Vermont, United States, 05405
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Argentina
Centro de Asistencia Docencia e Investigacion en Miastenia (CADIMI) Av. Forest 1146 - Ciudad Autonoma de Buenos Aires
Buenos Aires, Argentina
Australia
The Royal Melbourne Hospital, Dept of Neurology, Royal Melbourne Hospital
Victoria, Australia, 3050
Brazil
Hospital de Base do Distrito Federal
Brasilia, Brazil, CEP 71640 255
Hospital De Clinicas Da Universidade Federal Do Parana
Curitiba, Brazil, 80060-900
Federal University of Rio de Janeiro
Rio de Janeiro, Brazil, CEP 20520-053
Canada, British Columbia
University of British Columbia
Vancouver, British Columbia, Canada, V6T 2B5
Canada
McGill University Health Center
Montreal, Canada, H3G 1A4
Chile
Hospital Del Salvador, Departamento de Ciencias Neurológicas, Universidad de Chile, Salvador 95 Of 416, Providencia
Santiago, Chile
Germany
Heinrich-Heine-University Dusseldorf
Dusseldorf, Germany, D-40225
Johannes Gutenberg-Universitat, Klinikum der Johannes Gutenberg-Universität, Klinik und Poliklinik für Neurologie, Langenbeckstr
Mainz, Germany, 55101
University of Regensburg, Dept. of Neurology, Universitätsstr. 84, D
Regensburg, Germany, 93043
Universitat Tubingen
Tubingen, Germany, 72076
Italy
Catholic University, Universita Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, e
Rome, Italy
University of Rome
Rome, Italy, 00189
Japan
Kanazawa University, Department of Neurology, Kanazawa University Hospital, 13-1 Takaramachi
Kanazawa, Ishikawa, Japan, 920-8641
Mexico
Instituto Nacional de Ciencias Medicas y Nutricion
Tlalpan, Mexico, 14000
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 RC
Poland
Medical University of Warsaw
Warsaw, Poland, 02 097
South Africa
University of Cape Town, Division of Neurology E8-74, Groote Schuur Hospital,Observatory
Cape Town, South Africa
Taiwan
Shin Kong Wu Ho-Su Memorial Hospital
Taipei City, Taiwan, 111
Thailand
Ramathibodi Hospital Mahidol University
Bangkok, Thailand, 10400
United Kingdom
South Glasgow University Hospitals
Glasgow, United Kingdom, G51 4TF
The Walton Centre for Neurology and Neurosurgery, Lower Lane, Fazakerley
Liverpool, United Kingdom, L9 7LJ
King's College Hospital
London, United Kingdom, SE5 9RS
University of Oxford, Dept of Clinical Neurology, University of Oxford, Radcliffe Infirmary
Oxford, United Kingdom, OX26HE
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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
  More Information

No publications provided

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00294658     History of Changes
Other Study ID Numbers: R01NS050733, 1U01NS042685-01A2, CRC, 2UO1NS042685-06
Study First Received: February 21, 2006
Last Updated: December 10, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Alabama at Birmingham:
myasthenia gravis
thymectomy
prednisone
corticosteroid
extended transsternal thymectomy
ETTX
MG
thymus
thymoma

Additional relevant MeSH terms:
Myasthenia Gravis
Muscle Weakness
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Prednisone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014