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

Sponsor:	Gary Cutter, PhD
Collaborator:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):	Gary Cutter, PhD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:	NCT00294658

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 III

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:

MedlinePlus related topics: Myasthenia Gravis

Drug Information available for: Prednisone

U.S. FDA Resources

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

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

Contacts

Contact: Greg Minisman, MA	(205) 934-4905
Contact: Gary Cutter, PhD	(205) 934-4905

Show 50 Study Locations

Sponsors and Collaborators

Gary Cutter, PhD

National Institute of Neurological Disorders and Stroke (NINDS)

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:	Gary Cutter, PhD, Principle Investigator, 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:	October 18, 2011
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
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 12, 2012