Official Title: “Efficacy of Prednisone In the Treatment of Ocular Myasthenia: The EPITOME' Study”

The purpose of this study is to evaluate the efficacy and tolerability of prednisone in patients diagnosed with ocular myasthenia.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2013

The purpose of this study is to learn two things about prednisone in patients with ocular myasthenia. The first thing we aim to learn is whether or not prednisone is effective in improving the symptoms of double vision and drooping eyes that are experienced by patients with ocular myasthenia. The second thing we aim to learn is whether we can find a dose of prednisone that is well tolerated and safe. The overall goal is to find out whether a dose of prednisone that is safe and well tolerated is also effective in improving the symptoms of ocular myasthenia.

After completing screening assessments to confirm eligibility, all participants will receive treatment with pyridostigmine. If a participant's symptoms do not resolve within the first month while being treated with pyridostigmine, they will be randomized to receive prednisone or placebo. The amount of study medication a participant receives will depend on how their symptoms respond to the medication and if they experience any side effects.

After four months, participants that continue to have symptoms of ocular myasthenia and do not have side effects will receive open label high dose prednisone. Participants that no longer have symptoms will taper their dose of study drug in a double-blind fashion.

Intervention(s) in this Clinical Trial

• Drug: Prednisone
  • Prednisone and placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone or matching placebo.
• Drug: Placebo
  • Prednisone and placebo dosages will be adjusted based on combined measures of tolerability and efficacy. Capsules will contain 10mg of prednisone or matching placebo.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Prednisone
  • Corticosteroid
• Placebo Comparator: Placebo
  • Matched, inactive substance

Primary Measures

• The proportion of subjects who 'fail treatment' during the four months of the double blind phase of the study.
  • Time Frame: 4 months
    Safety Issue?: Yes

Secondary Measures

• Time to sustained minimal manifestation status
  • Time Frame: 4 months
    Safety Issue?: No
• Time to an ocular quantitative myasthenia gravis (QMG) score of zero
  • Time Frame: 4 months
    Safety Issue?: No
• Change in quality of life as measured by the NEI-VFQ-25, the 10-item neuro-ophthalmological supplement to the VFQ-25 and the INQoL.
  • Time Frame: 4 months
    Safety Issue?: No
• Occurrence of adverse events
  • Time Frame: 4 months
    Safety Issue?: Yes

Inclusion Criteria:

• Weakness confined to the extra-ocular muscles, eyelid levator and eye closure with an ocular-QMG1 score ≥ 1
• At least one abnormal diagnostic test:
• 1. Positive ice test
• 2. Elevated acetylcholine receptor antibody titers
• 3. Positive Tensilon test, 4. Abnormal repetitive nerve stimulation (> 10% decrement following slow repetitive nerve stimulation) of any nerve-muscle pair, or 5. Abnormal jitter on single fiber or concentric needle electromyography in any muscle
• Brain MRI that demonstrates no central nervous system pathology that mimics ocular myasthenia. Brain MRI is required only if acetylcholine receptor antibodies are negative or there is no electrophysiological confirmation, i.e. MRI is required if the evidence supporting the clinical diagnosis of OM rests solely on a positive ice test or a positive tensilon test.
• Either no prior treatment or an inadequate trial of pyridostigmine (where inadequate is defined as a trial in which the dosage was titrated to neither efficacy [MMS] nor adverse events that did not resolve with the addition of a selective muscarinic antagonist)
• Age 18 years or older, male or female
• Capable of providing informed consent and complying with study procedures
• Identifiable primary care physician to assist with management of medical complications that may arise as a consequence of steroid therapy

Exclusion Criteria:

• Disease duration (time since symptom onset) > 2 years
• Treatment with prednisone or other corticosteroids within 90 days of randomization
• Treatment with azathioprine, cyclosporine, mycophenolate mofetil or other immune suppressive medication since onset of MG unless dosages of these medications and/or duration of therapy with these medications are clinically insignificant in the judgment of the PI.
• Intravenous immunoglobulin or plasma exchange within 90 days of randomization
• Prior thymectomy or history of thymoma
• Contraindication to steroids (poorly controlled diabetes, glaucoma or hypertension, history of prior steroid intolerance, obesity [BMI > 30kg/m2] or a history of osteoporotic fracture)
• Unwillingness to be randomized to a trial of prednisone or placebo if symptoms respond inadequately to pyridostigmine
• Pregnant or lactating
• Renal failure, active thyroid or hepatocellular disease, chronic infection, poorly controlled cardiac disease, unstable psychiatric illness, untreated major depression or any other illness that would, in the opinion of the treating neurologist, make it unsafe for the patient to participate in the trial.
• Receipt of another investigational drug within 30 days of Randomization

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Emory University

Overall Clinical Trial Officials and Contacts

Michael Benatar, MBChB, DPhil Principal Investigator Emory University  

Overall Contact: Michael Benatar, MBChB, DPhil  michael.benatar@emory.edu

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00995722

Study ID Number: FD-R-03710-01

ClinicalTrials.gov Identifier: NCT00995722

Health Authority: United States: Food and Drug Administration