myasthenia gravis MedDRA version: 17.0 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Hidrocloruro de efedrina
(In English: Ephedrine HCl)
Pharmaceutical Form: Tablet
INN or Proposed INN: EPHEDRINE HYDROCHLORIDE
CAS Number: 50-98-6
Other descriptive name: EPHEDRINE HYDROCH
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult patient with a diagnosis of generalised MG based on a) Clinical signs or symptoms suggestive of generalised myasthenia gravis (for example, slowly progressive fluctuating muscle weakness in specific muscle groups); and b) A positive serologic test for acetylcholine receptor (AChR) antibodies 2. Treatment with pyridostigmine, and / or low dose (max. 15 mg/day) prednisone and / or other immunosuppressive drugs does not (or no longer) adequately improve myasthenic symptoms. The dosage of pyridostigmine, prednisone and other immunosuppressive drugs need to have been stable for at least 6 weeks prior to the trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1. Purely ocular myasthenia (i.e. myasthenic symptoms that are limited to the extraocular muscles, such as ptosis and diplopia) 2. Treatment with ephedrine is contraindicated or was not tolerated in the past. Contraindications include myocardial ischemia (angina pectoris and / or myocardial infarction), any cardiac arrhythmia, angle-closure glaucoma, current treatment by a psychologist or psychiatrist, current hypertension (defined as 2 measurements = 140 / 90 mm Hg), poorly regulated diabetes mellitus, inherited QT syndrome or a prolonged QT interval (as indicated by ECG), prostatic hypertrophy and thyrotoxicosis. Patients with relevant drug interactions (MAO inhibitors, alpha and beta blockers) are also excluded. 3. Reliance upon medium-high dose prednisone (> 15 mg/day) and recent (< 3 months) or regular intravenous immunoglobulin (ivIG) or plasma exchange therapy. This excludes steroid-sparing therapy such as azathioprine and excludes supportive therapy such as any form of physical therapy. These treatments are not exclusion criteria for the open label extension phase. 4. Myasthenic crisis in the past 3 months 5. Thymectomy in the past 6 months, or thymectomy (expected) to take place during the trial 6. The patient is unable to fill out the study questionnaires or be interviewed in Dutch, or is unable to undergo the tests needed for the study, or is unable to give informed consent for participation in the study. 7. The investigator can exclude patients for this trial which are deemed not suitable for any reason.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effect of ephedrine on muscle strength/endurance as measured by the QMG for all patients with AChR MG enrolled in this study when ephedrine is added to regular treatment with pyridostigmine and / or a stable low-dose prednisone and / or a stable dose of immunosuppressive treatment.;Primary end point(s): The efficacy of add-on ephedrine for all patients enrolled. This will be done based on an individual’s results on the multiple Quantitative Myasthenia Gravis (QMG, Tindall 1993) measurements taken during the double-blind, multiple crossover phase of the trial.;Secondary Objective: a) To determine the effect of add-on therapy with ephedrine to regular treatment with pyridostigmine and / or low-dose prednisone for individual patients enrolled in this study. b) To determine the feasibility of a larger series of n-of-one trials to investigate the effect of add-on therapy in patients with myasthenia gravis. The feasibility of a larger series of n-of-one trials under the current protocol will be based on the number of completed cycles in this series of n-of-one trials. c) To determine the number of people who are initially eligible for the study, the number of people who enrol in and complete the multiple crossover phase and the number of people who subsequently proceed to the open label extension phase. d) To explore patients’, physicians’ and pharmacists’ perspectives on the use of series of n-of-one trials; e) To record any adverse events of ephedrine when added to the existing treatment of the MG patient.;Timepoint(s) of evaluation of this end point: Six weeks after inclusion (per patient, analysis after inclusion of all patients) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) The effect of add-on ephedrine as measured by QMG for individual patients enrolled in this study. b) The feasibility of a larger series of n-of-one trials. We will conclude that a larger series of n-of-one trials is feasible under the current protocol if, on average, every patient in this pilot study completes two cycles of the multiple crossover phase. c) Changes in secondary outcome parameters: MG Composite, MG ADL questionnaire. Subjective outcome measures include treatment preference and VAS score of muscle strength in a muscle group chosen by the patient. d) After the cross-over part of the trial, patients who decide to continue ephedrine add-on treatment will be asked to participate in the open label extension study. We will study the long-term effect of ephedrine and compare outcome parameters with baseline and short-term effect. e) The experiences of patients with n-of-one trials by means of semistructured interviews (by telephone) and to evaluate participating professionals’ (physicians’, pharmacists’ and statisticians’) experiences. f) Adverse events of ephedrine treatment as measured by ECG, laboratory tests (haematology, liver and renal function tests) and a questionnaire specifically developed for this purpose.;Timepoint(s) of evaluation of this end point: a) After completion of the multiple cross-over phase (6 weeks after inclusion) b) After completion of the trial c) After completion of the multiple cross-over phase (6 weeks after inclusion) d) After completion of the open label extension phase (duration 6 months, this will be 8 months after initial inclusion in the trial) e) After completion of the trial f) During the entire trial (initially double-blind) | — |
Countries
Netherlands
Contacts
Public ContactEphedrine study contact
Leiden University Medical Center
Outcome results
None listed