Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis

University of Aarhus30 enrolled

Overview

This study examines the effect of adjuvant therapy with the oral beta-agonist Salbutamol in patients with generalized myasthenia gravis on stable standard of care having residual symptoms.

Myasthenia Gravis (MG) causes various degrees of increased muscular fatigue and ocular, bulbar, respiratory and extremity symptoms. Residual symptoms often remain despite treatment with acetylcholinesterase inhibitors and immunosuppressive agents. Escalation of immunosuppressive treatment may provide additional benefit but is associated with potentially severe side effects, and high economic costs. Treatment with beta-agonists has been investigated in animal models of MG, and in small, randomized pilot studies of generalized MG. Adjuvant therapy with oral beta-agonists in MG may be safe and cheap and may improve symptoms. The trial will examine the tolerability and efficacy of adjuvant therapy with the oral beta-agonist Salbutamol in patients with generalized myasthenia gravis on stable standard of care having residual symptoms. Present study is an investigator-initiated, randomized, placebo-controlled, rater and subject-blinded crossover study. Study consists of Screening Period (4 weeks), Treatment Period 1 (8 weeks), Washout Period (4 weeks), Treatment Period 2 (8 weeks).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Myasthenia Gravis

Interventions

Salbutamol 4Mg TabletDRUG

Salbutamol 4 mg, three times daily

Placebo oral capsuleDRUG

Placebo, three times daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Generalized myasthenia gravis (MGFA IIa-IVb) at screening, verified by ≥ 1 of the following: 1) AchR-antibodies in medical history, 2) Abnormal decrement on repetitive nerve stimulation in medical history * Disease duration of ≥ 1 year * Stable dose of antimyasthenic medications at screening * Residual symptoms with a MG-QOL15 score of ≥ 10 * Age ≥ 18 years * Ability to understand the requirements of the trial and provide written, informed consent Exclusion Criteria: * Evidence of malignancy ≤ 3 years prior to screening, unless deemed completely cured * Thymectomy ≤ 6 months prior to screening * Impending MG crisis or respiratory insufficiency * Worsening of MG symptoms due to other diseases or medications (e.g. infection, beta-blockers, aminoglycosides, etc.) * Other factor(s) or medical condition(s) that may explain residual symptoms * Pregnancy or breast-feeding * Treatment with beta-agonists * Uncontrolled diabetes * Ischemic Heart Disease, Cardiac Arrhythmia or Heart Failure (including hypertrophic cardiomyopathy) * Uncontrolled Hypertension (≥ 160/110) * Known hypersensitivity to any of the study drug components * Treatment with tricyclic antidepressants, monoamineoxidase inhibitors, digoxine, or methylxanthines.

Locations (2)

Department of Neurology, Aalborg University Hospital

Aalborg, Denmark

RECRUITING

Neurology, Aarhus University Hospital

Aarhus, Denmark

RECRUITING

Outcomes

Primary Outcomes

Myasthenia Gravis Quality of Life 15-items (MG-QOL15)

Validated patient reported outcome-questionnaire consisting of 15 items and their impact on quality of life. Results are reported as change from baseline to 8 weeks of treatment in both treatment periods (Visit 4 compared to Visit 2, and Visit 7 compared to Visit 5).