Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis (BETA-MG)

University of Aarhus

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Myasthenia Gravis

Treatments: Drug: Placebo oral capsule; Drug: Salbutamol 4Mg Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT03914638

BETA-MG-01

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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30 participants in 2 patient groups, including a placebo group

Active

Experimental group

Description:

Active intervention arm. Treatment for 8 weeks per treatment period.

Treatment:

Drug: Salbutamol 4Mg Tablet

Placebo

Placebo Comparator group

Description:

Placebo arm. Treatment for 8 weeks per treatment period.

Treatment:

Drug: Placebo oral capsule