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

Phase 2

• Conditions: Myasthenia Gravis
• Interventions: Drug: Salbutamol 4Mg Tablet; Drug: Placebo oral capsule

• Registration Number: NCT03914638
• Lead Sponsor: University of Aarhus

Brief Summary

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.

Detailed 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).

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2019-04-01
• Study First Submitted: 2019-04-11
• Study First Submitted QC: 2019-04-11
• Study First Posted: 2019-04-16
• Status Verified: 2020-04
• Last Update Submitted: 2020-04-02
• Last Update Posted: 2020-04-06
• Primary Completion: 2021-10-31
• Study Completion: 2021-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active	Salbutamol 4Mg Tablet	Active intervention arm. Treatment for 8 weeks per treatment period.
Placebo	Placebo oral capsule	Placebo arm. Treatment for 8 weeks per treatment period.

Primary Outcome Measures

Name	Time	Method
Myasthenia Gravis Quality of Life 15-items (MG-QOL15)	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)	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).
Treatment Tolerability	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)	Tolerability assessed by rate of adverse events and drug discontinuation in both treatment periods.

Secondary Outcome Measures

Name	Time	Method
Myasthenia Gravis Composite (MG-Composite)	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)	Validated scale consisting of 10 items with different weighting assessing severity of symptoms in MG. 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).
Myasthenia Gravis Activity of Daily Living (MG-ADL)	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)	Validated patient-reported outcome scale consisting of 8 disease-related items and their impact on activity of daily living. 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).
Quantitative Myasthenia Gravis (QMG)	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)	Validated rating scale consisting of 13 items measuring muscle function and endurance. 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).
Neuro QOL	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)	Patient reported fatigue-questionnaire used to rate fatigue and 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).

Trial Locations

Locations (2)

Department of Neurology, Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Neurology, Aarhus University Hospital; 🇩🇰 Aarhus, Denmark