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

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.

Study Overview

• Status: Unknown
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: Salbutamol 4Mg Tablet; Drug: Placebo oral capsule

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).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jan LS Thomsen, MD; Phone Number: 0045 78450000; Email: jathms@rm.dk

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Recruiting
    • Department of Neurology, Aalborg University Hospital
    • Contact: Izabella Obál, PhD
  • Aarhus, Denmark, 8200
    • Recruiting
    • Neurology, Aarhus University Hospital
    • Contact: Jan Thomsen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active; Active intervention arm. Treatment for 8 weeks per treatment period.	Drug: Salbutamol 4Mg Tablet; Salbutamol 4 mg, three times daily
Placebo Comparator: Placebo; Placebo arm. Treatment for 8 weeks per treatment period.	Drug: Placebo oral capsule; Placebo, three times daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Treatment Tolerability	Tolerability assessed by rate of adverse events and drug discontinuation in both treatment periods.	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myasthenia Gravis Activity of Daily Living (MG-ADL)	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Neuro QOL	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Quantitative Myasthenia Gravis (QMG)	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Myasthenia Gravis Composite (MG-Composite)	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).	8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Study Director: Jan LS Thomsen, MD, Department of Clinical Medicine, Aarhus University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): October 31, 2021
• Study Completion (Anticipated): October 31, 2021

Study Registration Dates

• First Submitted: April 11, 2019
• First Submitted That Met QC Criteria: April 11, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): April 6, 2020
• Last Update Submitted That Met QC Criteria: April 2, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: BETA-MG-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No