Clinical trial NCT03914638: Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis
Official title: Beta-agonist Efficacy and Tolerability as Adjuvant Therapy in Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Myasthenia Gravis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2019-04-16
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Myasthenia Gravis Quality of Life 15-items (MG-QOL15)
timeFrame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
measure: Treatment Tolerability
timeFrame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Secondary outcomes:
measure: Myasthenia Gravis Activity of Daily Living (MG-ADL)
timeFrame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
measure: Neuro QOL
timeFrame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
measure: Quantitative Myasthenia Gravis (QMG)
timeFrame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
measure: Myasthenia Gravis Composite (MG-Composite)
timeFrame: 8 weeks (Treatment Period 1), 8 weeks (Treatment Period 2)
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of Neurology, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Neurology, Aarhus University Hospital
Study officials:
affiliation: University of Aarhus
name: Jan LS Thomsen, MD
role: STUDY_DIRECTOR
References: