- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05860244
Effect of Salbutamol on Walking Capacity in Ambulatory ALS Patients (WALKALS)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Based on a strong preclinical and clinical rationale the main hypothesis is that the administration of salbutamol in ALS patients may improve the walking capacity related to motor fatigue by enhancing the neuromuscular transmission. Salbutamol may also exert a neuroprotective effect and slow down the progression of clinical signs and symptoms.
To test these hypotheses, the investigator team will implement a monocentric, randomized, controlled, pilot study to evaluate the effect of salbutamol on walking capacity in ambulatory ALS patients with a total duration of 24 months and a treatment period of 6 months for each patient. The project Team will use as secondary and exploratory endpoints target engagement and efficacy up-to date biomarkers such as quantitative muscle strength evaluation, functional neuromuscular evaluation and spinal and muscle MRI. Tolerability and safety will also be studied. Salbutamol has been used for a long time and is usually well tolerated. The objective of the study is to evidence a signal of efficacy paving the way for a confirmatory phase 3 trial.
In parallel to this, the use of muscle and spinal MRI as well as of quantitative muscle strength evaluation as exploratory endpoints will pave the way to their development as biomarkers of disease progression in ALS. Thanks to the data collected in this study, the team will give proof of their accuracy, with a view to ameliorate the prognostication and monitoring of disease progression and survival, as well as to improve the understanding of the interaction between muscular and central degeneration. A further aim of this study will be to provide a proof of concept that spinal and muscle MRI can constitute a biomarker of the efficacy of investigational drugs targeting muscles.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Giorgia Querin, MD
- Phone Number: +33 01 42 16 58 70
- Email: g.querin@institut-myologie.org
Study Contact Backup
- Name: Pierre-Francois Pradat, MD
- Phone Number: +33 01 42 16 24 71
- Email: pierre-francois.pradat@aphp.fr
Study Locations
-
-
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Paris, France, 75013
- Hopital Pitie Salpetriere
-
Contact:
- Giorgia Querin, MD
- Phone Number: +33 01 42 16 58 70
- Email: g.querin@institut-myologie.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Subjects who meet the revised El Escorial criteria for probable or definite sporadic ALS
- Adult patients between 18 and 75 years of age
- Patients who are ambulatory and able to perform the 6MWT and quantitative muscle testing at screening (ALSFRS-R-walking = 3)
- Patients able and willing to travel to the site, and, in the investigator's opinion, who are likely to attend visits for at least 6 months
- Patients who signed written informed consent
- Stable dose of riluzole for a minimum of 4 weeks prior to baseline or has not taken it for 4 weeks prior to baseline
- For child-bearing aged women, efficient contraception (cf protocol p32)
- Forced vital capacity (fVC) in a sitting position > 70 %
Exclusion Criteria:
- Patients with significant spasticity of the lower limbs interfering with walking capacity (Ashworth scale score > 2)
- Patients with fronto-temporal dementia associated with ALS
- Patients presenting respiratory insufficiency causing dyspnea during walking
- Patients taking drugs that could interfere with NMJ function (anticholinesterase …) or muscle function (steroids, statins…)
- Patients taking any forbidden drugs (see list in annex)
- Hypersensitivity to salbutamol or to excipients of the drug and placebo
- Known contraindication for the studied drug such as ischemic cardiomyopathy or risk of ischemic cardiomyopathy: history of ischemic heart disease or coronaropathy or/and significant ischemic ECG alterations at screening visit
- Any clinically significant alterations in the following biological parameters glycemia, kalemia, creatinemia and hematology in the month prior to inclusion according to local laboratory threshold (cf protocol page 33)
- Vulnerable persons defined in Articles L1121-5 to L 1121-8-1 and L1122-1-2 of the Code de la Santé Publique* (*CSP)
- Participation in another interventional trial up to 3 months before inclusion
- Patients having any relevant concomitant disease considered at risk of interfering with study procedures in the opinion of the investigator
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Salbutamol
Salbutamol 2mg/5ml syrup : 2mg TID salbutamol for 3 months, then 4 mg TID for 3 months For each investigated dose (6 mg then 12 mg), the treatment will be titrated during a 4 days period: At beginning of the first 3-month period : Month 0 D1: 2mg in the morning; D2-D3: 2 mg in the morning and 2mg in the evening for two days; From D4 and until the end of first 3-month period (until the M3 follow-up visit): 2mg in the morning, at noon and in the evening At beginning of the second 3-month period : Month 3 D1: 4mg in the morning, 2mg at noon, 2 mg in the evening; D2: 4 mg in the morning, 2 mg at noon and 4mg in the evening; J4 and for 3 months (until the M6 follow-up visit) : 4mg in the morning, at noon and in the evening. |
Salbutamol for 6 months
|
Placebo Comparator: placebo of salbutamol
Placebo syrup : 2mg TID salbutamol for 3 months, then 4 mg TID for 3 months For each investigated dose (6 mg then 12 mg), the treatment will be titrated during a 4 days period: At beginning of the first 3-month period : Month 0 D1: 2mg in the morning; D2-D3: 2 mg in the morning and 2mg in the evening for two days; From D4 and until the end of first 3-month period (until the M3 follow-up visit): 2mg in the morning, at noon and in the evening At beginning of the second 3-month period : Month 3 D1: 4mg in the morning, 2mg at noon, 2 mg in the evening; D2: 4 mg in the morning, 2 mg at noon and 4mg in the evening; J4 and for 3 months (until the M6 follow-up visit) : 4mg in the morning, at noon and in the evening. |
Placebo Syrup for 6 months
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
walking capacity
Time Frame: Month 6
|
6 minutes walking test distance (6MWT)
|
Month 6
|
walking capacity
Time Frame: Month 3
|
6 minutes walking test distance (6MWT)
|
Month 3
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Target engagement:
Time Frame: baseline, month 3, month 6
|
percentage of change of the decrement at electromyography after repetitive nerve stimulation.
|
baseline, month 3, month 6
|
functional quantitative decline description over time in ALS patients
Time Frame: baseline, month 3, month 6
|
Revised ALS Functional Rating Scale-r (ALSFRS-r) composed by 12 questions scoring from 0 to 4 with a maximal score of 48
|
baseline, month 3, month 6
|
walking scale
Time Frame: baseline, month 3, month 6
|
Twelve items Multiple Sclerosis (MS) Walking Scale (12-MSWS) ( score: 5 to 60 ( severe difficulty)) .
Walking improvement on the MSWS-12 is indicated by negative change scores.
|
baseline, month 3, month 6
|
Fatigue and depression scale
Time Frame: baseline, month 3, month 6
|
Fatigue Severity Scale (FSS) is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders.
( score : 9 (no fatigue ) to 63 (extreme fatigue)
|
baseline, month 3, month 6
|
Respiratory assessment
Time Frame: baseline, month 3, month 6
|
Forced Vital Capacity (FVC): the maximum amount of air that a person can exhale as hard and as long as possible from the lungs after a maximum inspiration and Forced Expiratory Volume in the first second of exhalation (FEV1) : FEV1 is the most frequently used index for assessing airway obstruction, bronchoconstriction or bronchodilation
|
baseline, month 3, month 6
|
Thigh muscle volume
Time Frame: baseline, month 3, month 6
|
bioelectrical impedance analysis (BIA)
|
baseline, month 3, month 6
|
Muscle volume
Time Frame: baseline, month 3, month 6
|
Muscle MRI in cm3
|
baseline, month 3, month 6
|
Biomarkers of muscle damage
Time Frame: baseline, month 3, month 6
|
CPK, LDH and creatinine serum levels
|
baseline, month 3, month 6
|
Quality of life scale
Time Frame: baseline, month 6
|
The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) ( score: 0 to 160 bad quality of life)
|
baseline, month 6
|
Motor unit number
Time Frame: baseline, month 6
|
Motor unit count (MUNIX method)
|
baseline, month 6
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Metabolic Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Spinal Cord Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Sclerosis
- Motor Neuron Disease
- Amyotrophic Lateral Sclerosis
- 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
- APHP190724
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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