Acetylcholine Receptors From Human Muscles as Pharmacological Target for ALS (AchALS)

Amyotrophic lateral sclerosis (ALS) is a fatal disease leading to motor neuron degeneration and progressive paralysis. Other studies have revealed defects in skeletal muscle even in absence of motor neuron anomalies, focusing on acetylcholine receptors (AChRs) and supporting the so-called "dying-back" hypothesis. Outcome of this study will be to understand if the endocannabinoid palmitoylethanolamide (PEA) can reduce the rundown of AChRs currents in ALS muscle, and if it can modify ALS patients' clinical and electrophysiological parameters.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Riluzole; Drug: endocannabinoid palmitoylethanolamide (PEA)

Detailed Description

Outcome:

Monitoring the efficacy and safety of PEA in the treatment of patients with ALS. Analysis of AChR currents and description of the composition of AChRs subunits in ALS muscles

Design of the Study:

A randomized controlled blinded study. Patients with sporadic ALS will receive riluzole alone or riluzole+PEA in order to investigate the clinical and electrophysiological effects of treatment. The expected number of enrolled patients will be 50.

All patients satisfying the selection criteria will be randomized into two groups: a first group will be treated only with riluzole, the second group with riluzole associated with PEA (Normast 600 mg microgranular, 2 sachets/day). The randomization will be done stratifying patietns according to type of clinical onset (bulbar vs. spinal). The patients will be enrolled in the Department of Neurology and Psychiatry, University of Rome "Sapienza".

The visits will be performed at 0 (randomization), 3 and 6 months. At each visit the ALS Functional Rating Scale-Revised (ALSFRS-R), the percentage of predicted forced vital capacity (FVC%), the Medical Research Council (MRC) score for muscle strength limited to the right upper limbs, and the compound muscle action potentials (CMAP) from right ulnar and phrenic nerves will be assessed. A muscle biopsy will be done at the end of the study. The obtained results will be compared with those observed in muscle samples from denervated (non-ALS) control patients.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

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:

• Diagnosis of ALS according to the El-Escorial criteria;
• Age> 18 years;
• ALS Functional Rating Scale-Revised (ALSFRS- r) score> 20;
• Forced Vital Capacity (FVC)> 30%;
• Treatment with Riluzole.

Exclusion Criteria:

• Other diseases motor neurons;
• Experimental treatments in the previous three months;
• Pregnant or breast-feeding;
• Contraindications to the use of riluzole;
• Patients undergoing tracheostomy, enteral or parenteral supply;
• Severe psychiatric disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Riluzole; Riluzole 50 mg twice daily in ALS patients	Drug: Riluzole; Riluzole 50 mg twice daily
Experimental: PEA plus Riluzole; Riluzole 50 mg twice daily plus Endocannabinoid palmitoylethanolamide (PEA) (ultramicronized) 600 mg twice daily in ALS patients	Drug: Riluzole; Riluzole 50 mg twice daily; Drug: endocannabinoid palmitoylethanolamide (PEA); Endocannabinoid palmitoylethanolamide (PEA) (ultramicronized) 600 mg twice daily; Other Names: PEA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in pulmonary capacity of ALS patients at 6 months.	Changes of the percentage of predicted forced vital capacity (FVC %) will be measured	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in acetylcholine receptors (AChR) currents and Analysis of the composition of AChRs subunits in ALS muscles.	Utilization of voltage-clamp intracellular recordings in oocytes transplanted with membranes from ALS muscles.	six months
Changes from baseline in muscle strength of ALS patients at 6 months.	Changes of the Medical Research Council (MRC) scale score will be measured	six months
Changes from baseline in electrophysiological parameters of ALS patients at 6 months	Changes of the compound muscle action potential (CMAP) amplitude of ulnar and phrenic nerves will be measured	six months

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 22, 2015
• First Submitted That Met QC Criteria: December 30, 2015
• First Posted (Estimate): January 1, 2016

Study Record Updates

• Last Update Posted (Estimate): January 5, 2016
• Last Update Submitted That Met QC Criteria: January 1, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Anticonvulsants; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Riluzole; Palmidrol
• Other Study ID Numbers: 3314