Acetylcholine Receptors From Human Muscles as Pharmacological Target for ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— AchALS  

Official title:

Acetylcholine Receptors From Human Muscles as Pharmacological Target for ALS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02645461
• Other study ID #: 3314
• Status: Completed
• Phase: N/A
• First received: December 22, 2015
• Last updated: January 1, 2016
• Start date: January 2014
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Drug:
• endocannabinoid palmitoylethanolamide (PEA)
Endocannabinoid palmitoylethanolamide (PEA) (ultramicronized) 600 mg twice daily
• Riluzole
Riluzole 50 mg twice daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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