Amyotrophic Lateral Sclerosis
Conditions
Brief 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.
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.
Interventions
DRUGendocannabinoid palmitoylethanolamide (PEA)
Endocannabinoid palmitoylethanolamide (PEA) (ultramicronized) 600 mg twice daily
DRUGRiluzole
Riluzole 50 mg twice daily
Sponsors
University of Roma La Sapienza
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in pulmonary capacity of ALS patients at 6 months. | six months | Changes of the percentage of predicted forced vital capacity (FVC %) will be measured |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in acetylcholine receptors (AChR) currents and Analysis of the composition of AChRs subunits in ALS muscles. | six months | Utilization of voltage-clamp intracellular recordings in oocytes transplanted with membranes from ALS muscles. |
| Changes from baseline in muscle strength of ALS patients at 6 months. | six months | Changes of the Medical Research Council (MRC) scale score will be measured |
| Changes from baseline in electrophysiological parameters of ALS patients at 6 months | six months | Changes of the compound muscle action potential (CMAP) amplitude of ulnar and phrenic nerves will be measured |
Outcome results
None listed