Amyotrophic Lateral Sclerosis
Conditions
Keywords
Amyotrophic Lateral Sclerosis, ALS, Growth Hormone, IGF-I
Brief summary
Several drugs have been proposed for ALS. These drugs included: Topiramate, Lamotrigine, creatine, Vit. E, Pentoxifylline, etc. Although most of the trials showed a positive trend, none of them reached a statistically significant result. The only exception is the Riluzole trial, that demonstrated a small but significant reduction in mortality between treated and untreated patients. Aim of our study is to determine if the add-on of GH to treatment with Riluzole is able to reduce neuronal loss in the motor cortex of ALS patients.
Detailed description
Several drugs have been proposed for ALS. These drugs included: Topiramate, Lamotrigine, creatine, Vit. E, Pentoxifylline. Although most of the trials showed a positive trend, none of them reached a statistically significant result. The only exception is the Riluzole trial, that demonstrated a small but significant reduction in mortality between treated and untreated patients. When administered to SOD-1 transgenic mice, IGF-I prolongs survival, ameliorates muscular strength, and reduces weight and motor neuron loss, astrocyte gliosis, and ubiquitin positive protein inclusions. Two clinical trials have been performed in ALS patients with s.c. administration of IGF-I indicating a possible beneficial effect, and a third clinical trial is in progress. Methionyl growth hormone (mGH) showed no effect on survival, disease progression and muscular strength. MGH was administered at a fixed dose and peripheral production of IGF-I appeared to be normal. We propose a double-blind trial of Growth Hormone (GH) as add-on therapy to Riluzole, with an individually regulated dose based on the peripheral response of IGF-I. Aim of our study is to determine if the add-on of GH to treatment with Riluzole is able to reduce neuronal loss in the motor cortex of ALS patients. As secondary objectives, effect of GH on mortality, QoL, and motor function will be assessed.
Interventions
The initial dose will be 2U s.c. every other day. The dose will be progressively increased to reach 1.5-2x the normal levels of IGF-I.
DRUGPlacebo
Same as for Growth hormone group
Sponsors
Istituto Biostrutture e Immagini, CNR Naples
Agenzia Italiana del Farmaco
Federico II University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Definite/probable ALS according to El Escorial criteria * Aged \> 40, \< 85 years * Progression from onset * Disease duration ≤3 years * Treatment with Riluzole
Exclusion criteria
* Rapid disease progression in the first 6 months after diagnosis * Patients with tracheostomy and/or Gastrostomy * Disease duration \> 3 years * Patient with exclusive bulbar or 2° motorneuron involvement * Hepatic/renal failure * Pregnant or breastfeeding * Signs of active neoplasia * Complicated Diabetes * Severe hypertension * Unable to undergo MRI exams
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint is the N-acetylaspartate/Creatine ratio in the motor cortex assessed with magnetic resonance spectroscopy. | 0, 6 and 12 months after treatment start |
Secondary
| Measure | Time frame |
|---|---|
| Difference in mortality between groups | 12 months |
| Difference in the ALS-FRS score (motor function scale) | 0, 6, and 12 months after treatment start |
| Difference in the SF-36 score (quality of life ) | 0, 6, and 12 monthst after treatmetn start |
| Safety and tolerability | 12 months |
Countries
Italy
Outcome results
None listed