Growth Hormone in Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy, Safety and Tolerability of Growth Hormone in Patients With Amyotrophic Lateral Sclerosis as add-on Therapy to Riluzole

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Growth Hormone (Somatropin)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patients randomly assigned to treatment | Drug: Growth Hormone (Somatropin)<br>* 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.<br>* Other names: Saizen 8mg;|
| Placebo Comparator: 2<br>Patients randomly assigned to placebo | Drug: Placebo<br>* Same as for Growth hormone group<br>* Other names: Saizen 8mg placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, ALS, Growth Hormone, IGF-I