Clinical trial NCT00635960: Growth Hormone in Amyotrophic Lateral Sclerosis
Official title: Efficacy, Safety and Tolerability of Growth Hormone in Patients With Amyotrophic Lateral Sclerosis as add-on Therapy to Riluzole
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
ALS
Growth Hormone
IGF-I
Lead sponsor: Federico II University
Sponsor class: OTHER
Collaborators: name: Istituto Biostrutture e Immagini, CNR Naples
name: Agenzia Italiana del Farmaco
First posted: 2008-03-14
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary endpoint is the N-acetylaspartate/Creatine ratio in the motor cortex assessed with magnetic resonance spectroscopy.
timeFrame: 0, 6 and 12 months after treatment start
Secondary outcomes:
measure: Difference in mortality between groups
timeFrame: 12 months
measure: Difference in the ALS-FRS score (motor function scale)
timeFrame: 0, 6, and 12 months after treatment start
measure: Difference in the SF-36 score (quality of life )
timeFrame: 0, 6, and 12 monthst after treatmetn start
measure: Safety and tolerability
timeFrame: 12 months
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Diparimento di Scienze Neurologiche
city: Naples
country: Italy
facility: Istituto Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche
Study officials:
affiliation: University "Federico II", Naples
name: Alessandro Filla, MD
role: PRINCIPAL_INVESTIGATOR
References: