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

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: July 2009

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.

Intervention(s) in this Clinical Trial

• Drug: Growth Hormone (Somatropin)
  • 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.
• Drug: Placebo
  • Same as for Growth hormone group

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Patients randomly assigned to treatment
• Placebo Comparator: 2
  • Patients randomly assigned to placebo

Primary Measures

• Primary endpoint is the N-acetylaspartate/Creatine ratio in the motor cortex assessed with magnetic resonance spectroscopy.
  • Time Frame: 0, 6 and 12 months after treatment start
    Safety Issue?: No

Secondary Measures

• Difference in mortality between groups
  • Time Frame: 12 months
    Safety Issue?: No
• Difference in the ALS-FRS score (motor function scale)
  • Time Frame: 0, 6, and 12 months after treatment start
    Safety Issue?: No
• Difference in the SF-36 score (quality of life )
  • Time Frame: 0, 6, and 12 monthst after treatmetn start
    Safety Issue?: Yes
• Safety and tolerability
  • Time Frame: 12 months
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Federico II University

Overall Clinical Trial Officials and Contacts

Alessandro Filla, MD Principal Investigator University "Federico II", Naples  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00635960

Study ID Number: SLA_GH_1

ClinicalTrials.gov Identifier: NCT00635960

Health Authority: Italy: Ministry of Health

Institute of Biostructure and Bioimaging, CNR Naples

University "Federico II", Naples

Policlinico "Federico II", Naples

AIFA