Growth Hormone in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00635960
• Other study ID #: SLA_GH_1
• Status: Completed
• Phase: Phase 2
• First received: March 3, 2008
• Last updated: May 25, 2010
• Start date: March 2007
• Est. completion date: May 2010

Study information

• Verified date: May 2010
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

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.
• Placebo
Same as for Growth hormone group

Locations

Country	Name	City	State
Italy	Diparimento di Scienze Neurologiche	Naples
Italy	Istituto Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche	Naples

Sponsors (3)

Lead Sponsor	Collaborator
Federico II University	Agenzia Italiana del Farmaco, Istituto Biostrutture e Immagini, CNR Naples

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Difference in mortality between groups		12 months	No
Secondary	Difference in the ALS-FRS score (motor function scale)		0, 6, and 12 months after treatment start	No
Secondary	Difference in the SF-36 score (quality of life )		0, 6, and 12 monthst after treatmetn start	Yes
Secondary	Safety and tolerability		12 months	Yes

External Links

•   AIFA
•   Institute of Biostructure and Bioimaging, CNR Naples
•   Policlinico "Federico II", Naples
•   University "Federico II", Naples