Growth Hormone in Amyotrophic Lateral Sclerosis - Full Text View

Sponsor:	Federico II University
Collaborators:	Istituto Biostrutture e Immagini, CNR Naples Agenzia Italiana del Farmaco
Information provided by:	Federico II University
ClinicalTrials.gov Identifier:	NCT00635960

Purpose

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.

Condition	Intervention	Phase
Amyotrophic Lateral Sclerosis	Drug: Growth Hormone (Somatropin) Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Efficacy, Safety and Tolerability of Growth Hormone in Patients With Amyotrophic Lateral Sclerosis as add-on Therapy to Riluzole

Resource links provided by NLM:

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

Drug Information available for: Somatropin Somatotropin

U.S. FDA Resources

Further study details as provided by Federico II University:

Primary Outcome 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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

Estimated Enrollment:	40
Study Start Date:	March 2007
Study Completion Date:	May 2010
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Patients randomly assigned to treatment	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. Other Name: Saizen 8mg
Placebo Comparator: 2 Patients randomly assigned to placebo	Drug: Placebo Same as for Growth hormone group Other Name: Saizen 8mg placebo

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

Ages Eligible for Study:	40 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00635960

Locations

Italy
Diparimento di Scienze Neurologiche
Naples, Italy, 80131
Istituto Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche
Naples, Italy, 80131

Sponsors and Collaborators

Federico II University

Istituto Biostrutture e Immagini, CNR Naples

Agenzia Italiana del Farmaco

Investigators

Principal Investigator:

Alessandro Filla, MD

University "Federico II", Naples

More Information

Additional Information:

Institute of Biostructure and Bioimaging, CNR Naples This link exits the ClinicalTrials.gov site

University "Federico II", Naples This link exits the ClinicalTrials.gov site

Policlinico "Federico II", Naples This link exits the ClinicalTrials.gov site

AIFA

No publications provided

Responsible Party:	Alessandro Filla, Prof., Dipartimento di Scienze Neurologiche, "Federico II" University, Naples
ClinicalTrials.gov Identifier:	NCT00635960 History of Changes
Other Study ID Numbers:	SLA_GH_1
Study First Received:	March 3, 2008
Last Updated:	May 25, 2010
Health Authority:	Italy: Ministry of Health

Keywords provided by Federico II University:

Amyotrophic Lateral Sclerosis
ALS
Growth Hormone
IGF-I

Additional relevant MeSH terms:

Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies

Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012