Growth Hormone in Amyotrophic Lateral Sclerosis

Condition(s) targeted: Amyotrophic Lateral Sclerosis

Intervention: Growth Hormone (Somatropin) (Drug); Placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Federico II University

Official(s) and/or principal investigator(s):
Alessandro Filla, MD, Principal Investigator, Affiliation: University "Federico II", Naples

Overall contact:
Francesco Saccà, MD, Phone: 39-34-7073-4774, Ext: +39, Email: francesco.sacca@unina.it

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.

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

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

Primary outcome: Primary endpoint is the N-acetylaspartate/Creatine ratio in the motor cortex assessed with magnetic resonance spectroscopy.

Secondary outcome:

Difference in mortality between groups

Difference in the ALS-FRS score (motor function scale)

Difference in the SF-36 score (quality of life )

Safety and tolerability

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.

Minimum age: 40 Years. Maximum age: 85 Years. Gender(s): Both.

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

Francesco Saccà, MD, Phone: 39-34-7073-4774, Ext: +39, Email: francesco.sacca@unina.it

Diparimento di Scienze Neurologiche, Naples 80131, Italy; Recruiting
Francesco Saccà, MD, Phone: 39-34-7073-4774, Ext: +39, Email: francesco.sacca@unina.it
Vincenzo Brescia Morra, MD, Sub-Investigator
Francesco Saccà, MD, Sub-Investigator
Carlo Rinaldi, MD, Sub-Investigator
Tecla Tucci, MD, Sub-Investigator
Alessandro Filla, MD, Principal Investigator

Istituto Biostrutture e Bioimmagini, Consiglio Nazionale delle Ricerche, Naples 80131, Italy; Active, not recruiting

Institute of Biostructure and Bioimaging, CNR Naples

University "Federico II", Naples

Policlinico "Federico II", Naples

AIFA

Starting date: March 2007
Ending date: December 2009
Last updated: April 14, 2008