Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial

• Rate of Change in Composite Manual Muscle Testing (MMT) Score [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
  The primary outcome measure was the rate of change in the MMT score. MMT involved the examination of 34 muscle groups with standard positioning. The final MMT score represented an average of the 34 muscles examined, and ranged from 10 to 0(10 normal strength, 0 paralyzed). The individual muscle score was based on the medical research council (MRC) grading scale (1-5) modified to a 10 point system corresponding to the MRC modifications of plus and minus (5, 5-,4+,4,4-,3+,3, 3-,2,1,0; with 5 being normal strength and 0 paralyzed).
  
  

• Number of Participants Alive and Tracheostomy-free at 24 Months [ Time Frame: baseline to 24 months ] [ Designated as safety issue: Yes ]
  Patients who elected to proceed to tracheostomy were assessed the month of their procedure. Subjects who continuously utilized non-invasive positive pressure ventilation for greater than 10 days were assessed as being ventilator-dependent on the first day they began continuous Non Invasive Positive Pressure Ventilation (NIPPV). All subjects were followed for the 24 month time period.
  
  
• Rate of Change in ALS Functional Rating Scale. [ Time Frame: Baseline and 24 months ] [ Designated as safety issue: No ]
  The final secondary outcome measure was the rate of change in the ALS Functional Rating Scale (ALSFRS-r) score. The ALSFRS-r was completed at each visit (randomization and then at 3, 6, 12, 18 and 24 months post-randomization). This is a scale from 0 to 48 assessing functional impairment in 12 clinically relevant areas in ALS. Forty-eight is normal with full function and zero is total loss of function in all clinical functions. As with the MMT scores a score of 0 was imputed on the day of death. Analysis of the ALSFRS-r scores as a secondary outcome was performed in similar manner as MMT score.
  
  

The objective of this trial was to determine whether IGF-1 (MyotrophinTM) slows progression of weakness in amyotrophic lateral sclerosis (ALS). Three hundred thirty patients with ALS from 20 medical centers participated in this double blind, placebo-controlled two-year study. Half the patients received IGF-1 and the other half received placebo. The drug will be administered twice a day.

ALS is a neurodegenerative disorder that causes progressive muscle weakness and loss of motor neurons. IGF-1 is a neurotrophic factor essential for normal development of the nervous system and shows protection of motor neurons in animal models and cell culture systems. It is thought to block cell death pathways and promote muscle re-innervation and axonal growth and regeneration.