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

Phase 3

Completed

Brief Summary: The purpose of this multicenter study is to determine if insulin-like growth factor-1 (IGF-I) slows the progressive weakness in amyotrophic lateral sclerosis (ALS) patients. Study participants will be followed for 2 years once enrolled. They will receive either placebo or the active IGF-I. Examinations will take place at approximately 6-month intervals.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Patients entering this study will not:

Have any of the following conditions:renal disease (Creatine > 2.0) or other active systemic disease
Have any clinically significant abnormalities on the prestudy laboratory evaluation, physical examination, ECG, chest x-ray or ophthalmologic exam.
Have any clinically significant medical condition (e.g., within six months of baseline, had myocardial infarction, angina pectoris, and/or congestive heart failure) that, in the opinion of the investigator, would compromise the safety of patient.
Have Type I or Type II diabetes.
Have a history of cancer including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline) and carcinoma in-situ of the cervix (women only).
Have used an investigational drug within 30 days of baseline visit.
Have had a tracheostomy.
Have a Beck's Depression Inventory score * 12.
Have legal residency outside of the United States or Canada.
Be pregnant or breast-feeding.

Arm && Interventions

Group	Intervention	Description
IGF-1	Insulin like growth factor, type 1	Insulin like growth factor, type 1 will be given 0.05 mg per kg body weight subcutaneously twice daily
Placebo	Placebo	Placebo arm

Primary Outcome Measures

Name	Time	Method
Rate of Change in Composite Manual Muscle Testing (MMT) Score	Baseline and 24 months	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants Alive and Tracheostomy-free at 24 Months	baseline to 24 months	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.	Baseline and 24 months	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.

Locations (20): University of Mississippi
🇺🇸
Jackson, Mississippi, United States
Ohio State University
🇺🇸
Columbus, Ohio, United States
University of Pennsylvania, Pennsylvania Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
West Virginia University
🇺🇸
Morgantown, West Virginia, United States
Mayo Clinic in Jacksonville
🇺🇸
Jacksonville, Florida, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Beth Israel Medical Center
🇺🇸
New York, New York, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Mayo Clinic in Scottsdale
🇺🇸
Scottsdale, Arizona, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
University of Puerto Rico
🇵🇷
San Juan, Puerto Rico
University of Michigan Medical Center
🇺🇸
Ann Arbor, Michigan, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
California Pacific Medical Center
🇺🇸
San Francisco, California, United States
Indiana University
🇺🇸
Indianapolis, Indiana, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Methodist Hospital
🇺🇸
Houston, Texas, United States
Froedtert and Medical College Clinics
🇺🇸
Milwaukee, Wisconsin, United States