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

Study Description

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Insulin like growth factor, type 1; Drug: Placebo	Phase 3

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.

Study Design

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	330 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS)
Study Start Date :	June 2003
Actual Primary Completion Date :	August 2007
Actual Study Completion Date :	December 2007

Arms and Interventions

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: IGF-1; Insulin like growth factor, type 1 will be given 0.05 mg per kg body weight subcutaneously twice daily	Drug: Insulin like growth factor, type 1; 0.05 mg per kg body weight given subcutaneously twice daily; Other Name: Mycotrophin
Placebo Comparator: Placebo; Placebo arm	Drug: Placebo; The placebo represented the inert suspension vehicle for the IGF-1. It was given as equal volume as the active drug based upon body weight, subcutaneously twice daily.

Outcome Measures

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Rate of Change in Composite Manual Muscle Testing (MMT) Score [ Time Frame: 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 :

1. Number of Participants Alive and Tracheostomy-free at 24 Months [ Time Frame: 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.
2. Rate of Change in ALS Functional Rating Scale. [ Time Frame: 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.

Eligibility Criteria

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Patients entering this study:

• Are between the ages of 18-80 years old.
• Legal residents of the United States or Canada.
• Have a history of a chronic onset of a progressive motor weakness of less than 24 months duration.
• Fulfill El Escorial criteria of probable or definite ALS.
• If female, are surgically sterile, two years postmenopausal, or if of child-bearing potential, must be using a medically acceptable method of birth control and agree to continue use of this method for the duration of the study. Acceptable methods include a barrier method with spermicide, oral contraceptives (normal doses are acceptable; low dose oral contraceptives or contraceptive implants must be used with a barrier method), intrauterine device (IUD), or abstinence. Have a negative pregnancy test.
• Are able to comply with protocol requirements.
• Can provide written informed consent.
• Have a manual muscle testing score of less than 8.
• Have a forced vital capacity by pulmonary function testing *60% predicted.

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.

Contacts and Locations

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Arizona
Mayo Clinic in Scottsdale
Scottsdale, Arizona, United States, 85259
United States, California
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Florida
Mayo Clinic in Jacksonville
Jacksonville, Florida, United States, 32224
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55404
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi
Jackson, Mississippi, United States, 39216
United States, New York
Beth Israel Medical Center
New York, New York, United States, 10003
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania, Pennsylvania Hospital
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Methodist Hospital
Houston, Texas, United States, 77030
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Froedtert and Medical College Clinics
Milwaukee, Wisconsin, United States, 53226
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00935

Sponsors and Collaborators

Mayo Clinic

National Institute of Neurological Disorders and Stroke (NINDS)

ALS Association

Cephalon

Investigators

Principal Investigator:	Eric Sorenson, M.D.	Department of Neurology, Mayo Clinic

More Information

Go to 

Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

The ALS Association website. 

Publications of Results:

Sorenson EJ, Windbank AJ, Mandrekar JN, Bamlet WR, Appel SH, Armon C, Barkhaus PE, Bosch P, Boylan K, David WS, Feldman E, Glass J, Gutmann L, Katz J, King W, Luciano CA, McCluskey LF, Nash S, Newman DS, Pascuzzi RM, Pioro E, Sams LJ, Scelsa S, Simpson EP, Subramony SH, Tiryaki E, Thornton CA. Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology. 2008 Nov 25;71(22):1770-5. doi: 10.1212/01.wnl.0000335970.78664.36.

Other Publications:

Howe CL, Bergstrom RA, Horazdovsky BF. Subcutaneous IGF-1 is not beneficial in 2-year ALS trial. Neurology. 2009 Oct 13;73(15):1247; author reply 1247-8. doi: 10.1212/WNL.0b013e3181b26ae6.

Responsible Party:	Eric Sorenson, M.D., Department of Neurology, Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00035815 History of Changes
Other Study ID Numbers:	1461-01; R01NS042759 ( U.S. NIH Grant/Contract )
First Posted:	May 7, 2002
Results First Posted:	February 15, 2013
Last Update Posted:	February 15, 2013
Last Verified:	February 2013

Keywords provided by Mayo Clinic:

amyotrophic lateral sclerosis; ALS; progressive weakness	insulin-like growth factor-1; IGF-I; Myotrophin

Additional relevant MeSH terms:

Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies	Metabolic Diseases; Insulin, Globin Zinc; Insulin; Mitogens; Mecasermin; Hypoglycemic Agents; Physiological Effects of Drugs; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Growth Substances