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

This study has been completed.
Sponsor:
Collaborators:
ALS Association
Cephalon
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00035815
First received: May 6, 2002
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: Insulin like growth factor, type 1
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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.


Enrollment: 330
Study Start Date: June 2003
Study Completion Date: December 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00035815

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
ALS Association
Cephalon
Investigators
Principal Investigator: Eric Sorenson, M.D. Department of Neurology, Mayo Clinic
  More Information

Additional Information:
Publications:
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
Study First Received: May 6, 2002
Results First Received: November 17, 2009
Last Updated: February 13, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
amyotrophic lateral sclerosis
ALS
progressive weakness
insulin-like growth factor-1
IGF-I
Myotrophin

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
Mitogens
Insulin, Globin Zinc
Insulin
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2014