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

NCT ID: NCT00035815

Last Updated: 2013-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 330 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2007-12-31

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IGF-1

Insulin like growth factor, type 1 will be given 0.05 mg per kg body weight subcutaneously twice daily

Group Type: ACTIVE_COMPARATOR

Insulin like growth factor, type 1

Intervention Type: DRUG

0.05 mg per kg body weight given subcutaneously twice daily

Placebo

Placebo arm

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Insulin like growth factor, type 1

0.05 mg per kg body weight given subcutaneously twice daily

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Mycotrophin

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

ALS Association

OTHER

Sponsor Role: collaborator

Cephalon

INDUSTRY

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic

Principal Investigators

Eric Sorenson, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Mayo Clinic

Locations

Mayo Clinic in Scottsdale

Scottsdale, Arizona, United States

California Pacific Medical Center

San Francisco, California, United States

Mayo Clinic in Jacksonville

Jacksonville, Florida, United States

Emory University

Atlanta, Georgia, United States

Indiana University

Indianapolis, Indiana, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Henry Ford Hospital

Detroit, Michigan, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Mississippi

Jackson, Mississippi, United States

Beth Israel Medical Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

University of Pennsylvania, Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Methodist Hospital

Houston, Texas, United States

West Virginia University

Morgantown, West Virginia, United States

Froedtert and Medical College Clinics

Milwaukee, Wisconsin, United States

University of Puerto Rico

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

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. No abstract available.

Reference Type: BACKGROUND

PMID: 19822878 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19029516 (View on PubMed)

Related Links

http://www.alsa.org

The ALS Association website.

Other Identifiers

R01NS042759

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1461-01

Identifier Type: -

Identifier Source: org_study_id