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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00035815
• Other study ID #: 1461-01
• Secondary ID: R01NS042759
• Status: Completed
• Phase: Phase 3
• First received: May 6, 2002
• Last updated: February 13, 2013
• Start date: June 2003
• Est. completion date: December 2007

Study information

• Verified date: February 2013
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 330
• Est. completion date: December 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Insulin like growth factor, type 1
0.05 mg per kg body weight given subcutaneously twice daily
• 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.

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
Mayo Clinic	ALS Association, Cephalon, National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (2)

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. — View Citation

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Change in Composite Manual Muscle Testing (MMT) Score	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).	Baseline and 24 months	No
Secondary	Number of Participants Alive and Tracheostomy-free at 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.	baseline to 24 months	Yes
Secondary	Rate of Change in ALS Functional Rating Scale.	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.	Baseline and 24 months	No

External Links

•   The ALS Association website.