Back to resultsInsulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
Primary Purpose
Amyotrophic Lateral Sclerosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Insulin like growth factor, type 1
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring amyotrophic lateral sclerosis, ALS, progressive weakness, insulin-like growth factor-1, IGF-I, Myotrophin
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.
Sites / Locations
- Mayo Clinic in Scottsdale
- California Pacific Medical Center
- Mayo Clinic in Jacksonville
- Emory University
- Indiana University
- University of Michigan Medical Center
- Henry Ford Hospital
- Hennepin County Medical Center
- Mayo Clinic
- University of Mississippi
- Beth Israel Medical Center
- University of Rochester Medical Center
- University of Cincinnati
- Cleveland Clinic
- Ohio State University
- University of Pennsylvania, Pennsylvania Hospital
- Methodist Hospital
- West Virginia University
- Froedtert and Medical College Clinics
- University of Puerto Rico
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
IGF-1
Placebo
Arm Description
Insulin like growth factor, type 1 will be given 0.05 mg per kg body weight subcutaneously twice daily
Placebo arm
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT00035815
First Posted
May 6, 2002
Last Updated
February 13, 2013
Sponsor
Mayo Clinic
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), ALS Association, Cephalon
1. Study Identification
Unique Protocol Identification Number
NCT00035815
Brief Title
Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
Official Title
Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
June 2003 (undefined)
Primary Completion Date
August 2007 (Actual)
Study Completion Date
December 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Mayo Clinic
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), ALS Association, Cephalon
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
amyotrophic lateral sclerosis, ALS, progressive weakness, insulin-like growth factor-1, IGF-I, Myotrophin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
330 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IGF-1
Arm Type
Active Comparator
Arm Description
Insulin like growth factor, type 1 will be given 0.05 mg per kg body weight subcutaneously twice daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo arm
Intervention Type
Drug
Intervention Name(s)
Insulin like growth factor, type 1
Other Intervention Name(s)
Mycotrophin
Intervention Description
0.05 mg per kg body weight given subcutaneously twice daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of Change in Composite Manual Muscle Testing (MMT) Score
Description
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).
Time Frame
Baseline and 24 months
Secondary Outcome Measure Information:
Title
Number of Participants Alive and Tracheostomy-free at 24 Months
Description
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.
Time Frame
baseline to 24 months
Title
Rate of Change in ALS Functional Rating Scale.
Description
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.
Time Frame
Baseline and 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Sorenson, M.D.
Organizational Affiliation
Department of Neurology, Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Scottsdale
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Mayo Clinic in Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Michigan Medical Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Hennepin County Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Mississippi
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Beth Israel Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pennsylvania, Pennsylvania Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
West Virginia University
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Froedtert and Medical College Clinics
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
University of Puerto Rico
City
San Juan
ZIP/Postal Code
00935
Country
Puerto Rico
12. IPD Sharing Statement
Citations:
PubMed Identifier
19822878
Citation
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.
Results Reference
background
PubMed Identifier
19029516
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, 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.
Results Reference
result
Links:
URL
http://www.alsa.org
Description
The ALS Association website.
Learn more about this trial
Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
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