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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Insulin like growth factor, type 1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IGF-1<br>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<br>* 0.05 mg per kg body weight given subcutaneously twice daily<br>* Other names: Mycotrophin;|
| Placebo Comparator: Placebo<br>Placebo arm | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, amyotrophic lateral sclerosis, progressive weakness, insulin-like growth factor-1, IGF-I, Myotrophin