Clinical trial NCT00035815: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Amyotrophic Lateral Sclerosis
Keywords: amyotrophic lateral sclerosis
ALS
progressive weakness
insulin-like growth factor-1
IGF-I
Myotrophin
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: ALS Association
name: Cephalon
First posted: 2002-05-07
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Rate of Change in Composite Manual Muscle Testing (MMT) Score
timeFrame: Baseline and 24 months
Secondary outcomes:
measure: Number of Participants Alive and Tracheostomy-free at 24 Months
timeFrame: baseline to 24 months
measure: Rate of Change in ALS Functional Rating Scale.
timeFrame: Baseline and 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Scottsdale
state: Arizona
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic in Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi
state: Mississippi
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania, Pennsylvania Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Methodist Hospital
state: Texas
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Froedtert and Medical College Clinics
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
Study officials:
affiliation: Department of Neurology, Mayo Clinic
name: Eric Sorenson, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.