Amyotrophic Lateral SclerosisPhase 3NCT00035815
Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
A Phase 3 study testing Insulin like growth factor, type 1 in people with Amyotrophic Lateral Sclerosis, run by Mayo Clinic at 20 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Insulin like growth factor, type 1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 330 participants
- Where
- 20 sitesin 2 countries
- Study dates
- Jun 2003to Dec 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States19 sites
University of Michigan Medical Center
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
University of Cincinnati
Cincinnati, Ohio, 45219
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43210
Henry Ford Hospital
Detroit, Michigan, 48202
Methodist Hospital
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
University of Mississippi
Jackson, Mississippi, 39216
Mayo Clinic in Jacksonville
Jacksonville, Florida, 32224
Froedtert and Medical College Clinics
Milwaukee, Wisconsin, 53226
Hennepin County Medical Center
Minneapolis, Minnesota, 55404
West Virginia University
Morgantown, West Virginia, 26506
Beth Israel Medical Center
New York, New York, 10003
University of Pennsylvania, Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester Medical Center
Rochester, New York, 14642
California Pacific Medical Center
San Francisco, California, 94115
Mayo Clinic in Scottsdale
Scottsdale, Arizona, 85259
About this study
Official title: Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS)
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.
Read the 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
- Being tested
- Insulin like growth factor, type 1, Placebo
- Keywords
- amyotrophic lateral sclerosis, ALS, progressive weakness, insulin-like growth factor-1, IGF-I, Myotrophin
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin like growth factor, type 1Drug
Also called Mycotrophin
0.05 mg per kg body weight given subcutaneously twice daily
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| IGF-1 | Active comparator | Insulin like growth factor, type 1 will be given 0.05 mg per kg body weight subcutaneously twice daily Receives: Drug: Insulin like growth factor, type 1 |
| Placebo | Placebo comparator | Placebo arm Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline and 24 months
Secondary outcomes (2)
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.
Measured: 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.
Measured: Baseline and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2002 (estimated)
- Study startJun 2003
- Primary completionAug 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 330 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), ALS Association, Cephalon
- Investigators
- Eric Sorenson, M.D., Principal investigator, Department of Neurology, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00035815
- Sponsor's protocol ID
- 1461-01
- Other IDs
- R01NS042759
- Status last verified
- Feb 2013
- First submitted
- 6 May 2002
- Last updated
- 15 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19822878Sorenson 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.
PubMed 19029516
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS)
- ClinicalTrials.gov ID
- NCT00035815
- Acronym / sponsor ID
- 1461-01
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- amyotrophic lateral sclerosis, ALS, progressive weakness, insulin-like growth factor-1, IGF-I, Myotrophin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 330 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), ALS Association, Cephalon
- Study start
- Jun 2003
- Primary completion
- Aug 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 7 May 2002 (estimated)
- Results
- Posted 15 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IGF-1 | Active comparator | Drug: Insulin like growth factor, type 1Insulin like growth factor, type 1 will be given 0.05 mg per kg body weight subcutaneously twice daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo arm |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (11 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin like growth factor, type 1Also: Mycotrophin0.05 mg per kg body weight given subcutaneously twice daily | Drug | IGF-1 |
| PlaceboThe 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. | Drug | Placebo |
Primary outcome
Rate of Change in Composite Manual Muscle Testing (MMT) Score
Time frame: Baseline and 24 months
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).
2 secondary outcomes
Number of Participants Alive and Tracheostomy-free at 24 Months
Time frame: baseline to 24 months
Rate of Change in ALS Functional Rating Scale.
Time frame: Baseline and 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19822878Howe 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 publication: PubMed 19029516Sorenson 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.
- The ALS Association website.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Sorenson, M.D. principal investigator
Department of Neurology, Mayo Clinic
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Insulin like growth factor, type 1 in people with Amyotrophic Lateral Sclerosis, run by Mayo Clinic at 20 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Feb 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Change in Composite Manual Muscle Testing (MMT) Score (time frame: Baseline and 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00035815, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2013.