Trial Outcomes & Findings for Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial (NCT NCT00035815)

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

330 participants

Primary outcome timeframe

Baseline and 24 months

Results posted on

2013-02-15

Participant Flow

Subjects recruited from 20 medical centers from June 2003 to August 2005.

Patients were randomized and initiated on treatment at the time of enrollment.

Participant milestones

Participant milestones
Measure	IGF-1 The insulin-like growth factor type 1 (IGF-1) arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.
Overall Study STARTED	167	163
Overall Study COMPLETED	150	152
Overall Study NOT COMPLETED	17	11

Reasons for withdrawal

Reasons for withdrawal
Measure	IGF-1 The insulin-like growth factor type 1 (IGF-1) arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.
Overall Study Withdrawal by Subject	17	11

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IGF-1 n=167 Participants The IGF-1 arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo n=163 Participants Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.	Total n=330 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	135 Participants n=93 Participants	129 Participants n=4 Participants	264 Participants n=27 Participants
Age, Categorical >=65 years	32 Participants n=93 Participants	34 Participants n=4 Participants	66 Participants n=27 Participants
Age Continuous	53.9 years STANDARD_DEVIATION 12.2 • n=93 Participants	54.8 years STANDARD_DEVIATION 11.2 • n=4 Participants	54.4 years STANDARD_DEVIATION 11.7 • n=27 Participants
Sex: Female, Male Female	57 Participants n=93 Participants	63 Participants n=4 Participants	120 Participants n=27 Participants
Sex: Female, Male Male	110 Participants n=93 Participants	100 Participants n=4 Participants	210 Participants n=27 Participants
Region of Enrollment United States	167 participants n=93 Participants	163 participants n=4 Participants	330 participants n=27 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	IGF-1 n=167 Participants The IGF-1 arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo n=163 Participants Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.
Rate of Change in Composite Manual Muscle Testing (MMT) Score	0.44 MMT units per month Standard Deviation 0.57	0.39 MMT units per month Standard Deviation 0.39

SECONDARY outcome

Timeframe: baseline to 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.

Outcome measures

Outcome measures
Measure	IGF-1 n=167 Participants The IGF-1 arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo n=163 Participants Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.
Number of Participants Alive and Tracheostomy-free at 24 Months	93 participants Interval 0.77 to 1.4	90 participants Interval 1.0 to 1.0

SECONDARY outcome

Timeframe: Baseline and 24 months

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.

Outcome measures

Outcome measures
Measure	IGF-1 n=167 Participants The IGF-1 arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo n=163 Participants Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.
Rate of Change in ALS Functional Rating Scale.	2.5 Units on a scale per month Standard Deviation 3.2	2.2 Units on a scale per month Standard Deviation 2.1

Adverse Events

IGF-1

Serious events: 18 serious events

Other events: 103 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 92 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IGF-1 n=167 participants at risk The IGF-1 arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo n=163 participants at risk Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.
Vascular disorders Thrombotic events	10.8% 18/167 • Number of events 18 • 2 years of follow-up	7.4% 12/163 • Number of events 12 • 2 years of follow-up

Other adverse events

Other adverse events
Measure	IGF-1 n=167 participants at risk The IGF-1 arm was the active treatment group. They received 0.05 mg/kg body weight administered subcutaneously twice daily.	Placebo n=163 participants at risk Placebo group received the equal volume (based on kg of body weight) of the inert suspension vehicle in which the IGF-1 was suspended.
Skin and subcutaneous tissue disorders Site reactions	52.7% 88/167 • Number of events 88 • 2 years of follow-up	56.4% 92/163 • Number of events 92 • 2 years of follow-up
Nervous system disorders Headache	13.2% 22/167 • Number of events 22 • 2 years of follow-up	13.5% 22/163 • Number of events 22 • 2 years of follow-up
Hepatobiliary disorders Hepatotoxicity	8.4% 14/167 • Number of events 14 • 2 years of follow-up	4.9% 8/163 • Number of events 8 • 2 years of follow-up
Eye disorders Change in visual acuity	13.8% 23/167 • Number of events 23 • 2 years of follow-up	12.3% 20/163 • Number of events 20 • 2 years of follow-up
Metabolism and nutrition disorders Abnormal blood chemistries (other than liver)	6.0% 10/167 • Number of events 10 • 2 years of follow-up	8.0% 13/163 • Number of events 13 • 2 years of follow-up
Endocrine disorders Hypoglycemia	12.6% 21/167 • Number of events 21 • 2 years of follow-up	5.5% 9/163 • Number of events 9 • 2 years of follow-up
Psychiatric disorders Depression	61.7% 103/167 • Number of events 103 • 2 years of follow-up	56.4% 92/163 • Number of events 92 • 2 years of follow-up
Respiratory, thoracic and mediastinal disorders Respiratory failure	32.9% 55/167 • Number of events 55 • 2 years of follow-up	30.7% 50/163 • Number of events 50 • 2 years of follow-up

Additional Information

Eric J. Sorenson, MD

Mayo Clinic

Phone: 507 538-1037

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place