Safety and Efficacy Study of IGF-1 in Duchenne Muscular Dystrophy

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT01207908
• Collaborator: Ipsen (Industry), Charley's Fund (Other)
• Enrollment: 44
• Location: 1
• Arms: 2
• Actual Duration (Months): 31
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether IGF-1 therapy improves or preserves muscle function in Duchenne Muscular Dystrophy (DMD).

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: IGF-1	Phase 1/Phase 2

Detailed Description

Detailed Description:

DMD is a progressive degenerative muscle disorder for which there is no current cure. Glucocorticoids (GC) are often used to improve motor function and survival but have significant side effects such as growth failure, weight gain, insulin resistance and osteoporosis. IGF-1 stimulates both the proliferation and differentiation of skeletal muscle cells and is thus important for muscle repair and regeneration. IGF-1 offers potential as a therapeutic agent for DMD as it may improve or preserve motor function and reduce GC side effects such as growth failure and insulin resistance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: IGF-1 Therapy and Muscle Function in Duchenne Muscular Dystrophy
• Actual Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IGF-1 IGF-1 plus standard steroid treatment	Drug: IGF-1; IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.; Other Names: Increlex (mecasermin [rDNA origin] injection)
No Intervention: Standard steroid treatment alone Standard daily steroid treatment for DMD

Outcome Measures

Primary Outcome Measures

1. Difference in 6-Minute Walk Distance Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline [6 months]

   Outcome Measure Data Table shows change of 6-Minute Walk Distance at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1).

Secondary Outcome Measures

1. Difference in Height Velocity Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline [6 months]

   Outcome Measure Data Table shows change of height velocity at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1).

2. Difference in North Star Ambulatory Assessment (NSAA) Score Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline [6 months]

   Outcome Measure Data Table shows change of North Star Ambulatory Assessment (NSAA) score at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1). The NSAA is a 17-item scale that grades performance of various functional skills on a scale from 0 (unable), 1 (complete independently but with modifications), and 2 (complete without compensation). The range of NSAA score is from 0 to 34. The higher score indicates better motor function.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• DMD diagnosed with mutational testing and/or complete absence of dystrophin on muscle biopsy

• Proximal pelvic girdle weakness (Gower's maneuver, difficulty with arising from floor and going up steps)

• Male

• Age > 5 years of age

• Bone maturation (assess by bone age x-ray): </= 11 years of age

• Daily GC (prednisone or deflazacort) therapy for > 12 months

• Ambulatory

• Informed consent

• Willingness and ability to comply with all protocol requirements and procedures

Exclusion Criteria:

• Current or prior treatment with growth hormone or IGF-1 therapy

• Non-ambulatory

• Pubertal (based on clinical Tanner staging examination)

• Congestive cardiac failure

• History of intracranial hypertension

• Daytime ventilatory dependence (non-invasive or tracheostomy)

• Concomitant therapy - any other medications/supplements that would be considered, in the opinion of the investigators, to affect muscle function, need to have been started 3 months prior to enrollment

• Patients enrolled in other clinical drug trials

• Any physical or mental conditions which may, in the investigators'opinions, render the subject unable to complete the tasks of the study appropriately

• There will be no selection by ethnicity

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati
• Ipsen
• Charley's Fund

Investigators

• Principal Investigator: Meilan Rutter, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Genetics Home Reference
• Duchenne and Becker Muscular Dystrophy
• Muscular Dystrophy
• Medline

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT01207908
• Other Study ID Numbers: 2010-1491
• First Posted: Sep 23, 2010
• Last Update Posted: Jan 20, 2021
• Last Verified: Dec 1, 2020

• Keywords provided by Children's Hospital Medical Center, Cincinnati: DMD; Duchenne Muscular Dystrophy; Insulin like growth factor; 6 minute walk test
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne; Mecasermin

Study Results

Participant Flow

Arm/Group Title	IGF-1	Standard Steroid Treatment Alone
Arm/Group Description	IGF-1 plus standard steroid treatment IGF-1: IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.	Once daily steroid treatment (Deflazacort or Prednisone) administered orally for DMD.
Period Title: Overall Study
STARTED	22	22
COMPLETED	17	21
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	IGF-1	Standard Steroid Treatment Alone	Total
Arm/Group Description	IGF-1 plus standard steroid treatment IGF-1: IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.	Standard daily steroid treatment for DMD	Total of all reporting groups
Overall Participants	17	21	38
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.56 (1.28)	8.70 (1.79)	8.64 (1.67)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	17 100%	21 100%	38 100%

Outcome Measures

1. Primary Outcome

Title	Difference in 6-Minute Walk Distance Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline
Description	Outcome Measure Data Table shows change of 6-Minute Walk Distance at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IGF-1	Standard Steroid Treatment Alone
Arm/Group Description	IGF-1 plus standard steroid treatment IGF-1: IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.	Once daily steroid treatment (Deflazacort or Prednisone) administered orally for DMD.
Measure Participants	17	21
Mean (Standard Deviation) [meters]	3.4 (32.4)	-5.1 (50.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IGF-1, Standard Steroid Treatment Alone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.5
	Confidence Interval	(2-Sided) 95%; -37.1 to 20.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Difference in Height Velocity Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline
Description	Outcome Measure Data Table shows change of height velocity at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IGF-1	Standard Steroid Treatment Alone
Arm/Group Description	IGF-1 plus standard steroid treatment IGF-1: IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.	Once daily steroid treatment (Deflazacort or Prednisone) administered orally for DMD.
Measure Participants	17	21
Mean (Standard Deviation) [cm/year]	2.60 (1.64)	-0.06 (1.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IGF-1, Standard Steroid Treatment Alone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.66
	Confidence Interval	(2-Sided) 95%; -3.78 to -1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Difference in North Star Ambulatory Assessment (NSAA) Score Between Groups (Control Minus IGF-1) for Change at 6 Months Versus Baseline
Description	Outcome Measure Data Table shows change of North Star Ambulatory Assessment (NSAA) score at 6 months versus baseline in each arm. The Statistical Analysis section shows the 6-month difference between the 2 arms (control minus IGF-1). The NSAA is a 17-item scale that grades performance of various functional skills on a scale from 0 (unable), 1 (complete independently but with modifications), and 2 (complete without compensation). The range of NSAA score is from 0 to 34. The higher score indicates better motor function.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IGF-1	Standard Steroid Treatment Alone
Arm/Group Description	IGF-1 plus standard steroid treatment IGF-1: IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.	Once daily steroid treatment (Deflazacort or Prednisone) administered orally for DMD.
Measure Participants	17	21
Mean (Standard Deviation) [score on a scale]	-0.94 (2.41)	-0.4 (3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IGF-1, Standard Steroid Treatment Alone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95%; -1.26 to 2.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	IGF-1		Standard Steroid Treatment Alone
Arm/Group Description	IGF-1 plus standard steroid treatment IGF-1: IGF-1 will be administered once daily by subcutaneous injection every morning with breakfast. Duration 6 months.		Standard daily steroid treatment for DMD
All Cause Mortality
	IGF-1		Standard Steroid Treatment Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Serious Adverse Events
	IGF-1		Standard Steroid Treatment Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		0/22 (0%)
Nervous system disorders
Intracranial hypertension	1/22 (4.5%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	IGF-1		Standard Steroid Treatment Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/22 (90.9%)		21/22 (95.5%)
Gastrointestinal disorders
Nausea and vomiting	7/22 (31.8%)		5/22 (22.7%)
General disorders
fever	2/22 (9.1%)		3/22 (13.6%)
Musculoskeletal and connective tissue disorders
lipohypertrophy	4/22 (18.2%)		0/22 (0%)
Foot pain	1/22 (4.5%)		1/22 (4.5%)
Finger injury	1/22 (4.5%)		1/22 (4.5%)
Leg injury	1/22 (4.5%)		0/22 (0%)
Back pain	1/22 (4.5%)		3/22 (13.6%)
Finger infection	1/22 (4.5%)		0/22 (0%)
Leg pain	2/22 (9.1%)		4/22 (18.2%)
Arm weakness	1/22 (4.5%)		0/22 (0%)
Leg numbness	1/22 (4.5%)		0/22 (0%)
Nervous system disorders
Headache	11/22 (50%)		9/22 (40.9%)
seizure	0/22 (0%)		1/22 (4.5%)
papilledema	1/22 (4.5%)		0/22 (0%)
Skin and subcutaneous tissue disorders
stinging at injection site	3/22 (13.6%)		0/0 (NaN)
rash and skin welt	3/22 (13.6%)		1/22 (4.5%)

Limitations/Caveats

Small sample size and short duration, Open-label study.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.