Clinical Trial of Growth Hormone in MPS I, II, and VI - Full Text View

Sponsor:	University of Minnesota - Clinical and Translational Science Institute
Information provided by:	University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:	NCT00748969

Purpose

The purpose of this study is to determine whether growth hormone is a safe and effective treatment for short stature in children with Mucopolysaccharidosis type I, II, and VI.

Condition	Intervention	Phase
Mucopolysaccharidosis Type I, II, and VI.	Drug: Somatropin (DNA origin)	Phase II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II/III, Randomized, Clinical Trial of the Effects of Nutropin AQ® on Growth and Bone Metabolism in Children With MPS I, II, and VI and Short Stature

Resource links provided by NLM:

Genetics Home Reference related topics: mucopolysaccharidosis type I

Drug Information available for: Somatropin Somatotropin

U.S. FDA Resources

Further study details as provided by University of Minnesota - Clinical and Translational Science Institute:

Primary Outcome Measures:

Change in growth velocity from baseline to end of study year 1. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety of Nutropin AQ® in children with MPS I, II, and VI. Safety endpoints are: • Physical examinations • Fundoscopic examinations • Adverse events • Radiographic examinations of spine and lower extremities [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Change in bone mineral density, content, and strength by DXA and pQCT, and change in serum markers of bone metabolism. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Change in mobility measured by force and gait measurements. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Change in muscle strength measured by Biodex and Hand Grip Dynamometer. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Change in neuropsychological functioning and brain volumetrics. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	34
Study Start Date:	November 2008
Estimated Study Completion Date:	September 2013
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Growth hormone treatment arm.	Drug: Somatropin (DNA origin) The study starting dose of Nutropin AQ® will be 0.48 mg/kg/week divided into daily SC injections. Nutropin AQ® will be administered by either the subject or, if unable to demonstrate competency in this, then by the guardian. To decrease the risk of increased intracranial hypertension, the dose in the first month of treatment will be decreased by 50% (0.24 mg/kg/week), and then increased to 0.48 mg/kg/week if tolerated well after 1 month.
2: No Intervention No growth hormone treatment in year 1; option for treatment in year 2 open-label period.	Drug: Somatropin (DNA origin) The study starting dose of Nutropin AQ® will be 0.48 mg/kg/week divided into daily SC injections. Nutropin AQ® will be administered by either the subject or, if unable to demonstrate competency in this, then by the guardian. To decrease the risk of increased intracranial hypertension, the dose in the first month of treatment will be decreased by 50% (0.24 mg/kg/week), and then increased to 0.48 mg/kg/week if tolerated well after 1 month.

Arms

Assigned Interventions

1: Experimental

Growth hormone treatment arm.

Drug: Somatropin (DNA origin)

The study starting dose of Nutropin AQ® will be 0.48 mg/kg/week divided into daily SC injections. Nutropin AQ® will be administered by either the subject or, if unable to demonstrate competency in this, then by the guardian. To decrease the risk of increased intracranial hypertension, the dose in the first month of treatment will be decreased by 50% (0.24 mg/kg/week), and then increased to 0.48 mg/kg/week if tolerated well after 1 month.

2: No Intervention

No growth hormone treatment in year 1; option for treatment in year 2 open-label period.

Drug: Somatropin (DNA origin)

The study starting dose of Nutropin AQ® will be 0.48 mg/kg/week divided into daily SC injections. Nutropin AQ® will be administered by either the subject or, if unable to demonstrate competency in this, then by the guardian. To decrease the risk of increased intracranial hypertension, the dose in the first month of treatment will be decreased by 50% (0.24 mg/kg/week), and then increased to 0.48 mg/kg/week if tolerated well after 1 month.

Detailed Description:

Although children with MPS I, II, and VI who are treated with Hematopoietic Cell Transplantation (HCT) and/or enzyme replacement therapy (ERT) are living into adulthood with good cognitive development, their quality of life is significantly impacted by their skeletal abnormalities (i.e., kyphosis, scoliosis, and genu valgum), contractures, and severe short stature. Here at the University of Minnesota we have seen some promising clinical outcomes in children with MPS IH whom we have treated with human growth hormone (hGH). There are currently no reports in the literature of the impact of treating children with MPS and short stature, with hGH on their growth velocity or characteristic skeletal abnormalities. This study will advance the care of these children by providing data in this yet unexplored area of pediatric medicine with the goal of improving the quality of life for these children by improving height, mobility, and neuropsychological functioning.

This is a Phase II/III randomized, single-center, 12 month clinical trial of growth hormone in male and female participants with MPS I, II, or VI, followed by 12 months open label. Participants with height ≤ -2 SDS for age and gender will be randomized for the first 12 months 1:1 to treatment or no treatment. At the conclusion of the 12 months, all subjects will be offered an additional 12 months of treatment.

Eligibility

Ages Eligible for Study:	5 Years to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

A parent or legally authorized representative must provide written informed consent and comply with study assessments for the full duration of the study.
Chronologic age ≥ 5 years and bone age ≤12 years
Diagnosis of MPS I, II, or VI
Height ≤ -2 SDS for age and gender
Ability to travel to study center for evaluations.
Ability of the participant to cooperate with study procedures, to notify a guardian of symptoms, and provide assent for participation in the study.

Exclusion Criteria:

History of treatment with hGH
Untreated pituitary deficiency
Pregnancy (positive urine pregnancy test) prior to enrollment in the study
Participation in another simultaneous medical intervention trial
Patients with closed epiphysis
Active neoplasm
Orthopedic procedure of the femur within the last 6 months.
Known or suspected allergy to trial product or related products.
Structural lesion on brain MRI resulting in brain compression
Any other social or medical condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study.
Obstructive sleep apnea without BiPAP or tonsillectomy/adenoidectomy treatment.
CNS shunt.
Abnormal cardiac function based on echocardiogram within 6 months prior to enrollment :
Ejection fraction less than 50%
Left ventricular chamber size greater than or less than 2 standard deviations of normal for body surface area
Left ventricular wall thickness greater than or less than 2 standard deviations of normal for body surface area
More than mild to moderate aortic insufficiency with abdominal aortic run-off
More than mild to moderate mitral insufficiency with pulmonary hypertension
Abnormal pulmonary function based on pulmonary function tests within 6 months prior to enrollment:
abnormal FVC < 80% of predicted for age, gender, and height
abnormal FEV1 < 80% predicted for age, gender, and height
abnormal FEV1/FVC
abnormal oxygen saturation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00748969

Contacts

Contact: Matthew Deyo	612-625-8246	deyo0021@umn.edu
Contact: Lynda E Polgreen, M.D.	612-624-4459	polgr001@umn.edu

Locations

United States, Minnesota
University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Matthew Deyo 612-625-8246 deyo0021@umn.edu
Principal Investigator: Lynda E Polgreen, M.D.

Sponsors and Collaborators

University of Minnesota - Clinical and Translational Science Institute

Investigators

Principal Investigator:

Lynda E Polgreen, M.D.

University of Minnesota - Clinical and Translational Science Institute

More Information

No publications provided

Responsible Party:	University of Minnesota ( Lynda Polgreen, M.D. )
Study ID Numbers:	0808M43681
Study First Received:	September 8, 2008
Last Updated:	March 18, 2009
ClinicalTrials.gov Identifier:	NCT00748969 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Minnesota - Clinical and Translational Science Institute:

MPS I
MPS II
MPS VI
growth hormone
short stature

Additional relevant MeSH terms:

Metabolism, Inborn Errors
Mucopolysaccharidoses
Metabolic Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases

Connective Tissue Diseases
Mucinoses
Carbohydrate Metabolism, Inborn Errors
Mucopolysaccharidosis I

ClinicalTrials.gov processed this record on February 08, 2010