Clinical Trial of Growth Hormone in MPS I, II, and VI

• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00748969
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Duration (Months): 58
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI	Drug: Somatropin (DNA origin)	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Growth hormone treatmen Growth hormone treatment arm. Somatropin (DNA origin)	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.; Other Names: Nutropin AQ
No Intervention: No growth hormone treatment in year 1 No growth hormone treatment in year 1; option for treatment in year 2 open-label period.

Outcome Measures

Primary Outcome Measures

1. Change in Growth Velocity From Baseline to End of Study Year 1. [12 months]

Secondary Outcome Measures

1. Safety: Number Drug Related SAEs [1 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Investigators

• Principal Investigator: Lynda E Polgreen, M.D., University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• ClinicalTrials.gov Identifier: NCT00748969
• Other Study ID Numbers: 0808M43681
• First Posted: Sep 9, 2008
• Last Update Posted: Sep 5, 2018
• Last Verified: Nov 1, 2014

• Keywords provided by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: MPS I; MPS II; MPS VI; growth hormone; short stature
• Additional relevant MeSH terms: Mucopolysaccharidosis II; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis VI

Study Results

Participant Flow

Arm/Group Title	Growth Hormone Treatmen	No Growth Hormone Treatment in Year 1
Arm/Group Description	Growth hormone treatment arm. Somatropin (DNA origin) 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.	No growth hormone treatment in year 1; option for treatment in year 2 open-label period.
Period Title: Overall Study
STARTED	1	1
COMPLETED	0	0
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Growth Hormone Treatmen	No Growth Hormone Treatment in Year 1	Total
Arm/Group Description	Growth hormone treatment arm. Somatropin (DNA origin) 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.	No growth hormone treatment in year 1; option for treatment in year 2 open-label period.	Total of all reporting groups
Overall Participants	1	1	2
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	10.9	13.5	12.2
Age (Count of Participants)
<=18 years	1 100%	1 100%	2 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	1 100%	1 100%	2 100%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%

Outcome Measures

1. Primary Outcome

Title	Change in Growth Velocity From Baseline to End of Study Year 1.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Zero participants analyzed in the "No growth hormone treatment" group due to subject withdrew from study as soon as informed they were assigned the no treatment group.

Arm/Group Title	Growth Hormone Treatment	No Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment arm. Somatropin (DNA origin) 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.	Observation only: no growth hormone treatment and no placebo.
Measure Participants	1	0
Number [cm/yr]	NA

2. Secondary Outcome

Title	Safety: Number Drug Related SAEs
Time Frame	1 months

Outcome Measure Data

Analysis Population Description

Study stopped early due to inability to enroll participants.

Arm/Group Title	Growth Hormone Treatment	No Growth Hormone Treatment
Arm/Group Description	Growth hormone treatment arm. Somatropin (DNA origin) 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.	Observation only: no growth hormone treatment and no placebo.
Measure Participants	1	0
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	Zero participants analyzed in the "No growth hormone treatment" group due to subject withdrew from study as soon as informed they were assigned the no treatment group.
Arm/Group Title	GH Treatment		No GH Treatment
Arm/Group Description	Growth hormone treatment arm. Somatropin (DNA origin) 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.		No placebo/no treatment
All Cause Mortality
	GH Treatment		No GH Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	GH Treatment		No GH Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	GH Treatment		No GH Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/0 (NaN)
Nervous system disorders
Headache	1/1 (100%)	1	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
worsening OSA	1/1 (100%)	1	0/0 (NaN)	0

Limitations/Caveats

[Not Specified]

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.