Protocol Number: 92-CH-0034

Title:

Growth Hormone Therapy in Osteogenesis Imperfecta

Number:

92-CH-0034

Summary:

Growth deficiency is a key feature of severe Osteogenesis Imperfecta (OI) and a frequent feature of mild to moderate forms of the disease. The reason that children with OI are short is not fully understood. We do know that details such as the number of fractures suffered or the type of OI do not fully explain the short stature of OI. Growth patterns have been defined for children with OI Types I, III, and IV. At about 12 months of age, children with Types III and IV OI demonstrate a predictable plateau of their linear growth rate. Type IV OI children begin to resume a normal growth rate at about age four to five years, but they will not "catch up" to a normal height, as they have "lost" a significant period of growth. The plateau usually continues for children with Type III OI. The reason for this growth plateau is unknown. There have been no studies which evaluate the growth of OI children in this age range. Our previous studies of growth in OI children have begun at age 5 years.

We have studied growth in OI children for the past 10 years. Different medications have been tried to both stimulate growth and improve bone density. Some children have responded to growth hormone (their growth rate increased by at least 50%) and some did not. The majority of children who did respond were Type IV. However, we need to carefully treat and study more children to try to determine which children will benefit from growth hormone medication.

The Goals of this Study Are:

1. We want to try to find a cause for the growth plateau common in types III and IV OI. Long-term, our goal is to develop a treatment to eliminate this plateau.

2. We want to see how long and how well OI bone will respond to growth stimulation.

3. We hope to find a "predictor" for who will respond to growth hormone and who will not, by measuring your child's endocrine and growth hormone function before receiving any growth hormone treatment.

4. We want to measure the effects of growth stimulation on bone density, and the quality of OI bone.

5. We want to see if there are long term benefits resulting from this treatment in the form of final adult height, trunk height, and possibly improved function of the respiratory system.

Median Subject Age (on p. 1 of webpage): 1-15 years (replaces 0-20)

Sponsoring Institute:

National Institute of Child Health and Human Development (NICHD)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA

Patients will be recruited with the goal of including at least 10 each of individuals with clinical/biochemical criteria of types III and IV OI who are between 1 and 8 years of age. Patients will be stratified by age; those younger than 4 years of age will enter the study of the growth plateau, and those who have begun to grow again will enter the study of growth hormone treatment in OI.

Height: Individuals with type III OI have severe short stature by definition; individuals with type IV OI recruited to the study will have height less than the 3rd percentile for age. All individuals will be required to furnish growth records, especially height and head circumference, from at least the preceding two years.

Long bone status: Participants must have radiographic evidence that long bone epiphyses have not yet fused. In addition, 60 or greater angulation of a femur will exclude a child, pending surgical management or medical clearance.

Spine: Prospective participants will be evaluated for scoliosis and spinal compressions. Participants with scoliosis greater than 40 will be excluded unless evidence is presented that the scoliosis has been stable for the prior two years. Participants with corrective rods in their spine will be excluded.

Neuro status: All patients will be co-enrolled in 97-CH-0064, and will be screened for Basilar Invagination through that protocol. Children who are initially screened by spiral CT scan with MRI confirmation and determined to have severe BI will be excluded from participation in this study. Severe BI is defined by NIH data as distortion of the angle between the pons and medulla and or compression of posterior fossa contents.13 We are only beginning to define the parameters of BI in this population, and we do not know why some children with BI progress in severity and some do not. Until those questions are answered, we feel it would not be prudent to stimulate growth in a child we know to have a severe form of BI at enrollment. Pulmonary status: All children will be co-enrolled in 97-CH-0064, and will have pulmonary function testing and polysomnograms through that protocol. Tests will be scheduled as required for that protocol; namely, PFTs every 2 years if normal, every year if abnormal, and polysomnograms every 4 years if normal, and every 2 years if abnormal. 6. Potential participants who have not participated in the growth plateau study will still be eligible for participation in the growth hormone treatment trial. These patients, if entering from outside the protocol, must be between age 4 and 8 years, and must have documented growth records that demonstrate that they have emerged from the growth plateau. The first year in the protocol for these patients will be the pretreatment year, in which they will not receive growth hormone but will come to NIH on the schedule for the pretreatment visits. Children older than 8 years of age are not eligible for this protocol, in order to maximize the potential benefits of the growth stimulation by beginning treatment as early as possible.

Special Instructions: Currently Not Provided

Keywords:

Heparin Lock

Bone Biopsy

Children

Collaborative Study

Osteogenesis Imperfecta

Growth Hormone

Short Stature

Bone Density

Recruitment Keywords:

None

Conditions:

Dwarfism

Osteogenesis Imperfecta

Investigational Drug(s):

Humatrope

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

The growthhormone and somatomedin axis in short children with osteogenesis imperfecta

Heritable diseases of collagen

Overnight growth hormone concentrations are usually normal in pubertal children with idiopathic short stature-a clinical research center study

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