We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov Menu

Growth Hormone Therapy in Osteogenesis Imperfecta

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00001305
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : October 6, 2017
Information provided by (Responsible Party):

Study Description
Brief 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)

Condition or disease Intervention/treatment Phase
Osteogenesis Imperfecta Drug: Humatrope Other: Growth hormone Drug: Nutropin Drug: GRH Phase 3

Detailed Description:
Growth deficiency is a cardinal feature of severe Osteogenesis Imperfecta (OI) and a frequent feature of mild to moderate forms of this disease. Despite the prevalence of short stature among people with OI, few studies have examined treatment options for this feature of OI. Recombinant human growth hormone (rGH) is a treatment for growth deficiency which we have investigated. In our initial studies we have found that many OI children are responsive to rGH especially those with type IV OI. The purpose of this protocol is to examine the effect of growth hormone treatment on linear growth of children with types III and IV OI and correlate growth responsiveness with growth hormone-somatomedin axis and histomorphometry parameters of OI bone.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Studies of Growth Deficiency and Growth Hormone Treatment in Children With Osteogenesis Imperfecta Types III and IV
Study Start Date : November 5, 1991
Primary Completion Date : May 19, 2017
Study Completion Date : May 19, 2017

Arms and Interventions

Intervention Details:
    Drug: Humatrope
    Patients receive a subcutaneous injection.
    Other: Growth hormone Drug: Nutropin Drug: GRH

Outcome Measures

Primary Outcome Measures :
  1. Annual growth rate [ Time Frame: 1 yr then annual to full stature ]

Secondary Outcome Measures :
  1. Vertebral Dexa, fracture rate [ Time Frame: 1 yr then annual to full stature ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   3 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 3 and 8 years of age.

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 degrees 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 degrees 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. 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 through that protocol. Tests will be scheduled as required for that protocol; namely, PFTs every 2 years if normal, every year if abnormal.


Patients who develop scoliosis greater than 40 degrees and/or patients who progress to severe basilar invagination during the study will be removed from the study. Failure to comply with the outlined procedures (blood draws, endocrine testing, bone biopsies, and visit schedule) is also a criterion for withdrawal from the protocol.

Patients who become pregnant.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00001305

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Joan C Marini, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
More Information

Additional Information:
Responsible Party: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier: NCT00001305     History of Changes
Other Study ID Numbers: 920034
First Posted: November 4, 1999    Key Record Dates
Last Update Posted: October 6, 2017
Last Verified: May 19, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) ):
Osteogenesis Imperfecta

Additional relevant MeSH terms:
Osteogenesis Imperfecta
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Genetic Diseases, Inborn
Collagen Diseases
Connective Tissue Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs