Growth Hormone Therapy in Osteogenesis Imperfecta

NCT00001305 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 92003492-CH-0034
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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. 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. 2.We want to see how long and how well OI bone will respond to growth stimulation.
3. 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. 4.We want to measure the effects of growth stimulation on bone density, and the quality of OI bone.
5. 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.

Conditions

Osteogenesis Imperfecta

Keywords

Osteogenesis Imperfecta

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects Who Met Criteria of Increase in Growth Rate Since Baseline.

  The proportion of subjects who met the study criteria of at least 50% increase in growth rate since baseline.

  1 year

Study Arms (1)

Growth Hormone

EXPERIMENTAL

Treatment of children with types III and IV osteogenesis imperfecta with Humatrope

Drug: Humatrope

Interventions

Humatrope DRUG

Patients receive a subcutaneous injection.

Growth Hormone

Eligibility Criteria

• Age: 3 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Marini JC, Bordenick S, Heavner G, Rose S, Hintz R, Rosenfeld R, Chrousos GP. The growth hormone and somatomedin axis in short children with osteogenesis imperfecta. J Clin Endocrinol Metab. 1993 Jan;76(1):251-6. doi: 10.1210/jcem.76.1.8421094.

  PMID: 8421094 BACKGROUND

• Prockop DJ, Kivirikko KI. Heritable diseases of collagen. N Engl J Med. 1984 Aug 9;311(6):376-86. doi: 10.1056/NEJM198408093110606. No abstract available.

  PMID: 6146097 BACKGROUND

• Rose SR, Municchi G, Barnes KM, Cutler GB Jr. Overnight growth hormone concentrations are usually normal in pubertal children with idiopathic short stature--a Clinical Research Center study. J Clin Endocrinol Metab. 1996 Mar;81(3):1063-8. doi: 10.1210/jcem.81.3.8772577.

  PMID: 8772577 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Osteogenesis Imperfecta

Interventions

Human Growth Hormone

Condition Hierarchy (Ancestors)

Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Marini, Joan
• Organization: National Institute of Child Health and Human Development

marinij@mail.nih.gov

+1 301 594 3418

Study Officials

• Joan C Marini, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: November 5, 1991
• Primary Completion: May 19, 2017
• Study Completion: May 19, 2017
• Last Updated: January 29, 2019
• Results First Posted: January 29, 2019

Record last verified: 2017-05-19

Locations

US (1)