NCT00005901

Brief Summary

This study will evaluate the effect of pamidronate a drug that decreases bone resorption (breakdown) on osteogenesis imperfecta. This is a genetic disorder of collagen, the major protein in bone. The abnormal collagen causes weak bones, and children with severe osteogenesis imperfecta sustain many fractures throughout their lives. They also have growth deficiency, curvature of the spine, crumbling teeth, hearing loss, easy bruising and heart and lung problems. The study will compare bone density, quality and strength, final adult height, trunk height, and functional ability in children who receive 1) pamidronate every 3 months, 2) pamidronate every 3 months + growth hormone injections, 3) pamidronate every 6 months, or 4) pamidronate every 6 months + growth hormone injections. Children 2 years of age and older with severe osteogenesis imperfecta (types III and IV) may be eligible for this study. Those enrolled will be randomly assigned to groups according to age; children two to four years of age will be randomly assigned to receive pamidronate every 3 or every 6 months. Children four years of age and older may participate in the growth hormone treatment groups. These children will continue on growth hormone until they reach their adult height or fail to grow as much as would be expected for someone on growth hormone. Patients will be followed in the clinic every 3 months for a history, physical examination, X-rays, blood tests, and measurements (weight, head circumference, and bone lengths). Children will receive a 3 to 4 hour infusion of pamidronate through an intravenous catheter (thin flexible tube placed in a vein) once a day for 3 days each visit. (Once inserted, the catheter is left in place to avoid multiple needle sticks for administering the drug and collecting blood samples.) Children who are taking growth hormone will be given the drug at the first treatment visit. At that time, the accompanying parent will be instructed on how to mix the drug and give injections. The child receives an injection 6 days a week (Sunday off).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jun 2000

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2000

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

June 6, 2000

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 7, 2000

Completed
13.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
1 year until next milestone

Results Posted

Study results publicly available

March 1, 2016

Completed
Last Updated

March 1, 2016

Status Verified

February 1, 2016

Enrollment Period

13.9 years

First QC Date

June 6, 2000

Results QC Date

November 24, 2015

Last Update Submit

February 1, 2016

Conditions

Osteogenesis Imperfecta

Keywords

BisphosphonatesGrowth HormoneBone DensityOsteogenesis Imperfecta

Outcome Measures

Primary Outcomes (6)

  • Change in Bone Mineral Density in Response to Pamidronate

    Dual-energy X-ray Absorptiometry (DXA) measurements were obtained using a Hologic QDR 4500 densitometer and low density software package. Measurements have a precision of 0.011 SD. Raw measurements were converted to Z-scores for analysis using the manufacturer's reference standards for age and pubertal status.

    Baseline vs. 12 months after first dose

  • Change in Bone Mineral Density in Response to Pamidronate

    Dual-energy X-ray Absorptiometry (DXA) measurements were obtained using a Hologic QDR 4500 densitometer and low density software package. Measurements have a precision of 0.011 SD. Raw measurements were converted to Z-scores for analysis using the manufacturer's reference standards for age and pubertal status.

    Baseline vs. 18 months after first dose

  • Change in Bone Mineral Density in Response to Pamidronate

    Dual-energy X-ray Absorptiometry (DXA) measurements were obtained using a Hologic QDR 4500 densitometer and low density software package. Measurements have a precision of 0.011 SD. Raw measurements were converted to Z-scores for analysis using the manufacturer's reference standards for age and pubertal status.

    Baseline vs. 24 months after first dose

  • Change in Bone Mineral Density in Response to Pamidronate

    Dual-energy X-ray Absorptiometry (DXA) measurements were obtained using a Hologic QDR 4500 densitometer and low density software package. Measurements have a precision of 0.011 SD. Raw measurements were converted to Z-scores for analysis using the manufacturer's reference standards for age and pubertal status.

    Baseline vs. 30 months after first dose

  • Change in Bone Mineral Density in Response to Pamidronate

    Dual-energy X-ray Absorptiometry (DXA) measurements were obtained using a Hologic QDR 4500 densitometer and low density software package. Measurements have a precision of 0.011 SD. Raw measurements were converted to Z-scores for analysis using the manufacturer's reference standards for age and pubertal status.

    Baseline vs. 36 months after first dose

  • Change in Bone Mineral Density in Response to Pamidronate

    Dual-energy X-ray Absorptiometry (DXA) measurements were obtained using a Hologic QDR 4500 densitometer and low density software package. Measurements have a precision of 0.011 SD. Raw measurements were converted to Z-scores for analysis using the manufacturer's reference standards for age and pubertal status.

    Baseline vs. 6 months after first dose

Study Arms (2)

Pamidronate every 3 months for 3 years

ACTIVE COMPARATOR

Subjects who received Pamidronate every 3 months for 3 years.

Drug: Pamidronate (Aredia)

Pamidronate every 6 months for 3 years

ACTIVE COMPARATOR

Subjects who received Pamidronate every 6 months for 3 years.

Drug: Pamidronate (Aredia)

Interventions

Pamidronate (Aredia)DRUG

Patients receive a dose of 1mg/kg/cycle (3-day infusion = 1 cycle)

Pamidronate every 3 months for 3 yearsPamidronate every 6 months for 3 years

Eligibility Criteria

AgeUp to 16 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Children enrolled in this study will be limited to those with Sillence types III and IV OI, as determined by clinical and genetic criteria.
  • Most of the children who will be included in this study are already enrolled in the protocols Evaluation and Intervention for Ambulation, Growth, and Basilar Invagination in Osteogenesis Imperfecta (97-CH-0064) and Growth Hormone Therapy in Osteogenesis Imperfecta (92-CH-0034).
  • Patients are excluded from protocol 92-CH-0034 if they have scoliosis of greater than 40 degrees unless scoliosis has been stable over the past two years, or evidence of severe basilar invagination.
  • Patients with previous exposure to bisphosphonates in outside trials will be considered for participation in this trial.

You may not qualify if:

  • Pregnancy.
  • Patients that have had or will have surgery to place instrumentation in the spine (i.e. result of spine fusion).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

  • Marini JC. Osteogenesis imperfecta: comprehensive management. Adv Pediatr. 1988;35:391-426. No abstract available.

    PMID: 3055864BACKGROUND

  • 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: 6146097BACKGROUND

  • Marini JC, Bordenick S, Heavner G, Rose S, Chrousos GP. Evaluation of growth hormone axis and responsiveness to growth stimulation of short children with osteogenesis imperfecta. Am J Med Genet. 1993 Jan 15;45(2):261-4. doi: 10.1002/ajmg.1320450223.

    PMID: 8456815BACKGROUND

Related Links

MeSH Terms

Conditions

Osteogenesis Imperfecta

Interventions

Pamidronate

Condition Hierarchy (Ancestors)

OsteochondrodysplasiasBone Diseases, DevelopmentalBone DiseasesMusculoskeletal DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesCollagen DiseasesConnective Tissue DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

DiphosphonatesOrganophosphonatesOrganophosphorus CompoundsOrganic Chemicals

Results Point of Contact

Title
Joan Marini
Organization
National Institute of Child Health and Human Development
marinij@cc1.nichd.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
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 6, 2000

First Posted

June 7, 2000

Study Start

June 1, 2000

Primary Completion

May 1, 2014

Study Completion

March 1, 2015

Last Updated

March 1, 2016

Results First Posted

March 1, 2016

Record last verified: 2016-02

Locations

US(1)