Osteogenesis Imperfecta
Conditions
Keywords
Osteogenesis Imperfecta, Brittle Bone Disease, Fragility Fractures
Brief summary
The purpose of this study is to determine the effectiveness of teriparatide (FORTEO), which is human parathyroid hormone 1-34, for increasing bone mass and improving bone structure in adults affected with Osteogenesis Imperfecta (OI).
Detailed description
The purpose of this study is to determine the effectiveness of teriparatide (FORTEO), which is human parathyroid hormone 1-34, for increasing bone mass and improving bone structure in adults affected with Osteogenesis Imperfecta (OI). Osteogenesis imperfecta is an inherited disorder of type I collagen, a major component of bones, and is characterized by multiple fractures and deformities. OI affects approximately 1-2 of every 10,000 individuals. Virtually all of the studies of potential treatments for OI have evaluated the effects of medications only on children with OI. There is no cure for osteogenesis imperfecta and there is no established medical therapy for adults with the disorder. There are very limited data concerning the usefulness of parathyroid hormone therapy in OI. An effective anabolic therapy for the treatment of adult patients with OI could be a valuable asset to the affected patients. In this study, the working hypothesis is that individuals affected with OI who are treated with Forteo will experience increased spine and hip bone mineral density and an increase in bone strength. Although Forteo is not expected to change the defect in the collagen produced, but is postulated to increase the quantity of bone formed and improve bone strength. This will be a placebo controlled, double blinded trial; half the patients will receive Forteo 20 ug/day SQ. Adult patients (age at least 18 yrs) with OI will be enrolled for a treatment duration of 18 months. Blood, urine, and bone density/strength tests will be done during the study to assess efficacy and safety.
Interventions
Teriparatide (FORTEO) 20mcg, subcutaneous injection, once daily
DRUGPlacebos
Sponsors
Eli Lilly and Company
Osteogenesis Imperfecta Foundation
National Institutes of Health (NIH)
National Center for Research Resources (NCRR)
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Previous established diagnosis of Osteogenesis Imperfecta AND * \> 2 previous adult fractures, AND/OR * BMD at lumbar spine, femoral neck or total hip T score \< -2.0
Exclusion criteria
* Open epiphyses. * History of external beam radiation to the skeleton. * Pagets disease. * Bone metastases or skeletal malignancies. * Total lifetime exposure to any antiresorptive medication \< 90 days (Primary Inclusion). * Treatment with any antiresorptive medication 12 months proceeding enrollment - (Secondary Inclusion). * Women with OI who are pregnant or unwilling to use 1 form of contraception. * Vitamin D insufficiency (25-hydroxyvitamin D \<15ng/ml)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spine Bone Mineral Density (BMD) | baseline and 18 months | bone density by dual energy xray absorptiometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Hip BMD | baseline and 18 months | bone density by dual energy xray absorptiometry |
Countries
United States
Participant flow
Pre-assignment details
One participant was formally enrolled but then dropped out before the first study treatment was administered.
Participants by arm
| Arm | Count |
|---|---|
| Teriparatide (FORTEO) Once daily SQ administration of Teriparatide (FORTEO) 20 ug for 18 months
Teriparatide (FORTEO): Teriparatide (FORTEO) 20mcg, subcutaneous injection, once daily | 38 |
| Placebo Daily SQ placebo for 18 months
Placebos | 40 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | scan not analyzable | 3 | 6 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Teriparatide (FORTEO) | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 40.8 years STANDARD_DEVIATION 12.9 | 41.2 years STANDARD_DEVIATION 10.1 | 41 years STANDARD_DEVIATION 11.5 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 22 Participants | 24 Participants | 46 Participants |
| Sex: Female, Male Male | 16 Participants | 16 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 1 / 40 |
| other Total, other adverse events | 0 / 38 | 0 / 40 |
| serious Total, serious adverse events | 0 / 38 | 0 / 40 |
Outcome results
Primary
Spine Bone Mineral Density (BMD)
bone density by dual energy xray absorptiometry
Time frame: baseline and 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide (FORTEO) | Spine Bone Mineral Density (BMD) | 6.1 percentage of change in g/cm2 | Standard Error 1.5 |
| Placebo | Spine Bone Mineral Density (BMD) | 2.8 percentage of change in g/cm2 | Standard Error 1.3 |
Secondary
Total Hip BMD
bone density by dual energy xray absorptiometry
Time frame: baseline and 18 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriparatide (FORTEO) | Total Hip BMD | 2.6 percentage of change in g/cm2 | Standard Error 2 |
| Placebo | Total Hip BMD | -2.4 percentage of change in g/cm2 | Standard Error 1.8 |