Forteo Trial on Idiopathic Osteoporosis in Premenopausal Women
|Information provided by (Responsible Party):||Elizabeth Shane, Columbia University|
Idiopathic osteoporosis (IOP) is defined as osteoporosis that affects young, otherwise completely healthy individuals with no secondary cause of bone loss. In the course of our prior research with premenopausal women with IOP, the investigators have shown that women with IOP have low areal bone mineral density (aBMD) at the spine, hip and forearm compared to normal women. Additionally, using noninvasive high resolution imaging of the central and peripheral skeleton and detailed analyses of transiliac crest bone biopsies, the investigators identified several features of bone quality in premenopausal women with IOP.
There is currently no FDAapproved therapy for IOP in premenopausal women. However, teriparatide (Forteo) has been shown to improve bone mass and microarchitecture in postmenopausal women and is approved for men with primary or idiopathic osteoporosis, as well as men, premenopausal and postmenopausal women with glucocorticoid-induced osteoporosis. Because IOP in premenopausal women is an orphan disease, with an estimated prevalence of about 113,000 in the United States, pharmaceutical companies are unlikely to support development of therapies for this indication. Therefore the major objective of this protocol is to establish the safety and efficacy of teriparatide in premenopausal women with IOP in a phase 2 clinical trial. All subjects will receive teriparatide as part of the study, but a randomly selected group of patients (10) will receive one year of placebo injections first before starting their two years of treatment. The remainder of subjects (30) will receive active drug only for two years.
|Adult Idiopathic Generalized Osteoporosis||Drug: Teriparatide
Drug: Saline Placebo
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Randomized Controlled Trial of Teriparatide for the Treatment of Idiopathic Osteoporosis in Premenopausal Women|
- Change in lumbar spine bone mineral density (LS-BMD) [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2012|
|Estimated Study Completion Date:||November 2016|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
|Active Comparator: Teriparatide (Forteo)
Daily injection of Teriparatide for treatment of idiopathic osteoporosis
Daily injection of 20 mcg teriparatide for the treatment of idiopathic osteoporosis for 24 months.
Other Name: Forteo
|Placebo Comparator: Placebo saline injection
Daily injection of saline placebo for 12 months, followed by 24 months of teriparatide treatment for idiopathic osteoporosis.
|Drug: Saline Placebo
Daily injection of saline placebo for 12 months, followed by teriparatide treatment for 24 months.
|Ages Eligible for Study:||20 Years to 45 Years|
|Genders Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- Premenopausal women, aged 20-45, with regular menses and no historical or biochemical secondary cause of osteoporosis; the lower age limit is to ensure epiphyses are fused, the upper to make it less likely that women will enter menopause during the study. All subjects under age 25 will be screened prior to drug administration to rule out open epiphyseal plates.
- Documented adult fractures judged to be low-trauma (trauma equivalent to a fall from a standing height or less) and/or T < -2.5 or Z score <-2.0 at the LS, FN or TH. Inclusion criteria vary slightly based on age category:
- Premenopausal women ages 20-35 years must have at least one major osteoporotic fracture (excluding fractures of fingers, toes and face) AND low BMD defined as a T-score or Z-score greater than or equal to -1.5.
- Premenopausal women above the age of 35 years should have a history of fracture AND/OR low BMD defined as Z-score < -2.0. Women above age 35 may also be enrolled on the basis on low BMD alone, without presence of prior low trauma fracture.
- Must be willing to use effective contraception throughout the period of study drug administration
- History of any condition that increases the risk of osteosarcoma (Paget's disease, skeletal irradiation)
- Early follicular phase serum FSH>20 mIU/ml (to exclude perimenopausal women)
- Disorders of mineral metabolism: 1o/2 o hyperparathyroidism, osteomalacia, osteogenesis imperfecta (OI) or Ehlers Danlos (ED). Subjects will not routinely undergo genetic testing for OI or ED as part of their screening evaluation. However, each subject will have a detailed medical and family history and a complete physical examination by one of the physician investigators. Women with historical features or physical examination findings suggestive of OI or ED will be referred for genetic evaluation. If the genetic evaluation is positive for OI or ED, the subject will be excluded from participation.
- Vitamin D deficiency (serum 25-OHD<20 ng/ml). Women with levels of 20-30 ng/ml will be eligible after treatment with vitamin D has resulted in levels >30 ng/ml.
- Pregnancy or lactation within past 12 months
- Prolonged amenorrhea (> 6 months) during reproductive years (except pregnancy or lactation)
- History of an eating disorder (anorexia nervosa, bulimia)
- Malignancy, except cured basal or squamous cell skin carcinoma
- Endocrinopathy: new onset untreated hyperthyroidism, hypothyroidism, Cushing's syndrome, prolactinoma
- Renal insufficiency (serum creatinine above upper limit of female normal range)
- Liver disease (AST, ALT, bilirubin, total alkaline phosphatase activity above upper normal limit)
- Intestinal disorders (celiac disease, pancreatic insufficiency, inflammatory bowel disease)
- History/current GCs, anticonvulsants, anticoagulants, methotrexate, depot progesterone, GnRH agonists
- Drugs for osteoporosis (raloxifene, bisphosphonates, denosumab, calcitonin, TPTD). Subjects who discontinue these medications will be eligible 3 months after stopping raloxifene or calcitonin, 12 months after stopping alendronate, risedronate, ibandronate, or pamidronate and 18 months after stopping denosumab or zoledronate. Total bisphosphonate exposure must be < 1 year. Subjects who have taken TPTD or zoledronate in the past will not be eligible.