Forteo for the Treatment of Unexplained Osteoporosis in Premenopausal Women - Full Text View

Sponsor:	Columbia University
Collaborator:	Eli Lilly and Company
Information provided by:	Columbia University
ClinicalTrials.gov Identifier:	NCT00697463

Purpose

Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. Teriparatide [PTH(1-34)], which is FDA approved for treatment of osteoporosis in men and postmenopausal women, works by stimulating bone formation. We hypothesize that teriparatide will significantly increase bone density (BMD) and improve bone structure in premenopausal women with IOP.

Condition	Intervention	Phase
Premenopause Low Bone Density Fracture Osteoporosis	Drug: Teriparatide (PTH 1-34)	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Teriparatide for the Treatment of Idiopathic Osteoporosis in Premenopausal Women

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Fractures Osteoporosis

Drug Information available for: Teriparatide Teriparatide acetate

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:

The primary endpoint will be change in lumbar spine bone density by Dual energy x-ray absorptiometry (DXA) from baseline to 18 months. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To characterize changes in serum and urine biochemical indices of bone turnover and bone biopsy derived measures of resorption and formation versus baseline. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
To compare serum and urine indices of bone resorption and formation between IOP subjects and healthy controls treated with teriparatide. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	27
Study Start Date:	August 2008
Estimated Study Completion Date:	August 2012
Estimated Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Each subject will receive 20 micrograms of teriparatide subcutaneously daily.	Drug: Teriparatide (PTH 1-34) 20 micrograms subcutaneous injection daily for 18 months Other Name: Forteo
Active Comparator: 2 Each subject will receive a daily injection of 20 micrograms subcutaneously.	Drug: Teriparatide (PTH 1-34) Daily injection of 20 micrograms subcutaneously for 4 weeks Other Name: Forteo

Detailed Description:

Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. In our studies of IOP in men, histomorphometric indices of bone formation are depressed, and affected men respond to PTH(1-34) with robust increases in lumbar spine (LS) bone mineral density (BMD). We are now beginning the third year of an R01 (AR4989603) investigating the etiology and pathogenesis, as well as the histomorphometric and bone microarchitectural features of IOP in premenopausal women. We have found evidence of markedly decreased bone formation and microarchitectural deterioration with decreased mechanical competence/strength.

Teriparatide [PTH(1-34)] is an anabolic agent that stimulates bone formation and improves bone microarchitecture. Based upon our findings, we hypothesize that teriparatide will significantly increase BMD and improve microarchitecture in premenopausal women with IOP.

We will test this hypothesis in an open-label study of carefully characterized premenopausal women with IOP who are participating in our NIH-funded study and who have fragility fractures or very low bone density. Participants in the study will receive 18-24 months of teriparatide and the effects on BMD and microstructure, bone mechanical competence, and bone turnover will be assessed. In order to assess whether teriparatide stimulates bone formation to the same extent in women with IOP as it does in normal women, we will compare the short-term changes (2 and 4 weeks) in biochemical markers of bone formation in response to teriparatide between women with IOP and normal women who are participating in our NIH-funded study as controls.

Eligibility

Ages Eligible for Study:	20 Years to 45 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Premenopausal women of all races
Ages 20 to 48
Regular menses (at least 8 periods in the last 12 months).
FSH < 20 mIU/ml during the early follicular phase, to exclude women in the perimenopause.
Fracture subjects: documented low trauma fracture(s) at age >= 18 (e.g., fracture associated with a fall from a standing height or less).
Low BMD subjects: DXA BMD T score less than or equal to 2.5 at the LS, total hip, femoral neck or distal radius, who have not had a fracture
Control subjects: DXA BMD T score greater than or equal to 1.0 at the LS, total hip, femoral neck and distal radius, who have not had a fracture.
All subjects must use appropriate birth control methods to prevent pregnancy for the duration of teriparatide treatment.

Exclusion Criteria:

Secondary Causes of Osteoporosis
Disorders of mineral metabolism: primary or secondary hyperparathyroidism (serum intact PTH > 65 pg/ml), vitamin D deficiency (serum 25OHD < 30 ng/ml), hypercalciuria (>300 mg/g creatinine), Paget's disease, clinical osteomalacia, osteogenesis imperfecta (OI).
Recent pregnancy or lactation (within past year).
Prolonged amenorrhea (> 6 months) during reproductive years (except during pregnancy or lactation).
History of anorexia nervosa.
Malignancy, except cured basal or squamous cell skin carcinoma.
Endocrinopathy: hyperthyroidism (elevated serum thyroxine and/or suppressed TSH), untreated hypothyroidism, Cushing's syndrome, prolactin-secreting pituitary adenoma.
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 or current use of glucocorticoids, anticonvulsants, anticoagulants, diuretics, methotrexate.
Current use of depot preparations of progesterone or GnRH agonists.
Current use of drug therapies for osteoporosis (estrogen preparations other than contraceptives, raloxifene, bisphosphonates, calcitonin, PTH). Subjects who agree to discontinue use of these medications will be eligible to participate 6 months after discontinuing raloxifene or calcitonin, and 12 months after discontinuing bisphosphonates. Total exposure to bisphosphonates must be < 1 year. Subjects who have taken PTH at any time in the past will not be eligible.
Additional contraindications to teriparatide use: Unexplained elevated total or bone specific alkaline phosphatase or prior external beam or implant radiation therapy involving the skeleton.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697463

Locations

United States, New York
Columbia University Medical Center
New York, New York, United States, 10032

Sponsors and Collaborators

Columbia University

Eli Lilly and Company

Investigators

Principal Investigator:	Elizabeth Shane, MD	Columbia University
Study Director:	Adi Cohen, MD	Columbia University

More Information

No publications provided

Responsible Party:	Elizabeth Shane, MD, Columbia University Medical Center
ClinicalTrials.gov Identifier:	NCT00697463 History of Changes
Other Study ID Numbers:	AAAC6871
Study First Received:	June 11, 2008
Last Updated:	June 21, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Columbia University:

Teriparatide
Forteo
Osteopenia
Osteoporosis

Fracture
Low Bone Density
Premenopausal women

Additional relevant MeSH terms:

Fractures, Bone
Osteoporosis
Wounds and Injuries
Bone Diseases, Metabolic
Bone Diseases

Musculoskeletal Diseases
Teriparatide
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012