Forteo for the Treatment of Unexplained Osteoporosis in Premenopausal Women

NCT ID: NCT00697463

Last Updated: 2018-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-20
• Study Completion Date: 2012-01-03

Brief Summary

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. The investigators hypothesize that teriparatide will significantly increase bone density (BMD) and improve bone structure in premenopausal women with IOP.

Detailed Description

Idiopathic osteoporosis (IOP) is an uncommon disorder in which otherwise healthy young individuals sustain one or more low-trauma fractures. In 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). This is the beginning of 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. There is 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 on findings, the investigators hypothesize that teriparatide will significantly increase BMD and improve microarchitecture in premenopausal women with IOP.

This is an open-label study of carefully characterized premenopausal women with IOP who are participating in a 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, the study 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 another NIH-funded study as controls.

Conditions

Menopause; Fracture; Osteoporosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Women with Idiopathic osteoporosis (IOP)

Each subject will receive 20 micrograms of Teriparatide (PTH 1-34) subcutaneously daily for 18 -24 months

Group Type: EXPERIMENTAL

Teriparatide (PTH 1-34)

Intervention Type: DRUG

20 micrograms subcutaneous injection daily

Interventions

Teriparatide (PTH 1-34)

20 micrograms subcutaneous injection daily

Intervention Type: DRUG

Other Intervention Names

Forteo

Eligibility 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 48 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth Shane

Professor of Medicine, Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elizabeth Shane, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Adi Cohen, MD

Role: STUDY_DIRECTOR

Columbia University

Locations

Creighton University

Omaha, Nebraska, United States

Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAC6871

Identifier Type: -

Identifier Source: org_study_id