Parathyroid Hormone (PTH) for Osteoporosis in Postmenopausal Women

Osteoporosis Clinical Trial

Official title:

Evaluation of Factors That Affect Skeletal Responses to PTH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00086619
• Other study ID #: NIAMS-123
• Secondary ID: 1P50AR044855
• Status: Completed
• Phase: Phase 2
• First received: July 7, 2004
• Last updated: September 26, 2013
• Start date: May 2004
• Est. completion date: December 2009

Study information

• Verified date: September 2013
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Parathyroid hormone (PTH) increases bone formation and thereby improves bone density and bone strength in postmenopausal women with osteoporosis. However, prolonged PTH treatment increases bone formation less and less over time. This study will test whether increasing the daily dose of PTH sustains its ability to improve bone formation, and optional sub-studies will test several potential reasons why PTH's effects on bone formation decline over time.

Description:

In women with postmenopausal osteoporosis, PTH increases bone mineral density more than anti-resorptive agents, and its use markedly reduces the incidence of new spine and non-spine fractures. Still, PTH is not a cure for osteoporosis in many patients because PTH-stimulated bone formation declines as PTH therapy continues. Biochemical analyses suggest that bone formation and resorption peak after 6 to 9 months of daily PTH therapy and then decline progressively.

The study will last 18 months. Blood, urine, and bone density tests will occur at screening. At the start of the study, participants will be randomly assigned to one of two PTH dose regimens. Patients will go to Massachusetts General Hospital at Months 0, 3, 6, 9, 12, 15, and 18 for blood and urine collection. In addition, bone density tests by DXA will be performed at Months 0, 6, 12, and 18, and by quantitative CT scans at Months 0 and 18. Approximately 6 weeks after any change in PTH dose, each participant's blood calcium will be checked 4 to 6 hours after that day's PTH injection, and her 24-hour urine calcium excretion will also be checked.

Participants may enroll in optional substudies that will test whether reduced skeletal responses to long-term treatment with PTH are accompanied by changes in its absorption and/or destruction and whether reduced skeletal responses to long-term treatment with PTH are accompanied by parallel reductions in kidney responses to PTH.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 46 Years to 85 Years

Eligibility

Inclusion Criteria:

• Three or more years after menopause

• Bone mineral density T-score < or = -2.0 by dual-energy x-ray absorptiometry (DXA) of vertebrae or femoral neck, or by quantitative computerized tomography (QCT) of vertebral body trabeculae

Exclusion Criteria:

• Cannot walk without assistance

• Significant heart, kidney, liver, or malignant disease

• Current alcohol abuse

• Major psychiatric disorders

• Other current or past disorders known to affect bone

• Use of medications known to affect bone for > 7 days in the past 12 months

• Use of bisphosphonates or fluoride

• Abnormal blood calcium, PTH, 25-hydroxy vitamin D, creatinine, liver function tests, or complete blood count

• Elevated calcium levels in 24-hour urine collection

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteoporosis
• Osteoporosis, Postmenopausal
• Postmenopausal Osteoporosis

Intervention

Drug:
• synthetic hPTH 1-34
Either daily treatment with self-injected hPTH 1-34 or ascending dose treatment at 6-month intervals of hPTH 1-34

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Yu EW, Neer RM, Lee H, Wyland JJ, de la Paz AV, Davis MC, Okazaki M, Finkelstein JS. Time-dependent changes in skeletal response to teriparatide: escalating vs. constant dose teriparatide (PTH 1-34) in osteoporotic women. Bone. 2011 Apr 1;48(4):713-9. doi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Indices of Bone Turnover	Change from month 0 (pre-treatment) baseline serum aminoterminal propeptide of type I collagen (PINP), osteocalcin (OC), and C-terminal telopeptide (CTX), expressed as an area under the curve (AUC). Each marker measurement result was multiplied by the corresponding subject-specific elapsed study time interval using the trapezoidal rule, and these products were summed to generate a subject-specific AUC (months*ng/ml) for the marker.	Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18.	No
Secondary	Change in Bone Mineral Density (BMD)	Percent change in BMD of the spine, femur, radius, and ulna, and subtotal body, calculated as 100*[(final - month 0)/month 0] in subjects who took study therapy for at least 12 months.	baseline and 18 months (12 months in 4 subjects)	No