Parathyroid Hormone (PTH) for Osteoporosis in Postmenopausal Women

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Robert M. Neer, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00086619
First received: July 7, 2004
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Postmenopausal Osteoporosis
Osteoporosis
Drug: synthetic hPTH 1-34
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Factors That Affect Skeletal Responses to PTH

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Changes in Indices of Bone Turnover [ Time Frame: Each index of bone turnover was measured at study month 0, 1.5, 3, 6, 7.5, 9, 12, 13.5, 15, and 18. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Bone Mineral Density (BMD) [ Time Frame: baseline and 18 months (12 months in 4 subjects) ] [ Designated as safety issue: No ]
    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.


Enrollment: 80
Study Start Date: May 2004
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: constant dose
Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a constant dose of 30 mcg/day.
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
Other Name: synthetic human parathyroid hormone 1-34
Experimental: ascending dose
Participants will receive synthetic human parathyroid hormone fragment 1-34 (hPTH 1-34) once-daily in a dose that ascends at 6 month intervals (20-30-40 mcg/day).
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
Other Name: synthetic human parathyroid hormone 1-34

Detailed 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.

  Eligibility

Ages Eligible for Study:   46 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086619

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Robert M. Neer, MD Massachusetts General Hospital
Principal Investigator: Joel S. Finkelstein, MD Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Robert M. Neer, MD, Associate Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00086619     History of Changes
Other Study ID Numbers: NIAMS-123, 1P50AR044855
Study First Received: July 7, 2004
Results First Received: June 7, 2012
Last Updated: September 26, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Osteoporosis
Parathyroid hormone
Teriparatide
Bone formation
Bone resorption

Additional relevant MeSH terms:
Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014