Cyclic Versus Daily Teriparatide on Bone Mass

NCT00668941 | Unknown Phase 2

• 2 other identifiers: R01 AR056651-01A2, 5RO1 ARO5R01AR056651-01A2
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Osteoporosis is a disease that affects millions of individuals in the United States and abroad. It leads to decreased bone mass and causes an increased risk of fracture. This study will compare continuous versus cyclic treatment with teriparatide combined with alendronate, another drug for osteoporosis, or teriparatide alone in women with osteoporosis.

Conditions

Osteoporosis

Keywords

Bone Density; Bone Turnover; Histomorphometry

Outcome Measures

Primary Outcomes (1)

• Bone density

  24 and 48 months

Secondary Outcomes (2)

• Histomorphometry of iliac crest bone biopsies

  Measured at Week 7 and Month 7

• HRpQCT (tibia, radius) and QCT (spine and hip)and FEA of these QCT scans

  48 months

Study Arms (6)

1

EXPERIMENTAL

Participants in this group will have been treated with alendronate for at least 1 year prior to study entry. Upon study entry, they will receive a continuous regimen of daily teriparatide (20 mcg subcutaneously) for 48 months, in addition to alendronate. Biopsies will be performed at Week 7 or Month 7.5. The participants will then have the option to be followed while taking alendronate alone for 24-48 months.

Drug: Teriparatide; Drug: Alendronate; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D3

2

EXPERIMENTAL

Participants in this group will have been treated with alendronate for at least 1 year prior to study entry. Upon study entry, they will receive a cyclical regimen of teriparatide, in addition to alendronate. Teriparatide will be administered subcutaneously in 20-mcg doses daily for 3 months. They will receive no teriparatide for the following 3 months, and then teriparatide treatment will continue for the 3 months after that. This schedule will continue for 24 months with an aption to all participants to continue cyclic teriparatide for another 24 months. Biopsies will be performed at Week 7 or Month 7.5.

Drug: Teriparatide; Drug: Alendronate; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D3

3

ACTIVE COMPARATOR

Participants in this group will have been treated with alendronate for at least 1 year prior to study entry. Upon study entry, they will continue taking alendronate alone. Biopsies will be performed at Week 7 and then participants in this group will be offered teriparatide as part of Group 2 or 3.

Drug: Alendronate; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D3

4

EXPERIMENTAL

Participants in this group will receive a continuous regimen of teriparatide (20 mcg delivered subcutaneously) daily for 48 months. Biopsies will be performed at Week 7 or Month 7.5. At 24 months the participants will then have the option of taking alendronate and remaining in the study for another 24 months.

Drug: Teriparatide; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D3

5

EXPERIMENTAL

Participants in this group will receive a cyclical regimen of teriparatide. Teriparatide will be administered subcutaneously in 20-mcg doses daily for 3 months. They will receive no teriparatide for the following 3 months, and then teriparatide treatment will continue for the 3 months after that. This schedule will continue for 24 months with an option to all participants to continue cyclic teriparatide for another 24 months. Biopsies will be performed at Week 7 or Month 7.5.

Drug: Teriparatide; Dietary Supplement: Calcium; Dietary Supplement: Vitamin D3

6

ACTIVE COMPARATOR

Participants in this group will take only calcium and vitamin D supplements. Biopsies will be performed at Week 7. Participants will then be offered the standard care for osteoporosis or they may enter the study in Group 4 or 5.

Dietary Supplement: Calcium; Dietary Supplement: Vitamin D3

Interventions

Teriparatide DRUG

Teriparatide will be given subcutaneously in 20-mcg doses either continuously or cyclically.

1; 2; 4; 5

Alendronate DRUG

Participants will take 70 mg per week of alendronate for 48 months.

1; 2; 3

Calcium DIETARY_SUPPLEMENT

Calcium supplements will be administered in varied amounts for all participants, but each participant will take enough to bring her total daily calcium intake to 1,200 mg.

1; 2; 3; 4; 5; 6

Vitamin D3 DIETARY_SUPPLEMENT

Vitamin D3 supplements will be administered in varied amounts for all participants, but each participant will take enough to bring her total daily intake to 1,200 mg.

1; 2; 3; 4; 5; 6

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of osteoporosis or T score below -2 plus one or more osteoporosis related fractures
• Two measurable vertebrae between L1 and L4
• Willing to undergo a single iliac crest biopsy after administration of 4 tetracycline labels

You may not qualify if:

• Secondary causes of osteoporosis or presence of a skeletal disorder other than osteoporosis
• Uses drugs likely to affect skeletal or calcium homeostasis
• Multiple vertebral fractures or severe degenerative changes with fewer than two evaluable vertebrae
• Unwilling to undergo a single iliac crest biopsy
• History of allergy to tetracyclines, exposure to tetracyclines within the last year, or any remote long term use of tetracyclines
• Current use of anti-resorptive medicines (other than alendronate for half the female participants)
• Use of hormone therapy, estrogen therapy, raloxifene, or calcitonin within 6 months before study entry
• Use of any bisphosphonate for more than 3 months within 2 years before study entry (only applies to participants in Groups 4, 5, and 6)
• History of a kidney stone within 5 years before study entry or any history of multiple kidney stones
• Hypercalcemia, hypercalciuria, or elevated parathyroid hormone (reduced 25-hydroxyvitamin D will be corrected prior to admission)
• Esophageal ulceration or stricture or known hypersensitivity to bisphosphonates
• History of external radiation therapy
• Unlikely or unable to complete the study, as determined by the investigators
• Illicit drug use or excessive alcohol consumption

Sponsors & Collaborators

• Helen Hayes Hospital: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• Health Research, Inc.: collaborator

Study Sites (1)

Helen Hayes Hospital

West Haverstraw, New York, 10993, United States

Location

Related Publications (2)

• Ganapathy A, Nieves JW, Keaveny TM, Cosman F. Effects of four-year cyclic versus two-year daily teriparatide treatment on volumetric bone density and bone strength in postmenopausal women with osteoporosis. Bone. 2023 Feb;167:116618. doi: 10.1016/j.bone.2022.116618. Epub 2022 Nov 21.

  PMID: 36410666 DERIVED

• Cosman F, Nieves JW, Roimisher C, Neubort S, McMahon DJ, Dempster DW, Lindsay R. Administration of teriparatide for four years cyclically compared to two years daily in treatment Naive and alendronate treated women. Bone. 2019 Mar;120:246-253. doi: 10.1016/j.bone.2018.10.020. Epub 2018 Oct 21.

  PMID: 30355512 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

Teriparatide; Alendronate; Calcium; Cholecalciferol

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Robert Lindsay, MD, PhD

  Helen Hayes Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Study Record Dates

• First Submitted: April 27, 2008
• First Posted: April 29, 2008
• Study Start: September 1, 2005
• Primary Completion: February 1, 2016
• Study Completion: November 1, 2017
• Last Updated: August 10, 2017

Record last verified: 2017-08

Locations

US (1)