Cyclic Versus Daily Teriparatide on Bone Mass

NCT ID: NCT00668941

Last Updated: 2017-08-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-09-30

Study Completion Date

2017-11-30

Brief Summary

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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.

Detailed Description

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Osteoporosis is a serious bone disease that has become an important public health problem. It causes significant loss of bone mass and increases the risk of both fracture and architectural problems with the skeleton. Until recently, the treatments available for osteoporosis primarily prevented further deterioration of bone by reducing the rate of remodeling within the skeleton. This can reduce the risk of fracture by approximately 50%. Teriparatide is a new type of drug for people with osteoporosis who are at high risk of fracture. Teriparatide stimulates bone remodeling and can correct the underlying architectural and bone mass abnormalities that are characteristic of osteoporosis. This study will compare continuous versus cyclic treatment with teriparatide combined with alendronate, another drug for osteoporosis, or teriparatide alone in women with osteoporosis.

All participants have completed a parent study of two years that included a screening visit with a physical exam, blood draw, x-rays, EKG, and distribution of calcium and vitamin D supplements. Participants will be separated into two groups according to the treatment they have undergone over the year prior to study entry. Participants who have taken alendronate for at least 1 year prior to study entry will be assigned to Protocol 1. Participants who have not previously taken alendronate will be assigned to Protocol 2. Participants in both protocols will be randomly assigned to one of the following three biopsy groups: pre-treatment; early; or late. Participants in the pre-treatment biopsy group will have a bone biopsy before treatment begins. Those participants in the early biopsy group will have a biopsy at Week 7 of treatment, and those in the late group will have a biopsy at Month 7.5 of treatment.

Participants will also be randomly assigned to one of three treatment schedules. Participants in Protocol 1 may be assigned to receive alendronate alone for 24 months; teriparatide daily plus alendronate for 24 months; or teriparatide daily on and off for 3 months at a time plus alendronate for 24 months. Participants in Protocol 2 may be assigned to receive only the supplements they were given during the screening visit; teriparatide daily plus alendronate for 24 months; or teriparatide daily on and off for 3 months at a time for 24 months. Participants will attend assessment visits at Weeks 4 and 7 and Months 3, 5, 6, 7.5, 9, 12, 15, 18, 21, and 24. Visits may include bone turnover measurements, bone mass scans, walking tests, questionnaires, CT scans, and blood draws.

A recently funded extension study will extend the treatment period from 24 to 48 months for all consenting. If the individual was assigned to teriparatide daily (with or without alendronate), they will be given alendronate for the 24 to 48 month time period. If the individual was assigned to cyclic teriparatide, they will continue cyclic therapy foro the 24-48 month period (with or without alendronate).

Conditions

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Osteoporosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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1

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.

Group Type EXPERIMENTAL

Teriparatide

Intervention Type DRUG

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

Alendronate

Intervention Type DRUG

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

Calcium

Intervention Type 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.

Vitamin D3

Intervention Type 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.

2

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.

Group Type EXPERIMENTAL

Teriparatide

Intervention Type DRUG

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

Alendronate

Intervention Type DRUG

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

Calcium

Intervention Type 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.

Vitamin D3

Intervention Type 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.

3

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.

Group Type ACTIVE_COMPARATOR

Alendronate

Intervention Type DRUG

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

Calcium

Intervention Type 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.

Vitamin D3

Intervention Type 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.

4

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.

Group Type EXPERIMENTAL

Teriparatide

Intervention Type DRUG

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

Calcium

Intervention Type 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.

Vitamin D3

Intervention Type 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.

5

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.

Group Type EXPERIMENTAL

Teriparatide

Intervention Type DRUG

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

Calcium

Intervention Type 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.

Vitamin D3

Intervention Type 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.

6

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.

Group Type ACTIVE_COMPARATOR

Calcium

Intervention Type 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.

Vitamin D3

Intervention Type 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.

Interventions

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Teriparatide

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

Intervention Type DRUG

Alendronate

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

Intervention Type DRUG

Calcium

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.

Intervention Type DIETARY_SUPPLEMENT

Vitamin D3

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.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

45 Years

Maximum Eligible Age

85 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role collaborator

Health Research, Inc.

OTHER

Sponsor Role collaborator

Helen Hayes Hospital

OTHER

Sponsor Role lead

Responsible Party

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Robert Lindsay

Professor of Clinical Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Robert Lindsay, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Helen Hayes Hospital

Locations

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Helen Hayes Hospital

West Haverstraw, New York, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 36410666 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30355512 (View on PubMed)

Other Identifiers

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R01AR056651-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01 AR056651-01A2, 5RO1 ARO5

Identifier Type: -

Identifier Source: org_study_id

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