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Cyclic Versus Daily Teriparatide on Bone Mass

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ClinicalTrials.gov Identifier: NCT00668941
Recruitment Status : Unknown
Verified August 2017 by Robert Lindsay, Helen Hayes Hospital.
Recruitment status was:  Active, not recruiting
First Posted : April 29, 2008
Last Update Posted : August 10, 2017
Sponsor:
Collaborators:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Health Research, Inc.
Information provided by (Responsible Party):
Robert Lindsay, Helen Hayes Hospital

Tracking Information
First Submitted Date  ICMJE April 27, 2008
First Posted Date  ICMJE April 29, 2008
Last Update Posted Date August 10, 2017
Study Start Date  ICMJE September 2005
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2011)
Bone density [ Time Frame: 24 and 48 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 28, 2008)
Bone density [ Time Frame: Measured at Month 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2011)
  • Histomorphometry of iliac crest bone biopsies [ Time Frame: Measured at Week 7 and Month 7 ]
  • HRpQCT (tibia, radius) and QCT (spine and hip)and FEA of these QCT scans [ Time Frame: 48 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2008)
Histomorphometry of iliac crest bone biopsies [ Time Frame: Measured at Week 7 and Month 7 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cyclic Versus Daily Teriparatide on Bone Mass
Official Title  ICMJE Cyclic Versus Daily Teriparatide on Bone Mass
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.
Detailed Description

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Osteoporosis
Intervention  ICMJE
  • Drug: Teriparatide
    Teriparatide will be given subcutaneously in 20-mcg doses either continuously or cyclically.
  • Drug: Alendronate
    Participants will take 70 mg per week of alendronate for 48 months.
  • Dietary Supplement: 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.
  • 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.
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Teriparatide
    • Drug: Alendronate
    • Dietary Supplement: Calcium
    • Dietary Supplement: Vitamin D3
  • Experimental: 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.
    Interventions:
    • Drug: Teriparatide
    • Drug: Alendronate
    • Dietary Supplement: Calcium
    • Dietary Supplement: Vitamin D3
  • Active Comparator: 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.
    Interventions:
    • Drug: Alendronate
    • Dietary Supplement: Calcium
    • Dietary Supplement: Vitamin D3
  • Experimental: 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.
    Interventions:
    • Drug: Teriparatide
    • Dietary Supplement: Calcium
    • Dietary Supplement: Vitamin D3
  • Experimental: 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.
    Interventions:
    • Drug: Teriparatide
    • Dietary Supplement: Calcium
    • Dietary Supplement: Vitamin D3
  • Active Comparator: 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.
    Interventions:
    • Dietary Supplement: Calcium
    • Dietary Supplement: Vitamin D3
Publications * 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 Naïve and alendronate treated women. Bone. 2019 Mar;120:246-253. doi: 10.1016/j.bone.2018.10.020. Epub 2018 Oct 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: April 28, 2008)
140
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2017
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 45 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00668941
Other Study ID Numbers  ICMJE R01 AR056651-01A2, 5RO1 ARO5
R01AR056651-01A2 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Robert Lindsay, Helen Hayes Hospital
Study Sponsor  ICMJE Helen Hayes Hospital
Collaborators  ICMJE
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  • Health Research, Inc.
Investigators  ICMJE
Principal Investigator: Robert Lindsay, MD, PhD Helen Hayes Hospital
PRS Account Helen Hayes Hospital
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP