Continuous Versus Cyclic Treatment With Teriparatide and Alendronate Combined or Teriparatide Alone in Women With Osteoporosis - Full Text View

Sponsored by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by:	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:	NCT00668941

Purpose

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.

Condition	Intervention
Osteoporosis	Drug: Teriparatide Drug: Alendronate Dietary Supplement: Calcium Dietary Supplement: Vitamin D3

MedlinePlus related topics: Calcium Dietary Supplements Osteoporosis

Drug Information available for: Alendronate Alendronate sodium Calcium gluconate Vitamin D Ergocalciferol Cholecalciferol Teriparatide Teriparatide acetate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:	A Mechanistic Study of Skeletal Actions of 1-34hPTH

Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Primary Outcome Measures:

Bone density [ Time Frame: Measured at Month 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Histomorphometry of iliac crest bone biopsies [ Time Frame: Measured at Week 7 and Month 7 ] [ Designated as safety issue: No ]

Estimated Enrollment:	140
Study Start Date:	September 2005
Estimated Study Completion Date:	May 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 24 months, in addition to alendronate. Biopsies will be performed at Week 7 or Month 7.5.	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 24 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.
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. Biopsies will be performed at Week 7 or Month 7.5.	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 24 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.
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 Participants will take 70 mg per week of alendronate for 24 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.
4: Experimental Participants in this group will receive a continuous regimen of teriparatide (20 mcg delivered subcutaneously) daily for 24 months. Biopsies will be performed at Week 7 or Month 7.5.	Drug: Teriparatide Teriparatide will be given subcutaneously in 20-mcg doses either continuously or cyclically. 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.
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. Biopsies will be performed at Week 7 or Month 7.5.	Drug: Teriparatide Teriparatide will be given subcutaneously in 20-mcg doses either continuously or cyclically. 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.
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 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.

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 in this 2-year study will first attend a screening visit that will include 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.

Eligibility

Ages Eligible for Study:	45 Years to 85 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00668941

Contacts

Contact: Nancy Barbuto, RN

845-786-4804

barbuton@helenhayeshosp.org

Locations

United States, New York
Helen Hayes Hospital	Recruiting
West Haverstraw, New York, United States, 10993
Contact: Nancy Barbuto 845-786-4804 barbuton@helenhayeshosp.org
Sub-Investigator: Felicia Cosman, MD
Sub-Investigator: David W. Dempster, PhD
Sub-Investigator: Jeri W. Nieves, PhD

Sponsors and Collaborators

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

Investigators

Principal Investigator:

Robert Lindsay, MD, PhD

Helen Hayes Hospital

More Information

Responsible Party:	Helen Hayes Hospital ( Robert Lindsay, MD, PhD )
Study ID Numbers:	R01 AR051454
Study First Received:	April 27, 2008
Last Updated:	October 6, 2008
ClinicalTrials.gov Identifier:	NCT00668941
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Bone Density
Bone Turnover
Histomorphometry

Study placed in the following topic categories:

Calcium, Dietary
Cholecalciferol
Vitamin D
Musculoskeletal Diseases
Teriparatide

Alendronate
Ergocalciferols
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases

Additional relevant MeSH terms:

Growth Substances
Vitamins
Physiological Effects of Drugs

Bone Density Conservation Agents
Micronutrients
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009