Official Title: “A Mechanistic Study of Skeletal Actions of 1-34hPTH”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Single Blind (Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: May 2010

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.

Intervention(s) in this Clinical Trial

• 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.

Arms, Groups and Cohorts in this Clinical Trial

• 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 24 months, in addition to alendronate. Biopsies will be performed at Week 7 or Month 7.5.
• 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. Biopsies will be performed at Week 7 or Month 7.5.
• 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.
• Experimental: 4
  • 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.
• 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. Biopsies will be performed at Week 7 or Month 7.5.
• 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.

Primary Measures

• Bone density
  • Time Frame: Measured at Month 24
    Safety Issue?: No

Secondary Measures

• Histomorphometry of iliac crest bone biopsies
  • Time Frame: Measured at Week 7 and Month 7
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 45 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Overall Clinical Trial Officials and Contacts

Robert Lindsay, MD, PhD Principal Investigator Helen Hayes Hospital  

Overall Contact: Nancy Barbuto, RN 845-786-4804 barbuton@helenhayeshosp.org

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00668941

Study ID Number: R01 AR051454

ClinicalTrials.gov Identifier: NCT00668941

Health Authority: United States: Federal Government