PaTH Study: Parathyroid Hormone and Alendronate for Osteoporosis - Full Text View

Sponsor:	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:	NCT00005005

Purpose

This 2-year study will test the effectiveness of combining parathyroid hormone (PTH) and alendronate for treating osteoporosis in postmenopausal women. Alendronate is a drug used to treat osteoporosis and primarily prevents bone loss, whereas PTH increases bone formation. We will treat the study participants either with PTH and alendronate, alendronate alone, or PTH alone. We will determine the effects of these treatments by looking for changes in bone mineral density in the hip and spine.

Condition	Intervention	Phase
Osteoporosis	Drug: PTH Drug: Alendronate	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	Clinical Trial of Parathyroid Hormone (PTH) and Alendronate in Combination in the Treatment of Osteoporosis

Resource links provided by NLM:

MedlinePlus related topics: Bone Density Minerals Osteoporosis

Drug Information available for: Alendronate Alendronate sodium Fosamax Parathyroid

U.S. FDA Resources

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

Primary Outcome Measures:

Changes in bone mineral density at several sites and changes in biochemical markers [ Time Frame: Year 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Predictive value of specific biochemical markers of bone turnover [ Time Frame: Year 2 ] [ Designated as safety issue: No ]

Enrollment:	238
Study Start Date:	October 1999
Study Completion Date:	November 2007
Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will receive PTH for 1 year followed by alendronate for 1 year.	Drug: PTH Drug: Alendronate
Experimental: 2 Participants will receive PTH and alendronate for 1 year followed by alendronate for 1 year.	Drug: PTH Drug: Alendronate
Experimental: 3 Participants will receive alendronate for 2 years.	Drug: Alendronate
Active Comparator: 4 Participants will receive PTH for 1 year followed by placebo for 1 year.	Drug: PTH

Detailed Description:

The PaTH study is a 2-year, multicenter, double-blind, placebo-controlled trial to test the efficacy of combining hPTH (1-84) and alendronate for treating osteoporosis in postmenopausal women.

238 women were randomized between 55 and 85 years of age to receive either: (1) PTH for 1 year followed by alendronate for 1 year; (2) PTH and alendronate for 1 year followed by alendronate for 1 year; (3) alendronate for 2 years; or (4) PTH for 1 year followed by placebo for 1 year. The primary endpoints are changes in bone mineral density at several sites and changes in biochemical markers.

In addition, we will assess specific biochemical markers of bone turnover (e.g., osteocalcin, deoxypridinoline, N-telopeptide, bone-specific alkaline phosphatase and bone sialoprotein) to determine if they can predict the skeletal response to combination therapy. We will also determine whether PTH positively affects ultrasound measurements in the calcaneus.

Eligibility

Ages Eligible for Study:	55 Years to 85 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Aged between 55 and 85 years
Postmenopausal (have not had any menses in the last 5 years)
Have a bone mineral density scan (DXA) that can be evaluated at the spine AND at the hip with a T-score equal to or below -2.5 at the spine or the femoral neck or total hip OR T-score equal to or below -2.0 at the spine or the femoral neck or total hip and have at least one of the following risk factors for fracture: (a) age > 65 years; (b) history of postmenopausal fracture (nonvertebral or vertebral); or (c) maternal history of hip fracture
Willing and able to self-administer daily injections

Exclusion Criteria:

Have used estrogen (oral or patch) for more than 1 month in the last 6 months or more than 12 months in the last 2 years
History of more than 12 months of bisphosphonate use ever, or any use (> 4 weeks) within the past 12 months
History of rhPTH (recombinant human PTH) use
Any major life-threatening illnesses
Type 1 or uncontrolled type 2 diabetes mellitus (defined as hemoglobin A1C > 10.0), or currently using insulin
Vitamin D level < 15 nanograms/ml
History of kidney disease (creatinine > 2.0 mg/dl)
Renal insufficiency (creatinine clearance < 40 mg/min)
Any history of kidney stones
Any history of hypercalciuria or currently have urine calcium/creatinine >300 mg
History of hypercalcemia, sarcoidosis, or hyperparathyroidism
History of active or treated tuberculosis or other granulomatous disorders
History of breast cancer, melanoma, or hematologic malignancy that has required treatment within the last 10 years
History of bone cancer or any other metabolic bone disease that has required treatment within the last 10 years
History of any other nonskin cancer that has required treatment within the last 10 years
History of symptomatic esophageal reflux, achalasia or esophageal stricture
Currently taking > 7.5 mg systemic prednisone or equivalent per day
Currently using > two puffs, four times/day of inhaled steroids
Currently taking anticoagulants or anticonvulsants
Have used Calcitonin within the past 3 months
Have used Raloxifene in the last 6 months or for more than 12 months in the last 2 years
Have used Tamoxifen in the last 6 months or for more than 12 months in the last 2 years
Have used fluoride for at least a month within the past 5 years
Currently taking > 1000 IU/day vitamin D or vitamin D analogues or metabolites
Currently taking thyroid hormone replacement AND have a TSH < 0.1mIU/L

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005005

Locations

United States, Maine
Maine Center for Osteoporosis
Bangor, Maine, United States, 04401
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55415
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

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

Investigators

Principal Investigator:

Dennis Black, PhD

University of California, San Francisco

More Information

Publications:

Black DM, Greenspan SL, Ensrud KE, Palermo L, McGowan JA, Lang TF, Garnero P, Bouxsein ML, Bilezikian JP, Rosen CJ; PaTH Study Investigators. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003 Sep 25;349(13):1207-15. Epub 2003 Sep 20.

Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, McGowan JA, Rosen CJ; PaTH Study Investigators. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. N Engl J Med. 2005 Aug 11;353(6):555-65.

Bauer DC, Garnero P, Bilezikian JP, Greenspan SL, Ensrud KE, Rosen CJ, Palermo L, Black DM. Short-term Changes in Bone Turnover Markers and Bone Mineral Density Response to Parathyroid Hormone in Postmenopausal Women with Osteoporosis. J Clin Endocrinol Metab. 2006 Jan 31; [Epub ahead of print]

Sellmeyer DE, Black DM, Palermo L, Greenspan S, Ensrud K, Bilezikian J, Rosen CJ. Hetereogeneity in skeletal response to full-length parathyroid hormone in the treatment of osteoporosis. Osteoporos Int. 2007 Feb 28; [Epub ahead of print]

Antoniucci DM, Sellmeyer DE, Bilezikian JP, Palermo L, Ensrud KE, Greenspan SL, Black DM. Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis. J Clin Endocrinol Metab. 2007 Mar;92(3):942-7. Epub 2006 Dec 12.

Responsible Party:	Dr. Dennis Black, University of California San Francisco
ClinicalTrials.gov Identifier:	NCT00005005 History of Changes
Other Study ID Numbers:	N01 AR92245, NIAMS-045
Study First Received:	March 24, 2000
Last Updated:	September 19, 2008
Health Authority:	United States: Food and Drug Administration

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

PTH
Alendronate
Parathyroid hormone
Osteoporosis
Postmenopausal

Additional relevant MeSH terms:

Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Hormones

Alendronate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on February 12, 2012