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Combination Risedronate - Parathyroid Hormone Trial in Male Osteoporosis (RPM)

This study has been completed.
Sponsor:
Collaborator:
Alliance for Better Bone Health
Information provided by (Responsible Party):
Marcella Walker, Columbia University
ClinicalTrials.gov Identifier:
NCT01611571
First received: May 29, 2012
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to develop new treatment options for osteoporosis in men. The Investigators will study two medications and three treatment regimens. First, risedronate (FDA approved) will be studied as monotherapy. Second, the investigators will study injectable parathyroid hormone (PTH 134, teriparatide; FDA approved), as a therapy for male osteoporosis. PTH, a naturally occurring hormone produced by the parathyroid glands, is one of the most important regulators of bone metabolism. The drug being studied in this protocol, teriparatide, is the first aminoterminal 34 amino acids of the native 84amino acid peptide. Teriparatide contains all of the classical biological activities of native PTH. In studies of postmenopausal women, in a small study of 23 men with osteoporosis and a larger study of 437 men treatment with teriparatide led to significant increases in bone density. Although teriparatide and actonel are now approved for osteoporosis in men additional studies of these medications are needed in order to establish how best to use these drugs. This study is focused on an entirely new treatment approach, namely the combination of two medications for the treatment of osteoporosis risedronate with teriparatide to evaluate whether combination therapy is superior to therapy with either medication alone. This study is also designed to assess the extent to which risedronate maintains increases in bone density after a course of mono or combination therapy.


Condition Intervention Phase
Osteoporosis
Drug: Risedronate
Drug: Teriparatide
Drug: Placebo Teriparatide
Drug: placebo Risedronate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Combination Risedronate - Parathyroid Hormone Trial in Male Osteoporosis

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Change in Spine Bone Density [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    change in spine bone density at 18 months measured by DXA 18 and 24 months


Secondary Outcome Measures:
  • Change in Hip Bone Density [ Time Frame: baseline and 18 months ] [ Designated as safety issue: No ]
    change in hip bone density measured by DXA

  • Change in Forearm Bone Density [ Time Frame: baseline and 18 months ] [ Designated as safety issue: No ]
    change in 1/3 radius of forearm bone density as measured by DXA

  • New Morphometric Vertebral Fractures [ Time Frame: baseline through 18 months ] [ Designated as safety issue: Yes ]
    counting the total new morphometric vertebral fractures as determined by x-ray from baseline through end of study

  • Change in FN BMD at 18 Months [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Change in the Femoral Neck BMD at 18 month


Enrollment: 31
Study Start Date: December 2003
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Active Risedronate Placebo Teriparatide
Active Risedronate + Placebo Teriparatide for 18 months / Active Risedronate for 6 months
Drug: Risedronate
weekly risedronate
Other Names:
  • Risedronate
  • Actonel
  • Risedronic Acid
Drug: Placebo Teriparatide
daily placebo of teriparatide
Other Names:
  • Teriparatide
  • PTH1-34
  • Forteo
Active Comparator: Active Risedronate Active Teriparatide
Active Risedronate + Active Teriparatide for 18 months / Active Risedronate for 6 months
Drug: Risedronate
weekly risedronate
Other Names:
  • Risedronate
  • Actonel
  • Risedronic Acid
Drug: Teriparatide
daily teriparatide
Other Names:
  • Teriparatide
  • PTH1-34
  • Forteo
Active Comparator: Placebo Risedronate Active Teriparatide
Placebo Risedronate Active Teriparatide for 18 months / Active Risedronate for 6 months
Drug: Teriparatide
daily teriparatide
Other Names:
  • Teriparatide
  • PTH1-34
  • Forteo
Drug: placebo Risedronate
weekly placebo of Risedronic Acid
Other Names:
  • Risedronate
  • Risedronic Acid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   30 Years to 85 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males, ages 30-85 with osteoporosis.
  2. Osteoporosis can be due to hypogonadism, past steroid use, or idiopathic.
  3. Patients with hypogonadism can be included if their replacement dosage of testosterone has been stable for at least 18 months.
  4. Bone mineral density must be 2 or more standard deviations below (T-score 2.0) the young adult peak for men at the lumbar spine, the hip or the radius.
  5. Normal renal (glomerular filtration rate >= 60 ml/min) and liver (less than or equal to twice the normal limits for ALT and AST) function.

Exclusion Criteria:

  1. Use of any specific osteoporosis drug in the previous 6 months.
  2. Known or suspected metabolic bone diseases (such as renal osteodystrophy, osteomalacia) other than osteoporosis.
  3. Preexisting hypercalcemia or an underlying hypercalcemic disorder, such as primary hyperparathyroidism.
  4. Secondary hyperparathyroidism.
  5. Paget's disease of bone or fibrous dysplasia. Teriparatide should not be given to patients with these conditions due to an increased risk of osteosarcoma.
  6. Patients with any elevations of alkaline phosphatase that are secondary to bone disease, as such individuals may be at risk for osteosarcoma.
  7. History or presence of any malignancy, except dermatological, but including melanoma. Known or suspected bone metastasis, or a history of skeletal malignancies.
  8. Prior radiation therapy. Patients with prior radiation therapy should be excluded from treatment with teriparatide.
  9. Any medical condition, which in the opinion of the investigator could preclude study participation, including but not limited to cardiovascular, gastric, renal and hepatic disorders, or abnormal PSA test. In particular, patients with active or recent (within the last 2 years) urolithiasis will be excluded.
  10. History of previous major bowel surgery including bowel resection.
  11. Oral use of systematic glucocorticoids for two or more weeks in the previous six months.
  12. Parenteral use of systemic glucocorticoids on more than two occasions in the previous six months.
  13. Use of anticonvulsant drugs.
  14. History of uncontrolled diabetes mellitus (Patient with Type 2 diabetes who have HbA1C< 8 are permitted to be enrolled).
  15. Hypercalciuria (> 4 mg/kg/day).
  16. Impaired liver function (>twice the upper normal limits for ALT and AST).
  17. Hyperadrenalism as assessed by physical examination.
  18. Any other clinically significant laboratory abnormalities, which are deemed relevant to the design of the protocol.
  19. Patients with known hypersensitivity to any of the test materials (teriparatide or risedronate) or related components (metacresol, mannitol, glacial acetic acid, sodium acetate).
  20. Use of any investigational or unlicensed drug in the previous 30 days.
  21. Patients who may be unreliable for the study, including those engaging in excessive alcohol consumption or drug abuse or patients who are unable to return for scheduled follow-up visits.
  22. Patients who are unable or unwilling to comply fully with the protocol.
  23. Inability to stand or sit upright for at least 30 minutes
  24. Those with history of esophagitis, Barrett's esophagus, esophageal/peptic ulcers or esophageal motility disorders
  25. Hypocalcaemia
  26. Renal dysfunction (GFR <60)
  27. Patients planning invasive dental work such as implants, extractions or procedures involving the jaw bone or patients with poor oral hygiene
  28. Use of digitalis.
  29. Patients with HIV/AIDS.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01611571

Locations
United States, New York
Columbia University Medical Center, Harkness Pavilion
New York City, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Alliance for Better Bone Health
Investigators
Principal Investigator: Marcella Walker, MD Columbia University
  More Information

Publications:
Responsible Party: Marcella Walker, Irving Assistant Professor of Clinical Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01611571     History of Changes
Other Study ID Numbers: AAAA4304
Study First Received: May 29, 2012
Results First Received: August 20, 2013
Last Updated: January 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
osteoporosis
male

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases
Bone Diseases, Metabolic
Musculoskeletal Diseases
Etidronic Acid
Risedronic acid
Teriparatide
Bone Density Conservation Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014