Bisphosphonate Action on the Appendicular Skeleton: Evidence for Differential Effects

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Procter and Gamble
University of Sheffield
Information provided by:
Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00666627
First received: April 23, 2008
Last updated: June 14, 2012
Last verified: June 2012
  Purpose

A study to determine if the three licensed bisphosphonates (alendronate, ibandronate and risedronate):a) affect the peripheral skeleton differently, as assessed by quantitative ultrasound of bone (QUS), peripheral quantitative computed tomography (pQCT) and dual−energy x−ray absorptiometry (DXA)? b) have different effects on bone cells and their activity as assessed by flow cytometry and biochemical markers of bone cell activity? The aim of the study is to compare the effects of three licensed bisphosphonates on bone quantity and quality. There has been no such study before. Most of the measures of bone quantity and quality used in this protocol have not been studied with any of these three agents. The novelty of the study necessitates the establishment of reference ranges and this explains the need for the inclusion of a group of young women.


Condition Intervention Phase
Post-menopausal Osteoporosis
Drug: Ibandronate
Drug: Risedronate
Drug: Alendronate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 2-year Randomised Parallel Group Trial of Alendronate, Ibandronate and Risedronate for Postmenopausal Osteoporosis in Secondary Care.

Resource links provided by NLM:


Further study details as provided by Sheffield Teaching Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Change in heel broadband ultrasound attenuation [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in the percentage of MCSFR+ monocytes in the peripheral blood at baseline and after one week and 48 weeks of therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change in SOS at finger and heel at 48 weeks. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change in lumbar spine and total hip BMD measured by DXA at 48 weeks [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change in finger BMD measured by RA at 48 weeks [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change in heel BMD measured by DXL at 48 weeks [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change in distal tibia and ultradistal forearm cortical and trabecular volumetric BMD by pQCT at 48 weeks [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Changes in cathepsin K and MM enzyme and OPG and RANK-L protein at 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Changes in uNTX and uCTX. At 12 weeks [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Change in disulfide bond content of nails at 48 weeks [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 410
Study Start Date: April 2007
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Ibandronate
Drug: Ibandronate
once monthly
Other Name: Bonviva
Active Comparator: 2
Risedronate
Drug: Risedronate
Risedronate 35mg once weekly
Other Name: Actonel
Active Comparator: 3
Alendronate 70mg once weekly
Drug: Alendronate
Alendronate 70mg once weekly
Other Name: Fosamax
No Intervention: 4
Young women control group

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • be female
  • at least 5 years post menopausal but <85 years
  • BMD T-score (at the lumbar spine or total hip) of less than or equal to

    • 2.5, or T-score less than or equal to -1 with a low trauma fracture.
  • be ambulatory
  • be able and willing to participate in the study and provide written informed consent

Exclusion Criteria:

  • have evidence of a clinically significant organic disease which could prevent the patient from completing the study
  • have a BMI less than 18 or greater than 35
  • abuse alcohol or use illicit drugs or who consumed more than 4 servings of any alcoholic beverage one day prior to the visit (i.e., subjects who might be binge drinkers)
  • have any history of cancer within the past 5 years excluding skin cancer non melanomas
  • have a history of ongoing conditions or diseases known to cause abnormalities of calcium metabolism or skeletal health (secondary osteoporosis)
  • Chronic renal disease (as defined by a creatinine clearance of ≤ 30ml/min)
  • Acute or chronic hepatic disease
  • Malabsorption syndromes
  • Hyperthyroidism as manifested by TSH outside the lower limit of the normal range
  • Hyperparathyroidism
  • Hypocalcemia or hypercalcemia
  • Osteomalacia
  • Cushing's syndrome
  • Patient who are currently on glucocorticoid therapy
  • have a serum calcium less than 2.2 mmol/l and a PTH above 75ng/l
  • have a history of any known condition that would interfere with the assessment of DXA at either lumbar spine or femoral neck
  • have markedly abnormal clinical laboratory parameters that are assessed as clinically significant by the investigator
  • use any of the following medications within 12 months of starting study drug

    • Bisphosphonates (at any dose)
    • Use of any fluoride with the exception use for oral hygiene
    • Strontium
    • Other bone agents (i.e., SERM, isoflavones, HRT etc)
  • have participated in another clinical trial involving active therapy 3 months prior to randomisation
  • have a history of allergic reaction to bisphosphonates
  • patient taking calcium supplements within the last month prior to randomisation
  • We will exclude patients with secondary osteoporosis, those who have been on anti-resorptive treatments in the past year, and women less than 5 years since menopause, and those with bilateral fractures in the measurement regions (heel, hip and forearm).
  • Have suffered a recent fracture within the last 12 months
  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: NCT00666627

Locations
United Kingdom
Academic Unit of Bone Metabolism (Sheffield)
Sheffield, South Yorkshire, United Kingdom, S5 7AU
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Procter and Gamble
University of Sheffield
Investigators
Study Director: Eugene McCloskey, Dr University of Sheffield
Study Director: Rosemary Hannon, Dr University of Sheffield
Study Director: Angela Rogers, Dr University of Sheffield
Study Director: Margaret Paggiosi, Dr University of Sheffield
  More Information

No publications provided

Responsible Party: Professor Richard Eastell, University of Sheffield
ClinicalTrials.gov Identifier: NCT00666627     History of Changes
Other Study ID Numbers: STH 14463
Study First Received: April 23, 2008
Last Updated: June 14, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
Osteoporosis
Post-menopausal osteoporosis
Bisphosphonates
Alendronate
Ibandronate
Risedronate

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

ClinicalTrials.gov processed this record on July 20, 2014