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Changes in Knee Articular Cartilage Volume in Women on Aromatase Inhibitors
This study is currently recruiting participants.
Verified by Monash University, May 2005
Sponsored by: Monash University
Information provided by: Monash University
ClinicalTrials.gov Identifier: NCT00111241
  Purpose

Many women with breast cancer are treated with a class of drugs called aromatase inhibitors (mainly letrozole or anastrozole), which lowers the amount of estrogen being produced in the body. Women on aromatase inhibitors appear to experience joint pains and arthralgia. The aim of this study is to determine whether the joint pains experienced by some women on aromatase inhibitors is associated with more defects in their cartilage, compared to women not receiving this therapy. Using the magnetic resonance imaging (MRI) technique, the knee joint will be examined to assess changes in cartilage volume over time.


Condition Intervention Phase
Arthralgia
Drug: aromatase inhibitors (letrozole, anastrozole)
Phase IV

Genetics Home Reference related topics: breast cancer
Drug Information available for: Anastrozole Letrozole
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Historical Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Assessment of Knee Joint Articular Cartilage Volume Change, Bone Loss and Change in Body Composition in Women Treated With Anastrozole or Letrozole and Comparison With Untreated Controls

Further study details as provided by Monash University:

Primary Outcome Measures:
  • Knee cartilage volume

Secondary Outcome Measures:
  • Menopausal symptoms
  • Well-being

Estimated Enrollment: 170
Study Start Date: May 2005
Estimated Study Completion Date: June 2008
Detailed Description:

The mechanism of increased bone loss and fracture risk is clearly related to the depletion of estrogen production in the bone. But why there is a higher rate of reporting arthralgia, fracture and joint pain amongst women on aromatase inhibitors is not understood.

Using magnetic resonance imaging (MRI) to measure knee articular cartilage volume, we have demonstrated that post menopausal hormone therapy used for at least five years is associated with retention of articular cartilage in the knee, indicating that oestrogen may protect against the development of osteoarthritis in post menopausal women. Furthermore, we have recently observed that free testosterone is associated with loss of tibial cartilage, after taking into account age, body mass index, baseline tibial cartilage volume, tibial plateau area and total bone mineral content in healthy men. Whether an excess of testosterone to oestrogen as a consequence of aromatase inhibition has an adverse effect on articular cartilage volume warrants further investigation.

This study will include non-hysterectomised women aged 40 to 65 years who have undergone breast surgery and then commenced on aromatase inhibitors within the preceding 12 weeks. The control group (which has been fully recruited) included non-hysterectomised, healthy women aged 40 to 65 years. A MRI of the dominant knee will be used to compare changes in knee articular volume over time. A MRI will be done at baseline and again at 2 years. Changes in knee articular volume is the primary outcome. We will also use this opportunity to compare menopausal symptoms (assessed using the Menopause Quality of Life [MENQOL] questionnaire) between women treated with aromatase inhibitors and those who are not. Well-being will also be assessed using the Psychological General Well-Being index.

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Group 1 :

  • Aged 40 - 65
  • Non-hysterectomised women who have undergone breast surgery
  • Women on aromatase inhibitors within preceding 12 weeks

Group 2 : control group

  • Healthy, non-hysterectomised women aged 40-65 .

Exclusion Criteria:

  • Previous knee injury requiring non-weight bearing treatment for > 24 hrs or surgery (including arthroscopy)
  • Inability to complete the study (eg proposed relocation)
  • Contraindication to undergoing an MRI including pacemaker, metal sutures, presence of shrapnel, iron filings in eye
  • Claustrophobia

Additional Exclusions for Group 1

  • Treatment with tamoxifen for > 8 weeks prior to commencement
  • Knee pain lasting for >24 hours in the last 5 years (prior to commencement on anastrozole or letrozole)
  • Anastrazole or Letrozole therapy for > 12 weeks
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00111241

Locations
Australia, Victoria
Women's Health Program, Monash University Recruiting
Melbourne, Victoria, Australia, 3181
Contact: Susan Davis, Professor     +61 3 9903 0827     susan.davis@med.monash.edu.au    
Contact: Rebecca Ades, MPH     +61 3 9903 0827     Rebecca.ades@med.monash.edu.au    
Sub-Investigator: Robin Bell, MBBS PhD MPH FAFPHM            
Principal Investigator: Susan Davis, MBBS FRACP PhD            
Sponsors and Collaborators
Monash University
Investigators
Principal Investigator: Susan Davis, MBBS FRACP PhD Director Women's Health Program
  More Information

Study ID Numbers: 2004/949
Study First Received: May 18, 2005
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00111241  
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by Monash University:
bone fracture
cartilage
osteoporosis
breast cancer
aromatase inhibitors
knee articular cartilage volume

Study placed in the following topic categories:
Signs and Symptoms
Anastrozole
Musculoskeletal Diseases
Joint Diseases
Fractures, Bone
Osteoporosis
Breast Neoplasms
Letrozole
Pain
Arthralgia

Additional relevant MeSH terms:
Antineoplastic Agents, Hormonal
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Aromatase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009