The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells

Change in Bone Mineral Density Clinical Trial

Official title:

The Effect of Glitazone Treatment on Bone Marrow and Bone Marrow Cells

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00609362
• Other study ID #: 2007-223
• Status: Completed
• Phase: Phase 2
• First received: January 24, 2008
• Last updated: March 29, 2011
• Start date: January 2008
• Est. completion date: November 2009

Study information

• Verified date: March 2011
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

Osteoporosis is a generalised bone disease leading to an increased risk of fractures. The disease is caused partly by environmental and partly by genetic factors. It is well known that the fat content of the bone marrow is increased in osteoporotic patients. Animal studies suggest that stimulation of bone marrow stem cells through the molecule PPARgamma with the drug rosiglitazone converts the stem cells to fat cells instead of bone cells thereby decreasing bone strength. In a single study healthy volunteers were treated with rosiglitazone for 14 weeks and had a decrease in bone mineral density.

In the present study we wish to investigate the effect of this treatment on bone and fat tissue. 25 women above the age of 60 will be treated with rosiglitazone 8 mg/day for 14 weeks and compared with 25 women receiving placebo.

The effect will be evaluated as follows:

1. The effect on bone marrow density will be examined by a bone scan prior to and after treatment and again after 6 and 9 months.

2. The effect on bone turnover will be measured in blood- and urine samples at the same times.

3. The effect on fat distribution will be evaluated by an MRI scan after treatment.

4. The effect on bone marrow cells will be investigated bone marrow sampling immediately after treatment

5. The direct effect on fat will be examined by a biopsy immediately after treatment The study hypothesis is that rosiglitazone treatment decreases bone mineral density and increases bone marrow fat content. The causal molecular mechanisms will be investigated from the bone marrow and fat samples

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 60 Years to 75 Years

Eligibility

Inclusion Criteria:

• Postmenopausal women age 60-75 with no rosiglitazone allergy

Exclusion Criteria:

• Osteoporosis

• Diabetes

• Hyperthyroidism, untreated hypothyroidism, hyperparathyroidism

• Treatment with bone active drugs

• Low impact fracture

• Heart disease

• Kidney failure

• Liver failure

• Anaemia

• Ineligibility for MRI-scan

• Cancer within last 5 years

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Change in Bone Marrow Fat Content
• Change in Bone Mineral Density

Intervention

Drug:
• Rosiglitazone
one tablet of rosiglitazone 8 milligrams per day for 14 weeks
• Placebo pill
One encapsulated placebo pill a day for 14 weeks

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in Percent Change in Bone Mineral Density (BMD) From Baseline to 14 Weeks Between the Rosiglitazone Group and the Placebo Group	Difference in percent change in bone mineral density (BMD) from baseline to 14 weeks between the rosiglitazone group and the placebo group. BMD was assesed using dual x-ray absorptiometry (DXA)	BMD measured at baseline and after 14 weeks of treatment	No
Secondary	Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine.	Bone marrow fat was measured using MRI spectroscopy providing a measure of bone marrow fat as a ratio to bone marrow water, the lipid-water ratio (LWR)	Measured at baseline and after 14 weeks of treatment	No
Secondary	Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups	C-terminal telopeptide is a marker of bone resorption. Its levels are measure in plasma using a chemiluminometric method (ECLIA).	At baseline and after 14 weeks of treatment	No
Secondary	Change in Gene Expression in Bone Marrow and Fat Cells		Before and after treatment	No