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

NCT00609362 | Completed Phase 2 Results DMC

• 1 other identifier: 2007-223
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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. 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. 2.The effect on bone turnover will be measured in blood- and urine samples at the same times.
3. 3.The effect on fat distribution will be evaluated by an MRI scan after treatment.
4. 4.The effect on bone marrow cells will be investigated bone marrow sampling immediately after treatment
5. 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

Conditions

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

Keywords

BMD; Rosiglitazone; Bone marrow fat

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Difference in Percent Change in Bone Marrow Fat (Given by a Lipid to Water Ratio) in the Spine.

  Measured at baseline and after 14 weeks of treatment

• Difference in Percent Change in Level of C-terminal Telopeptide (CTx) Between the Rosiglitazone and Placebo Groups

  At baseline and after 14 weeks of treatment

• Change in Gene Expression in Bone Marrow and Fat Cells

  Before and after treatment

Study Arms (2)

Rosiglitazone

ACTIVE COMPARATOR

25 women age 60 to 75 years receiving rosiglitazone 8 mg/day

Drug: Rosiglitazone

Placebo

PLACEBO COMPARATOR

25 women 60 to 75 years of age receiving placebo once a day for 14 weeks

Drug: Placebo pill

Interventions

Rosiglitazone DRUG

one tablet of rosiglitazone 8 milligrams per day for 14 weeks

Also known as: Avandia

Rosiglitazone

Placebo pill DRUG

One encapsulated placebo pill a day for 14 weeks

Placebo

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal women age 60-75 with no rosiglitazone allergy

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8000 C, Denmark

Location

MeSH Terms

Interventions

Rosiglitazone

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Torben Harsløf, MD
• Organization: University of Aarhus

torbhars@rm.dk

+4589497681

Study Officials

• Torben Harsløf, Dr.

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 24, 2008
• First Posted: February 7, 2008
• Study Start: January 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: April 27, 2011
• Results First Posted: April 27, 2011

Record last verified: 2011-03

Locations

DK (1)