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Effect of Thiazolidinediones on Human Bone

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00927355
Recruitment Status : Completed
First Posted : June 25, 2009
Results First Posted : June 2, 2014
Last Update Posted : March 29, 2016
Information provided by (Responsible Party):
Natasha Khazai, M.D., Emory University

Brief Summary:
We will prospectively study 2 groups of diabetic patients treated with pioglitazone or placebo for 26 weeks. Bone marrow aspirates will be obtained from these patients at baseline and after 26 weeks of treatment, and hBMCs will be isolated from these bone marrow aspirations. The ability of hBMCs to differentiate into osteoblast and adipocytes lineages will be compared before and after treatment with pioglitazone and compared to placebo. In parallel, clinical markers of bone formation and resorption as well as bone mineral density will be assessed before and after 26 weeks of treatment. Primary endpoint for this study will be detection of change in number of osteoblasts or adipocytes from cultured hBMCs between study groups and within each group.

Condition or disease Intervention/treatment Phase
Osteoblast Adipocytes Bone Density Osteocalcin Adiponectin Mesenchymal Stem Cells Drug: Pioglitazone Drug: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Official Title: Effects of Thiazolidinediones on Human Bone Marrow Stromal Cell Differentiation Capacity:In Vitro and In Vivo- A Pilot Study
Study Start Date : April 2009
Actual Primary Completion Date : October 2010
Actual Study Completion Date : July 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Pioglitazone
half of the diabetic patients will be randomized to pioglitazone treatment for 6 months starting out with 15mg qd for 4 weeks and dose increased to 30mg (2 tablets) qday if no adverse effects noted at the four week mark by study physician.
Drug: Pioglitazone
6 month treatment with pioglitazone 15mg for four weeks with dose increased to 30mg if no adverse effects (swelling of lower extremities, liver enzyme elevation) noted at the four week mark.
Other Name: Actos

Placebo Comparator: Placebo
The other half will be randomized to placebo for 6 months. The placebo pills also start out with one "15mg) pill qday and are increased to 2 tablets ("30mg") qday after 4 weeks if no adverse effects are noted by study physician.
Drug: Placebo
The placebo pills also start out with one ("15mg") pill qday and are increased to 2 tablets ("30mg") qday after 4 weeks if no adverse effects are noted by study physician.

Primary Outcome Measures :
  1. Percent Change in Number of Osteoblast and Adipocyte Colony Forming Units Cultured From Bone Marrow Stem Cells Harvested 6 Months After Treatment With Study Drug Compared to Baseline [ Time Frame: 6 months ]
    To determine the effect of PIO (pioglitazone) on BMSC (bone marrow stem cell) lineage choice in vivo, a bone marrow aspiration was obtained from patients at baseline and after 6 months of treatment with PIO or placebo. The bone marrow was used for ex vivo CFU-OB (Colony forming units-Osteoblast) and CFU-AD assays using the same protocol described for the in vitro studies previously. We also analyzed the number of total colonies per patient at both baseline and final visit.

Secondary Outcome Measures :
  1. βCTX (Carboxy Terminal Collagen Crosslinks), Osteocalcin, and Adiponectin. [ Time Frame: 6 months ]
  2. Bone Mineral Density [ Time Frame: 6 months ]

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:Subjects with T2DM who are:

  • naïve to insulin and TZD therapy
  • On diet and lifestyle therapy along with submaximal metformin therapy
  • with HbA1c between 7% and 8.0%
  • between the ages of 18 and 80 years
  • both genders

Exclusion Criteria:

  • Contraindications to TZD therapy including congestive heart failure class III or IV, and/or macular edema
  • history of osteoporosis (T score < -2.5 on DXA scanning) or osteoporotic fragility fracture
  • treatment with glucocorticoids within 1 year of study enrollment
  • treatment with bisphosphonates,calcitriol, raloxifene, Calcitonin, estrogen
  • vitamin D insufficiency, defined as 25(OH)D levels <30 ng/mL or
  • hyperparathyroidism
  • liver disease (LFTS > 3x upper limits of normal)
  • Kidney disease Cr>1.4 in females and Cr>1.5 in males
  • smokers (active or within a month from stopping)
  • alcohol or drug abuse/dependence
  • hypogonadism in males
  • mental conditions rendering the subject unable to understand the scope of the study
  • female subjects who are pregnant or breast feeding
  • chronic obstructive pulmonary disease
  • obstructive sleep apnea.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00927355

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United States, Georgia
Grady Diabetes Clinic
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
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Principal Investigator: Natasha B Khazai, M.D. Emory University

Publications of Results:
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Responsible Party: Natasha Khazai, M.D., assistant professor, Emory University Identifier: NCT00927355     History of Changes
Other Study ID Numbers: IRB00014509
08006 ( Other Identifier: Other )
First Posted: June 25, 2009    Key Record Dates
Results First Posted: June 2, 2014
Last Update Posted: March 29, 2016
Last Verified: March 2016

Keywords provided by Natasha Khazai, M.D., Emory University:
human bone marrow stem cells
bone mineral density

Additional relevant MeSH terms:
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Hypoglycemic Agents
Physiological Effects of Drugs