Trial record 3 of 92 for:    "ACDC"

Effect of Thiazolidinediones on Human Bone

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Natasha Khazai, M.D., Emory University
ClinicalTrials.gov Identifier:
NCT00927355
First received: June 24, 2009
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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 Intervention
Osteoblast
Adipocytes
Bone Density
Osteocalcin
Adiponectin
Mesenchymal Stem Cells
Drug: Pioglitazone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Official Title: Effects of Thiazolidinediones on Human Bone Marrow Stromal Cell Differentiation Capacity:In Vitro and In Vivo- A Pilot Study

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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:
  • βCTX (Carboxy Terminal Collagen Crosslinks), Osteocalcin, and Adiponectin. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Bone Mineral Density [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: April 2009
Study Completion Date: July 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00927355

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

Publications:
Responsible Party: Natasha Khazai, M.D., assistant professor, Emory University
ClinicalTrials.gov Identifier: NCT00927355     History of Changes
Other Study ID Numbers: IRB00014509, 08006
Study First Received: June 24, 2009
Results First Received: July 9, 2013
Last Updated: June 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
pioglitazone
human bone marrow stem cells
adipocytes
osteoblasts
bone mineral density
adiponectin
leptin
CTX
P1NP
Osteocalcin

Additional relevant MeSH terms:
Pioglitazone
2,4-thiazolidinedione
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014