Effect of Thiazolidinediones on Human Bone

NCT00927355 | Completed Results DMC

• 2 other identifiers: IRB0001450908006
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Osteoblast; Adipocytes; Bone Density; Osteocalcin; Adiponectin; Mesenchymal Stem Cells

Keywords

pioglitazone; human bone marrow stem cells; adipocytes; osteoblasts; bone mineral density; adiponectin; leptin; CTX; P1NP; Osteocalcin

Outcome Measures

Primary Outcomes (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

  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.

  6 months

Secondary Outcomes (2)

• βCTX (Carboxy Terminal Collagen Crosslinks), Osteocalcin, and Adiponectin.

  6 months

• Bone Mineral Density

  6 months

Study Arms (2)

Pioglitazone

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Pioglitazone DRUG

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.

Also known as: Actos

Pioglitazone

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Grady Diabetes Clinic

Atlanta, Georgia, 30303, United States

Location

Related Publications (1)

• Beck GR Jr, Khazai NB, Bouloux GF, Camalier CE, Lin Y, Garneys LM, Siqueira J, Peng L, Pasquel F, Umpierrez D, Smiley D, Umpierrez GE. The effects of thiazolidinediones on human bone marrow stromal cell differentiation in vitro and in thiazolidinedione-treated patients with type 2 diabetes. Transl Res. 2013 Mar;161(3):145-55. doi: 10.1016/j.trsl.2012.08.006. Epub 2012 Sep 27.

  PMID: 23022285 RESULT

MeSH Terms

Interventions

Pioglitazone

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. George Beck
• Organization: Emory

gbeck@emory.edu

404-686-1000

Study Officials

• Natasha B Khazai, M.D.

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assistant professor

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: June 25, 2009
• Study Start: April 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: July 1, 2011
• Last Updated: March 29, 2016
• Results First Posted: June 2, 2014

Record last verified: 2016-03

Locations

US (1)