OsteoblastNCT00927355
Effect of Thiazolidinediones on Human Bone
A study testing Pioglitazone in people with Osteoblast and Adipocytes, run by Emory University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Osteoblast, Adipocytes, Bone Density
- What is being tested?
- Pioglitazone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2009to Jul 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Thiazolidinediones on Human Bone Marrow Stromal Cell Differentiation Capacity:In Vitro and In Vivo- A Pilot Study
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.
Read the detailed description
E2a. Screening: Prescreening of electronic medical records will be used as much as possible to reduce screen failure rates. Patients will undergo a full history (with special focus on inclusion and exclusion criteria), physical exam, and blood draw. Lab work will consist of CBC, PT, PTT, CMP, HbA1c, PTH, serum beta-HCG in females of childbearing potential and testosterone in males. We will measure 25(OH) Vitamin D at baseline and completion of the study.
E2b. Study visits Subjects will be admitted to the Grady GCRC after an overnight fast at the initial visit and at 26 weeks. Study drug will be dispensed at the initial visit. At the initial visit and at 26 weeks, subjects will undergo bone marrow aspiration by a skilled and certified Hematology Oncology fellow, bone densitometry (DXA) of their hip and spine, and a blood.draw (5mls).
Subjects will be seen in follow-up at the Grady GCRC at 2 weeks and every 4 weeks thereafter for measurement of body weight, vital signs, and targeted history looking for any side effects from study drugs.
Study drug will be dispensed to patients at baseline and on monthly follow-up visits thereafter. To assess compliance, subjects will be instructed to return any unused drug, and if the subject takes less than 75% of the study medication, the patient will be withdrawn from the study. Patients will be monitored closely for development of side effects. Glycemic control will be assessed with HbA1c measurements at baseline, 12 weeks into the study and at end of study. Home blood sugars, fasting and occasional postprandial blood sugars will be assessed at each of the study visits.
E2b.2. Bone Marrow Biopsy aspiration: Bone marrow (BM) aspiration will be done by a hematology and oncology fellow, Dr. Simbo Aduloju, who is certified in doing these procedures at the Grady GCRC. Subjects will be pre-medicated 30 minutes prior to the procedure with oral Lorazepam 2mg and Tylenol 500mg for analgesia.The only absolute contraindication to BM aspirations is the presence of bleeding disorders. During the screening process, patients will be asked about a history of coagulopathies such as hemophilia. In addition all patients will have their PT, PTT and platelets checked at baseline. Under sterile technique and after local anesthesia with 2% lidocaine, 5mls of bone marrow will be aspirated from the posterior iliac crest using a 16 gauge bone marrow aspiration needle attached to a 10 ml syringe. The sample will be placed on ice immediately and transported to the lab of Dr. George Beck. After the procedure, manual pressure will be applied to the aspiration site for a minimum of 5 minutes to prevent bleeding. Patients blood pressure will be checked after the procedure and prior to their departure from the GCRC to ensure absence of hypotension due to lorazepam.
E2b.2.1. Please see section E2c. below for experimental design on procurement of hBMCs from bone marrow aspirates and determination of osteoblast/adipocyte differentiation capacity from these hBMCs.
E2b.3. BMD Evaluation: DXA measurements will be performed at the spine and dominant hip (contralateral hip in the presence of hardware in the dominant hip) using a GE Lunar Prodigy Instrument (GE medical Systems) at Grady Memorial Hospital. The DXA scanner is calibrated on a daily basis with the manufacturer's phantom according to manufacturer guidelines. Short-term root mean square coefficient of variation at our center is 1.1% at the lumbar spine and 1.5% at the total hip.
E2b.4. Laboratory Assays: Bone formation markers (osteocalcin, procollagen type-I N-terminal propeptide [P1NP]) and bone resorption markers (β C-terminal telopeptide of type 1 collagen [β-CTX]) correlate strongly with rates of bone formation and resorption respectively and provide powerful data as they reflect the average bone turnover globally across all bone surfaces in the body. The disadvantage of these markers is that they reflect the final state at the time of sampling and not conditions at any other time point in the experiment.
After an overnight fast, serum will be assayed from subjects between 8 and 9 am to control for diurnal variation. Blood samples will be collected and processed by nurses at the Grady GCRC core laboratory. Serum will be sent to the lab of Dr. George Beck and stored at -80◦C. The following analyses will be done at the end of the study in a single batch for each marker. Please see table 2 for details of each assay.
- Conditions
- Osteoblast, Adipocytes, Bone Density, Osteocalcin, Adiponectin, Mesenchymal Stem Cells
- Being tested
- Pioglitazone, Placebo
- Keywords
- pioglitazone, human bone marrow stem cells, adipocytes, osteoblasts, bone mineral density, adiponectin, leptin, CTX, P1NP, Osteocalcin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (2)
βCTX (Carboxy Terminal Collagen Crosslinks), Osteocalcin, and Adiponectin.
Measured: 6 months
Bone Mineral Density
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2009 (estimated)
- Study startApr 2009
- Primary completionOct 2010
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for OsteoblastStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Natasha Khazai, M.D., Emory University
- Investigators
- Natasha B Khazai, M.D., Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00927355
- Sponsor's protocol ID
- IRB00014509
- Other IDs
- 08006
- Status last verified
- Mar 2016
- First submitted
- 24 Jun 2009
- Last updated
- 29 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 23022285
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Thiazolidinediones on Human Bone Marrow Stromal Cell Differentiation Capacity:In Vitro and In Vivo- A Pilot Study
- ClinicalTrials.gov ID
- NCT00927355
- Acronym / sponsor ID
- IRB00014509
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- Apr 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 25 Jun 2009 (estimated)
- Results
- Posted 2 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
E2a. Screening: Prescreening of electronic medical records will be used as much as possible to reduce screen failure rates. Patients will undergo a full history (with special focus on inclusion and exclusion criteria), physical exam, and blood draw. Lab work will consist of CBC, PT, PTT, CMP, HbA1c, PTH, serum beta-HCG in females of childbearing potential and testosterone in males. We will measure 25(OH) Vitamin D at baseline and completion of the study.
E2b. Study visits Subjects will be admitted to the Grady GCRC after an overnight fast at the initial visit and at 26 weeks. Study drug will be dispensed at the initial visit. At the initial visit and at 26 weeks, subjects will undergo bone marrow aspiration by a skilled and certified Hematology Oncology fellow, bone densitometry (DXA) of their hip and spine, and a blood.draw (5mls).
Subjects will be seen in follow-up at the Grady GCRC at 2 weeks and every 4 weeks thereafter for measurement of body weight, vital signs, and targeted history looking for any side effects from study drugs.
Study drug will be dispensed to patients at baseline and on monthly follow-up visits thereafter. To assess compliance, subjects will be instructed to return any unused drug, and if the subject takes less than 75% of the study medication, the patient will be withdrawn from the study. Patients will be monitored closely for development of side effects. Glycemic control will be assessed with HbA1c measurements at baseline, 12 weeks into the study and at end of study. Home blood sugars, fasting and occasional postprandial blood sugars will be assessed at each of the study visits.
E2b.2. Bone Marrow Biopsy aspiration: Bone marrow (BM) aspiration will be done by a hematology and oncology fellow, Dr. Simbo Aduloju, who is certified in doing these procedures at the Grady GCRC. Subjects will be pre-medicated 30 minutes prior to the procedure with oral Lorazepam 2mg and Tylenol 500mg for analgesia.The only absolute contraindication to BM aspirations is the presence of bleeding disorders. During the screening process, patients will be asked about a history of coagulopathies such as hemophilia. In addition all patients will have their PT, PTT and platelets checked at baseline. Under sterile technique and after local anesthesia with 2% lidocaine, 5mls of bone marrow will be aspirated from the posterior iliac crest using a 16 gauge bone marrow aspiration needle attached to a 10 ml syringe. The sample will be placed on ice immediately and transported to the lab of Dr. George Beck. After the procedure, manual pressure will be applied to the aspiration site for a minimum of 5 minutes to prevent bleeding. Patients blood pressure will be checked after the procedure and prior to their departure from the GCRC to ensure absence of hypotension due to lorazepam.
E2b.2.1. Please see section E2c. below for experimental design on procurement of hBMCs from bone marrow aspirates and determination of osteoblast/adipocyte differentiation capacity from these hBMCs.
E2b.3. BMD Evaluation: DXA measurements will be performed at the spine and dominant hip (contralateral hip in the presence of hardware in the dominant hip) using a GE Lunar Prodigy Instrument (GE medical Systems) at Grady Memorial Hospital. The DXA scanner is calibrated on a daily basis with the manufacturer's phantom according to manufacturer guidelines. Short-term root mean square coefficient of variation at our center is 1.1% at the lumbar spine and 1.5% at the total hip.
E2b.4. Laboratory Assays: Bone formation markers (osteocalcin, procollagen type-I N-terminal propeptide [P1NP]) and bone resorption markers (β C-terminal telopeptide of type 1 collagen [β-CTX]) correlate strongly with rates of bone formation and resorption respectively and provide powerful data as they reflect the average bone turnover globally across all bone surfaces in the body. The disadvantage of these markers is that they reflect the final state at the time of sampling and not conditions at any other time point in the experiment.
After an overnight fast, serum will be assayed from subjects between 8 and 9 am to control for diurnal variation. Blood samples will be collected and processed by nurses at the Grady GCRC core laboratory. Serum will be sent to the lab of Dr. George Beck and stored at -80◦C. The following analyses will be done at the end of the study in a single batch for each marker. Please see table 2 for details of each assay.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: Pioglitazonehalf 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. |
| Placebo | Placebo comparator | Drug: PlaceboThe 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PioglitazoneAlso: Actos6 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. | Drug | Pioglitazone |
| PlaceboThe 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 |
Primary outcome
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.
2 secondary outcomes
βCTX (Carboxy Terminal Collagen Crosslinks), Osteocalcin, and Adiponectin.
Time frame: 6 months
Bone Mineral Density
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23022285Beck 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natasha B Khazai, M.D. principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pioglitazone in people with Osteoblast and Adipocytes, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00927355, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2016; AzTrials last refreshed its copy on 6 Nov 2026.