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Name:
UMIN ID:

Recruitment status Terminated
Unique ID issued by UMIN UMIN000004189
Receipt No. R000005033
Scientific Title Crossover trial comparing sera obtained from diabetic patients before and after pioglitazone administration on cholesterol efflux from macrophages
Date of disclosure of the study information 2010/09/15
Last modified on 2013/09/12

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Basic information
Public title Crossover trial comparing sera obtained from diabetic patients before and after pioglitazone administration on cholesterol efflux from macrophages
Acronym Pioglitazone and cholesterol efflux
Scientific Title Crossover trial comparing sera obtained from diabetic patients before and after pioglitazone administration on cholesterol efflux from macrophages
Scientific Title:Acronym Pioglitazone and cholesterol efflux
Region
Japan

Condition
Condition Diabetes
Classification by specialty
Endocrinology and Metabolism
Classification by malignancy Others
Genomic information NO

Objectives
Narrative objectives1 To investigate whether pioglitazone enhance cholesterol efflux and ABCA1/G1 expressions in macrophages, we plan to obtain blood from diabetic patients before and after orally administtation of pioglitazone, and compare them.
Basic objectives2 Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes Macrophage ABCA1/G1 expressions and cholesterol efflux cultured under sera obtained from diabetic patients
Key secondary outcomes

Base
Study type Interventional

Study design
Basic design Cross-over
Randomization Randomized
Randomization unit
Blinding Open -but assessor(s) are blinded
Control Placebo
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms 2
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 Oral administration of pioglitazone
Interventions/Control_2 Oral administration of placebo
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit
20 years-old <=
Age-upper limit
75 years-old >=
Gender Male and Female
Key inclusion criteria Type 2 diabetic patients who are treated with piogliitazone at least for 6 months and have good tolerance without relevant side effects
Key exclusion criteria Poor-controlled diabetes (HbA1c>8.0 %)
Target sample size 15

Research contact person
Name of lead principal investigator
1st name
Middle name
Last name Katsunori Ikewaki
Organization National Defense Medical College
Division name Department of Internal Medicine I
Zip code
Address 3-2 Namiki, Tokorozawa, JAPAN 359-8513
TEL 04-2995-1597
Email katsunorike@ndmc.ac.jp

Public contact
Name of contact person
1st name
Middle name
Last name Makoto Ayaori
Organization National Defense Medical College I
Division name Department of Internal Medicine
Zip code
Address 3-2 Namiki, Tokorozawa, JAPAN 359-8513
TEL 04-2995-1597
Homepage URL
Email ayaori@ndmc.ac.jp

Sponsor
Institute National Defense Medical College
Institute
Department

Funding Source
Organization Foundation for Promotion of Defense Medicine
Organization
Division
Category of Funding Organization Non profit foundation
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information
2010 Year 09 Month 15 Day

Related information
URL releasing protocol
Publication of results Published

Result
URL related to results and publications http://www.sciencedirect.com/science/article/pii/S0021915011007349
Number of participants that the trial has enrolled
Results
Objective
Pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist, reportedly reduces cardiovascular events in diabetic patients. ATP cassette binding transporters (ABC) A1 and G1 are pivotal molecules for cholesterol efflux (ChE) from macrophages and high density lipoprotein biogenesis, and the A1 transporter is regulated by a PPARgamma-liver receptor X (LXR) pathway. Also, pioglitazone induces ABCG1 expression, though the exact mechanism remains unclear. We therefore investigated the effects of pioglitazone on ABCA1/G1 expression in vitro and ex vivo.
Methods 
The effects of pioglitazone on ChE and ABCA1/G1 expressions inmacrophages were assessed. Then, mRNA was quantified in macrophages when PPARgamma/LXR inhibition by siRNA or overexpression of oxysterol sulfotransferase was performed. ABCA1/G1 promoter activity with mutated LXR-responsive elements was also measured. As an ex vivo study, 15 type 2 diabetic patients were administered pioglitazone or placebo, and ChE assays and protein expressions were determined using macrophages cultured with the corresponding sera.
Results
Pioglitazone increased LXRalpha/ABCA1/G1 expressions, which enhanced ChE from macrophages. Inhibition of PPARgamma/LXR pathways revealed that LXR was primarily involved in pioglitazone's transactivation of ABCA1 but only partially involved for ABCG1. Promoter assays showed that ABCG1 was regulated more by the promoter in intron 4 than that upstream of exon 1 but both promoters were responsive to LXR activation. Sera obtained after pioglitazone treatment promoted ChE and ABCA1/G1 expressions in macrophages.
Conclusion
Pioglitazone enhanced ChE from macrophages by increasing ABCA1/G1 in LXR-dependent and -independent manners. Our comparable in vitro and ex vivo results shed new light on pioglitazone's ovel anti-atherogenic property. 
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status Terminated
Date of protocol fixation
2010 Year 08 Month 10 Day
Date of IRB
Anticipated trial start date
2010 Year 09 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date
2010 Year 09 Month 10 Day
Last modified on
2013 Year 09 Month 12 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005033

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
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