Effect of NF-кB Dependent Proinflammation on Osteogenic Differentiation of the Mesenchymal Stem Cells in Type 2 Diabetes

July 11, 2018 updated by: Mattabhorn Phornphutkul, Chiang Mai University

The Effect of NF-кB Dependent Proinflammation on the Overexpression of Receptor of Advanced Glycation End Products (RAGE) and the Osteogenic Differentiation Defect in the Mesenchymal Stem Cell-isolated From Patients With Type 2 Diabetes

This study determines whether NF-кB dependent proinflammatory state found in type 2 diabetes yield to a higher RAGE activation in the mesenchymal stem cell, as well as the effects of the proinflammation on osteoblast differentiation impairment and cellular apoptosis in type 2 diabetic patients. This study will compare non-diabetic control subjects and type 2 diabetic patients with metformin monotherapy failure in the aspect of 1) serum markers for NF-кB dependent proinflammatory state and its intracellular signals, 2) osteogenic differentiation and apoptosis of the mesenchymal stem cells, and 3) serum AGE, RAGE and cellular RAGE activation.

Study Overview

Status

Completed

Conditions

Detailed Description

This study aims to explore whether proinflammation in type 2 diabetes is an mechanism underlined higher RAGE activation and osteoblast differentiation defect demonstrated in the MSC of type 2 diabetes, as well as the effects of the proinflammation on cellular differentiation and apoptosis of the MSC. Type 2 diabetes was known to be in proinflammatory state due to NF-кB-dependent cytokine secretion (for example, TNF-α, IL1 and IL6), which in turn contribute to NF-кB upregulation. Because RAGE expression is partly regulated by NF-кB signal, the NF-кB upregulation in proinflammatory state observed in type 2 diabetes may entail RAGE overactivation in this population. Therefore, the proinflammatory state and its correlation to cellular NF-кB-dependent RAGE activation is noteworthy to be determined in the MSC of type 2 diabetes. Furthermore, the effect of proinflammation on differentiation potential and apoptosis of the MSC in type 2 diabetes remains to be elucidated.

Study Type

Observational

Enrollment (Actual)

75

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Chiang Mai, Thailand, 50200
        • Mattabhorn Phornputkul

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

This study will include 30 non-diabetic control subjects, and 45 type 2 diabetic patients who has HbA1c higher than 6.5% with metformin monotherapy.

Description

Inclusion Criteria:

  • Patients with type 2 diabetes who has HbA1c higher than 6.5% with metformin monotherapy and age-matched non-diabetes control subjects who signed consent form to be in the study.

Exclusion Criteria:

  • Patients who use thiazolidinedione, steroid, immunosuppressive medications, antiresorptive agents or anabolic therapy for osteoporosis.
  • Patients with elevated serum creatinine higher than 1.4 in female and 1.5 in male.
  • Patients with metastases cancer or hematologic malignancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Non-diabetic controls
Age-matched non-diabetic subjects
Type 2 diabetes
Type 2 diabetes with metformin monotherapy failure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Correlation between NF-кB dependent-proinflammation markers and osteoblast-specific gene expression in the MSC to measure the effects of NF-кB dependent-proinflammation on differentiation potential toward osteoblast in type 2 diabetes.
Time Frame: 2-4 weeks
2-4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Correlation between NF-кB dependent-proinflammation markers and apoptotic marker expression in the MSC to measure effects of NF-кB dependent-proinflammation on cellular apoptosis in type 2 diabetes.
Time Frame: 2-4 weeks
2-4 weeks
Correlation between NF-кB dependent-proinflammation markers and the expression of RAGE and its downstream signals in the MSC to measure effects of NF-кB dependent-proinflammation on cellular RAGE activation in type 2 diabetes.
Time Frame: 2-4 weeks
2-4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chiang Mai University

Investigators

  • Principal Investigator: Mattabhorn Phornphutkul, M.D, Ph.D, Chiang Mai University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2014

Primary Completion (Actual)

May 3, 2018

Study Completion (Actual)

May 3, 2018

Study Registration Dates

First Submitted

October 28, 2014

First Submitted That Met QC Criteria

November 5, 2014

First Posted (Estimate)

November 7, 2014

Study Record Updates

Last Update Posted (Actual)

July 12, 2018

Last Update Submitted That Met QC Criteria

July 11, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ChiangMaiU

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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