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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02286128
• Other study ID #: ChiangMaiU
• Status: Completed
• Start date: November 2014
• Est. completion date: May 3, 2018

Study information

• Verified date: July 2018
• Source: Chiang Mai University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: May 3, 2018
• Est. primary completion date: May 3, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Locations

Country	Name	City	State
Thailand	Mattabhorn Phornputkul	Chiang Mai

Sponsors (1)

Lead Sponsor	Collaborator
Chiang Mai University

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation between NF-?B dependent-proinflammation markers and osteoblast-specific gene expression in the MSC to measure the effects of NF-?B dependent-proinflammation on differentiation potential toward osteoblast in type 2 diabetes.		2-4 weeks
Secondary	Correlation between NF-?B dependent-proinflammation markers and apoptotic marker expression in the MSC to measure effects of NF-?B dependent-proinflammation on cellular apoptosis in type 2 diabetes.		2-4 weeks
Secondary	Correlation between NF-?B dependent-proinflammation markers and the expression of RAGE and its downstream signals in the MSC to measure effects of NF-?B dependent-proinflammation on cellular RAGE activation in type 2 diabetes.		2-4 weeks