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

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ClinicalTrials.gov Identifier: NCT02286128
Recruitment Status : Active, not recruiting
First Posted : November 7, 2014
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
Mattabhorn Phornphutkul, Chiang Mai University

Brief 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.

Condition or disease
Type 2 Diabetes

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
Actual Enrollment : 75 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
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
Actual Study Start Date : November 2014
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : May 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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



Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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. 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 ]

Biospecimen Retention:   Samples Without DNA
Serum and RNA (from peripheral blood-derived mesenchymal stem cells)


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02286128


Locations
Thailand
Mattabhorn Phornputkul
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Chiang Mai University
Investigators
Principal Investigator: Mattabhorn Phornphutkul, M.D, Ph.D Chiang Mai University

Responsible Party: Mattabhorn Phornphutkul, Assistant Professor, Chiang Mai University
ClinicalTrials.gov Identifier: NCT02286128     History of Changes
Other Study ID Numbers: ChiangMaiU
First Posted: November 7, 2014    Key Record Dates
Last Update Posted: March 27, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Mattabhorn Phornphutkul, Chiang Mai University:
Type 2 diabetes
RAGE
osteoblast

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases