Comparison of Hematopoietic Stem Cell Activity in Adipose Tissue From Type 2 Diabetic Patients and Healthy Volunteers

NCT03260452 | Completed

• 2 other identifiers: RC31/15/77392017-A01697-46
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Based on solid preclinical results in mice and preliminary data in humans, this study aims to provide the proof of concept of the crucial role of the hematopoietic process occurring in human adipose tissue in the initiation of the inflammatory process at the origin of insulin resistance and type 2 diabetes (T2D). The main objective is to compare the number of pro-inflammatory macrophages derived from human adipose tissue hematopoietic stem cells (HSC) according to their origin, type 2 diabetes subjects or healthy volunteers.

Conditions

Type2 Diabetes

Keywords

Type 2 diabetes; Adipose tissue; Hematopoiesis; Inflammation; Macrophages

Outcome Measures

Primary Outcomes (1)

• Number of pro-inflammatory macrophages derived from human adipose tissue in mice transplanted with adipose tissue-hematopoietic stem cells .

  The investigators expect that the number of pro-inflammatory macrophages derived from human adipose tissue will be significantly higher in mice transplanted with adipose tissue-hematopoietic stem cells isolated from diabetic subjects compared to those from healthy volunteers.

  Day 3 - Day 45

Secondary Outcomes (7)

• Comparison of hematopoietic activity in vitro between both groups of subjects.

  Day 3 - Day 45

• Comparison of the number of the other cell types derived from the human adipose tissue-hematopoietic stem cells between both groups of grafted mice.

  Day 3 - Day 45

• Comparison of the phenotype of the other cell types derived from the human adipose tissue-hematopoietic stem cells between both groups of grafted mice.

  Day 3 - Day 45

• Comparison of the expression of genes coding for human inflammatory molecules in the adipose tissue of transplanted mice.

  Day 3 - Day 45

• Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's glycemia.

  Day 3 - Day 45

Study Arms (1)

Patients

EXPERIMENTAL

'Abdominal subcutaneous biopsies and Blood test'

Procedure: Abdominal subcutaneous biopsies and Blood test

Interventions

Abdominal subcutaneous biopsies and Blood test PROCEDURE

Abdominal subcutaneous biopsies and blood test for each volunteer.

Patients

Eligibility Criteria

• Age: 37 Years - 63 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• No major weight variation for at least 3 months
• Biological assessment without clinically significant anomaly from the point of view of the investigator.
• Acceptance of constraints related to participation in the study
• Acceptance of participation in the constitution of a cell bank, a tissue bank and a serum library.
• Affiliation to a social security scheme.
• Type 2 diabetic subjects:
• Type 2 diabetes (discovered after the age of 35 years, without inaugural ketosis and absence of insulin therapy during the first year).
• to 60 year-old.
• BMI between 27 and 35 kg / m² (included).
• Treated by modification of lifestyle alone or associated to oral anti-diabetic therapy only.
• With stable oral anti-diabetic treatment for at least 3 months.
• HbA1c ≤ 8.5%.
• Healthy Volunteers:
• BMI between 23 and 27 kg / m² (included).
• to 63 year-old, age-matched to a type 2 diabetes subject ± 5 years.

You may not qualify if:

• Excessive chronic alcohol consumption (\> 30 g / day or 210 g / week).
• Tobacco consumption\> 10 cigarettes / day that cannot be stopped for 24 hours.
• Anti-diabetic treatments that require sub-cutaneous injections
• History of chronic or acute hematological pathology.
• Systemic or acute inflammatory pathology.
• Treatment with antiplatelet agents, non-steroidal anti-inflammatory drugs, glucocorticoids (excluding eye drops and sprays), or other immunosuppressive drugs.
• History of cancer (except basal cell carcinoma).
• Allergy to xylocaine or one of its derivatives.
• Any significant pathology at the discretion of the investigator.
• Any biological anomaly at the discretion of the investigator.
• Positive human immunodeficiency virus serology.
• Positive hepatitis B serology.
• Positive hepatitis C serology.
• Glomerular filtration rate less than 60 ml / min
• Aspartate aminotransferase or alanine aminotransferase higher than 2.5-fold the upper normal value.

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

CHU de Toulouse - Rangueil

Toulouse, 31059, France

Location

Related Publications (19)

• Casteilla L, Planat-Benard V, Laharrague P, Cousin B. Adipose-derived stromal cells: Their identity and uses in clinical trials, an update. World J Stem Cells. 2011 Apr 26;3(4):25-33. doi: 10.4252/wjsc.v3.i4.25.

  PMID: 21607134 BACKGROUND

• Bour S, Caspar-Bauguil S, Iffiu-Soltesz Z, Nibbelink M, Cousin B, Miiluniemi M, Salmi M, Stolen C, Jalkanen S, Casteilla L, Penicaud L, Valet P, Carpene C. Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition. Am J Pathol. 2009 Mar;174(3):1075-83. doi: 10.2353/ajpath.2009.080612. Epub 2009 Feb 13.

  PMID: 19218346 BACKGROUND

• Brooks-Worrell B, Narla R, Palmer JP. Biomarkers and immune-modulating therapies for type 2 diabetes. Trends Immunol. 2012 Nov;33(11):546-53. doi: 10.1016/j.it.2012.07.002. Epub 2012 Aug 14.

  PMID: 22897868 BACKGROUND

• Cancello R, Clement K. Is obesity an inflammatory illness? Role of low-grade inflammation and macrophage infiltration in human white adipose tissue. BJOG. 2006 Oct;113(10):1141-7. doi: 10.1111/j.1471-0528.2006.01004.x. Epub 2006 Aug 10.

  PMID: 16903845 BACKGROUND

• Caspar-Bauguil S, Cousin B, Bour S, Casteilla L, Penicaud L, Carpene C. Adipose tissue lymphocytes: types and roles. J Physiol Biochem. 2009 Dec;65(4):423-36. doi: 10.1007/BF03185938.

  PMID: 20358356 BACKGROUND

• Cousin B, Andre M, Arnaud E, Penicaud L, Casteilla L. Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochem Biophys Res Commun. 2003 Feb 21;301(4):1016-22. doi: 10.1016/s0006-291x(03)00061-5.

  PMID: 12589814 BACKGROUND

• Dalmas E, Tordjman J, Guerre-Millo M, Clement K. [Adipose tissue, a new playground for immune cells]. Med Sci (Paris). 2011 Nov;27(11):993-9. doi: 10.1051/medsci/20112711016. Epub 2011 Nov 30. French.

  PMID: 22130027 BACKGROUND

• Han J, Koh YJ, Moon HR, Ryoo HG, Cho CH, Kim I, Koh GY. Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood. 2010 Feb 4;115(5):957-64. doi: 10.1182/blood-2009-05-219923. Epub 2009 Nov 6.

  PMID: 19897586 BACKGROUND

• Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, Miller RG, Ramkhelawon B, Distel E, Westerterp M, Huang LS, Schmidt AM, Orchard TJ, Fisher EA, Tall AR, Goldberg IJ. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. 2013 May 7;17(5):695-708. doi: 10.1016/j.cmet.2013.04.001.

  PMID: 23663738 BACKGROUND

• Nikolajczyk BS, Jagannathan-Bogdan M, Denis GV. The outliers become a stampede as immunometabolism reaches a tipping point. Immunol Rev. 2012 Sep;249(1):253-75. doi: 10.1111/j.1600-065X.2012.01142.x.

  PMID: 22889227 BACKGROUND

• Poglio S, De Toni-Costes F, Arnaud E, Laharrague P, Espinosa E, Casteilla L, Cousin B. Adipose tissue as a dedicated reservoir of functional mast cell progenitors. Stem Cells. 2010 Nov;28(11):2065-72. doi: 10.1002/stem.523.

  PMID: 20845475 BACKGROUND

• Poglio S, De Toni F, Lewandowski D, Minot A, Arnaud E, Barroca V, Laharrague P, Casteilla L, Cousin B. In situ production of innate immune cells in murine white adipose tissue. Blood. 2012 Dec 13;120(25):4952-62. doi: 10.1182/blood-2012-01-406959. Epub 2012 Oct 15.

  PMID: 23071275 BACKGROUND

• Prunet-Marcassus B, Cousin B, Caton D, Andre M, Penicaud L, Casteilla L. From heterogeneity to plasticity in adipose tissues: site-specific differences. Exp Cell Res. 2006 Apr 1;312(6):727-36. doi: 10.1016/j.yexcr.2005.11.021. Epub 2005 Dec 28.

  PMID: 16386732 BACKGROUND

• Richardson VR, Smith KA, Carter AM. Adipose tissue inflammation: feeding the development of type 2 diabetes mellitus. Immunobiology. 2013 Dec;218(12):1497-504. doi: 10.1016/j.imbio.2013.05.002. Epub 2013 May 16.

  PMID: 23816302 BACKGROUND

• Shapiro H, Lutaty A, Ariel A. Macrophages, meta-inflammation, and immuno-metabolism. ScientificWorldJournal. 2011;11:2509-29. doi: 10.1100/2011/397971. Epub 2011 Dec 28.

  PMID: 22235182 BACKGROUND

• Spinetti G, Cordella D, Fortunato O, Sangalli E, Losa S, Gotti A, Carnelli F, Rosa F, Riboldi S, Sessa F, Avolio E, Beltrami AP, Emanueli C, Madeddu P. Global remodeling of the vascular stem cell niche in bone marrow of diabetic patients: implication of the microRNA-155/FOXO3a signaling pathway. Circ Res. 2013 Feb 1;112(3):510-22. doi: 10.1161/CIRCRESAHA.112.300598. Epub 2012 Dec 18.

  PMID: 23250986 BACKGROUND

• Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003 Dec;112(12):1796-808. doi: 10.1172/JCI19246.

  PMID: 14679176 BACKGROUND

• Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003 Dec;112(12):1821-30. doi: 10.1172/JCI19451.

  PMID: 14679177 BACKGROUND

• Ito R, Takahashi T, Katano I, Ito M. Current advances in humanized mouse models. Cell Mol Immunol. 2012 May;9(3):208-14. doi: 10.1038/cmi.2012.2. Epub 2012 Feb 13.

  PMID: 22327211 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Inflammation

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Pierre GOURDY

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: All laboratory analyses will be performed blindly.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 20 male volunteers: 10 overweight/obese subjects with T2D and 10 healthy volunteers, age-matched. All volunteers will be treated in the same way.

Study Record Dates

• First Submitted: July 27, 2017
• First Posted: August 24, 2017
• Study Start: June 28, 2018
• Primary Completion: January 24, 2019
• Study Completion: January 24, 2019
• Last Updated: April 2, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)