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Comparison of Hematopoietic Stem Cell Activity in Adipose Tissue From Type 2 Diabetic Patients and Healthy Volunteers (WAT2DO)

Primary Purpose

Type2 Diabetes

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Abdominal subcutaneous biopsies and Blood test

About this trial

This is an interventional basic science trial for Type2 Diabetes focused on measuring Type 2 diabetes, Adipose tissue, Hematopoiesis, Inflammation, Macrophages

Eligibility Criteria

37 Years - 63 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

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).
40 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).
37 to 63 year-old, age-matched to a type 2 diabetes subject ± 5 years.
Fasting blood glucose < 1,10 g / L.
HbA1c within normal limits (4 to 6%).

Exclusion Criteria:

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.
Hypertriglyceridemia > 2.5 g / l
Person under the protection of justice, guardianship or curators.
Subject involved in another research protocol or in an exclusion period from another research protocol.
Cognitive disorder or mental pathology (at the discretion of the investigator).

Sites / Locations

CHU de Toulouse - Rangueil

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients

Arm Description

'Abdominal subcutaneous biopsies and Blood test'

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Evaluated by flow cytometry.

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

Evaluated by flow cytometry.

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

Evaluated by flow cytometry.

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

Evaluated by Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction. Main parameters analysed : Interleukin-6, Interleukin-1béta, Plasminogen activator inhibitor-1, Monocyte Chemoattractant Protein-1.

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

According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).

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

According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).

Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's oral glucose tolerance test.

According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).

Full Information

NCT ID

NCT03260452

First Posted

July 27, 2017

Last Updated

April 1, 2019

Sponsor

University Hospital, Toulouse

1. Study Identification

Unique Protocol Identification Number

NCT03260452

Brief Title

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

Acronym

WAT2DO

Official Title

Comparison of Hematopoietic Stem Cell Activity in Adipose Tissue From Type 2 Diabetic Patients and Healthy Volunteers: Proof of Concept Study. White Adipose Tissue and Type 2 Diabetes Onset: WAT2DO

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

June 28, 2018 (Actual)

Primary Completion Date

January 24, 2019 (Actual)

Study Completion Date

January 24, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Toulouse

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

In mice, increasing data demonstrate a causal relationship between the inflammatory process in adipose tissue and the development of insulin resistance, resulting in type 2 diabetes occurrence. However, the mechanisms mediating inflammation and its metabolic consequences are still unclear. In humans, recent publications have suggested an important interaction between the metabolic status and medullar hematopoietic activity. A preliminary study performed by the STROMAlab's research team has identified functional hematopoietic stem cells in human adipose tissue samples, indicating that adipose tissue-hematopoiesis is an active mechanism. To determine whether an alteration in adipose tissue-hematopoiesis could be a hallmark of type 2 diabetes in human, biopsies of subcutaneous adipose tissue will be performed in 2 groups of 10 volunteers: overweight/obese type 2 diabetes subjects versus healthy volunteers, matched on age. Then, hematopoietic stem cells extracted from human biopsies will be grafted into immunodeficient mice and after 12 weeks, flow cytometry using antibodies specific for human cell surface markers will be performed to quantify proinflammatory macrophages derived from human adipose tissue-hematopoietic stem cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type2 Diabetes

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Model Description

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

Masking

None (Open Label)

Masking Description

All laboratory analyses will be performed blindly.

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patients

Arm Type

Experimental

Arm Description

'Abdominal subcutaneous biopsies and Blood test'

Intervention Type

Procedure

Intervention Name(s)

Abdominal subcutaneous biopsies and Blood test

Intervention Description

Abdominal subcutaneous biopsies and blood test for each volunteer.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Day 3 - Day 45

Secondary Outcome Measure Information:

Title

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

Description

Evaluated by flow cytometry.

Time Frame

Day 3 - Day 45

Title

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

Description

Evaluated by flow cytometry.

Time Frame

Day 3 - Day 45

Title

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

Description

Evaluated by flow cytometry.

Time Frame

Day 3 - Day 45

Title

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

Description

Time Frame

Day 3 - Day 45

Title

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

Description

According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).

Time Frame

Day 3 - Day 45

Title

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

Description

According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).

Time Frame

Day 3 - Day 45

Title

Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's oral glucose tolerance test.

Description

According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).

Time Frame

Day 3 - Day 45

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

37 Years

Maximum Age & Unit of Time

63 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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). 40 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). 37 to 63 year-old, age-matched to a type 2 diabetes subject ± 5 years. Fasting blood glucose < 1,10 g / L. HbA1c within normal limits (4 to 6%). Exclusion Criteria: 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. Hypertriglyceridemia > 2.5 g / l Person under the protection of justice, guardianship or curators. Subject involved in another research protocol or in an exclusion period from another research protocol. Cognitive disorder or mental pathology (at the discretion of the investigator).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pierre GOURDY

Organizational Affiliation

CHU Toulouse

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHU de Toulouse - Rangueil

City

Toulouse

ZIP/Postal Code

31059

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Citations:

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

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