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

April 1, 2019 updated by: University Hospital, Toulouse

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

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

  • France
      • Toulouse, France, 31059
        • CHU de Toulouse - Rangueil

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

37 years to 63 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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).

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

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Patients
'Abdominal subcutaneous biopsies and Blood test'
Procedure: Abdominal subcutaneous biopsies and Blood test
Abdominal subcutaneous biopsies and blood test for each volunteer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of pro-inflammatory macrophages derived from human adipose tissue in mice transplanted with adipose tissue-hematopoietic stem cells .
Time Frame: Day 3 - Day 45
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of hematopoietic activity in vitro between both groups of subjects.
Time Frame: Day 3 - Day 45
Evaluated by flow cytometry.
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.
Time Frame: Day 3 - Day 45
Evaluated by flow cytometry.
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.
Time Frame: Day 3 - Day 45
Evaluated by flow cytometry.
Day 3 - Day 45
Comparison of the expression of genes coding for human inflammatory molecules in the adipose tissue of transplanted mice.
Time Frame: Day 3 - Day 45
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.
Day 3 - Day 45
Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's glycemia.
Time Frame: Day 3 - Day 45
According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).
Day 3 - Day 45
Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's insulinemia.
Time Frame: Day 3 - Day 45
According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).
Day 3 - Day 45
Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's oral glucose tolerance test.
Time Frame: Day 3 - Day 45
According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).
Day 3 - Day 45

Collaborators and Investigators

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

Sponsor

University Hospital, Toulouse

Investigators

  • Principal Investigator: Pierre GOURDY, CHU Toulouse

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

June 28, 2018

Primary Completion (Actual)

January 24, 2019

Study Completion (Actual)

January 24, 2019

Study Registration Dates

First Submitted

July 27, 2017

First Submitted That Met QC Criteria

August 21, 2017

First Posted (Actual)

August 24, 2017

Study Record Updates

Last Update Posted (Actual)

April 2, 2019

Last Update Submitted That Met QC Criteria

April 1, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC31/15/7739
  • 2017-A01697-46 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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