Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03260452
Recruitment Status : Completed
First Posted : August 24, 2017
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Toulouse

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.

Condition or disease Intervention/treatment Phase
Type2 Diabetes Procedure: Abdominal subcutaneous biopsies and Blood test Not Applicable

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention 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.
Primary Purpose: Basic Science
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
Actual Study Start Date : June 28, 2018
Actual Primary Completion Date : January 24, 2019
Actual Study Completion Date : January 24, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy

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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Comparison of hematopoietic activity in vitro between both groups of subjects. [ Time Frame: Day 3 - Day 45 ]
    Evaluated by flow cytometry.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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).

  7. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   37 Years to 63 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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).

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): NCT03260452


Locations
Layout table for location information
France
CHU de Toulouse - Rangueil
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
Investigators
Layout table for investigator information
Principal Investigator: Pierre GOURDY CHU Toulouse

Publications:

Layout table for additonal information
Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT03260452     History of Changes
Other Study ID Numbers: RC31/15/7739
2017-A01697-46 ( Other Identifier: ID-RCB )
First Posted: August 24, 2017    Key Record Dates
Last Update Posted: April 2, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Toulouse:
Type 2 diabetes
Adipose tissue
Hematopoiesis
Inflammation
Macrophages

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