Comparison of Hematopoietic Stem Cell Activity in Adipose Tissue From Type 2 Diabetic Patients and Healthy Volunteers (WAT2DO)
2019年4月1日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
20
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Toulouse、フランス、31059
- CHU de Toulouse - Rangueil
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
37年～63年 (大人)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
男
説明
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).
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：Patients
'Abdominal subcutaneous biopsies and Blood test'
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Abdominal subcutaneous biopsies and blood test for each volunteer.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of pro-inflammatory macrophages derived from human adipose tissue in mice transplanted with adipose tissue-hematopoietic stem cells .
時間枠：Day 3 - Day 45
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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.
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Day 3 - Day 45
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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Comparison of hematopoietic activity in vitro between both groups of subjects.
時間枠：Day 3 - Day 45
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Evaluated by flow cytometry.
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Day 3 - Day 45
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Comparison of the number of the other cell types derived from the human adipose tissue-hematopoietic stem cells between both groups of grafted mice.
時間枠：Day 3 - Day 45
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Evaluated by flow cytometry.
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Day 3 - Day 45
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Comparison of the phenotype of the other cell types derived from the human adipose tissue-hematopoietic stem cells between both groups of grafted mice.
時間枠：Day 3 - Day 45
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Evaluated by flow cytometry.
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Day 3 - Day 45
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Comparison of the expression of genes coding for human inflammatory molecules in the adipose tissue of transplanted mice.
時間枠：Day 3 - Day 45
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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.
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Day 3 - Day 45
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Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's glycemia.
時間枠：Day 3 - Day 45
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According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).
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Day 3 - Day 45
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Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's insulinemia.
時間枠：Day 3 - Day 45
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According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).
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Day 3 - Day 45
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Comparison of the metabolic profile of the transplanted mice evaluated by the grafted mice's oral glucose tolerance test.
時間枠：Day 3 - Day 45
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According to the origin of the grafted hematopoietic stem cells (diabetic or healthy voluntary subjects).
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Day 3 - Day 45
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Pierre GOURDY、Chu Toulouse
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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. Erratum In: J Physiol Biochem. 2011 Sep;67(3):497. Castiella, L [corrected to Casteilla, L].
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2018年6月28日
一次修了 (実際)
2019年1月24日
研究の完了 (実際)
2019年1月24日
試験登録日
最初に提出
2017年7月27日
QC基準を満たした最初の提出物
2017年8月21日
最初の投稿 (実際)
2017年8月24日
学習記録の更新
投稿された最後の更新 (実際)
2019年4月2日
QC基準を満たした最後の更新が送信されました
2019年4月1日
最終確認日
2019年4月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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