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Telmisartan Promotes the Differentiation of Monocytes Into Macrophages M2 in Diabetic Nephropathy?

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ClinicalTrials.gov Identifier: NCT02768948
Recruitment Status : Unknown
Verified July 2018 by Centre Hospitalier Universitaire de Nice.
Recruitment status was:  Recruiting
First Posted : May 11, 2016
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Tracking Information
First Submitted Date  ICMJE May 10, 2016
First Posted Date  ICMJE May 11, 2016
Last Update Posted Date November 21, 2018
Actual Study Start Date  ICMJE May 5, 2017
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 10, 2016)
number of differentiation marker [ Time Frame: 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Telmisartan Promotes the Differentiation of Monocytes Into Macrophages M2 in Diabetic Nephropathy?
Official Title  ICMJE Telmisartan Promotes the Differentiation of Monocytes Into Macrophages M2 in Diabetic Nephropathy?
Brief Summary

The severity of the diabetic nephropathy is proportional to proteinuria rate and degree of renal interstitial fibrosis. Despite many treatments available today, diabetic nephropathy is responsible for a quarter of cases of end-stage renal disease (ESRD) requiring the use of renal replacement therapy or kidney transplantation. It develops as follows: chronic hyperglycemia of diabetes abyss renal glomeruli that allow proteins in the urine room. In response, the tubular epithelium produces monocyte chemoattractant protein-1 (MCP-1) that attracts monocytes circulating in the renal interstitium. Monocytes then differentiate into M1 or M2 macrophages. M1 macrophages increased MCP-1 production while M2 macrophages produce transforming growth factor beta (TGF-β) pro-fibrogenic. Renal fibrosis is negatively correlated with the glomerular filtration rate itself proportional to the number of nephrons. The decrease in the number of nephrons majorises secondarily proteinuria by the onset of focal segmental glomerulosclerosis lesions. Production of MCP-1 increases with the renal proteinuria because M1 macrophages earning kidneys reinforce the production of MCP-1, and fibrosis worsens because M2 macrophages infiltrate in turn kidneys and produce TGF -β.

A way of limiting renal fibrosis would be to decrease renal monocytic infiltration by promoting the differentiation of monocytes towards macrophages M2. Although more numerous, M2 macrophages no longer benefit the kidneys because the decline of M1 macrophages decrease renal MCP-1 production. Ex vivo IL1-β orients the differentiation of monocytes towards macrophages M1 and IL-4 to M2. By cons in vivo, the differentiating factors are poorly known. It is remarkable that metformin and telmisartan increase M2 macrophages M1 macrophages and decrease, respectively, in humans and mice. Moreover, telmisartan reduces proteinuria more than losartan in diabetic nephropathy in humans and Metformin decreases the amount of TGF-β intra-renal mice. This effect of telmisartan is independent of the type 1 receptor of angiotensin II (AT1R) since it is not obtained with losartan.

Telmisartan is a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma), the working assumption is that telmisartan fosters the transition of monocytes to macrophages M2 form, and limit the recruitment of more monocytes in the kidneys and therefore proteinuria and renal fibrosis. To show this, it will be compared the ability of monocytes to differentiate ex vivo in M1 or M2 macrophages in diabetic nephropathy patients treated with losartan or telmisartan then it will characterize the role of PPARgamma in the monocyte / macrophage transition. Finally, it will be compared the urinary excretion of amino terminal propeptide of procollagen type 3 (PIIINP), considered a marker of renal fibrosis in patients receiving losartan or telmisartan.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Diabetic Nephropathy
Intervention  ICMJE
  • Drug: telmisartan during 6 months
    telmisartan during 6 months
  • Drug: Losartan during 6 months
    Losartan during 6 months
  • Procedure: blood sample
    blood sample
Study Arms  ICMJE
  • Experimental: telmisartan
    treatment with telmisartan at doses of 80 mg / day for 6 months
    Interventions:
    • Drug: telmisartan during 6 months
    • Procedure: blood sample
  • Experimental: losartan
    Losartan at a dose of 100 mg / d for 6 months.
    Interventions:
    • Drug: Losartan during 6 months
    • Procedure: blood sample
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 10, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Type 2 diabetes ;
  • Proteinuria ≥ 0.5 g / g motivating the prescription of ACE inhibitors or ARA2 full dose;
  • Processing statin;
  • Processing metformin;
  • court treatment with GLP-1 agonists and DPP-4 inhibitor;
  • About who signed the informed consent;
  • affiliated to the social security issue

Exclusion Criteria:

  • Diabetic nephropathy not;
  • GFR <30 ml / min / 1.73 m2;
  • Type 1 diabetes;
  • Maturity Onset Diabetes of the Youth (MODY);
  • Use of telmisartan in the 6 months prior to enrollment;
  • Liver cirrhosis (potential production of PIIINP);
  • chronic inflammatory disease;
  • active cancer;
  • immunosuppression;
  • Pregnant or breastfeeding women (urine pregnancy test will be performed for women of childbearing age);
  • adult person under guardianship;
  • Hospitalized person without his consent and not protected by law; person deprived of liberty
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02768948
Other Study ID Numbers  ICMJE 16-AOI-09
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Centre Hospitalier Universitaire de Nice
Study Sponsor  ICMJE Centre Hospitalier Universitaire de Nice
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Centre Hospitalier Universitaire de Nice
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP