Diabetic NephropathyNCT02768948
Telmisartan Promotes the Differentiation of Monocytes Into Macrophages M2 in Diabetic Nephropathy?
A study testing telmisartan during 6 months, Losartan during 6 months and blood sample in people with Diabetic Nephropathy, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Nephropathy
- What is being tested?
- telmisartan during 6 months, Losartan during 6 months and blood sample
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 5 May 2017to 11 Jul 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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);
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Diabetic Nephropathy
- Being tested
- telmisartan during 6 months, Losartan during 6 months, blood sample
- Medical subject headings
- Diabetic Nephropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
telmisartan during 6 monthsDrug
telmisartan during 6 months
Losartan during 6 monthsDrug
Losartan during 6 months
blood sampleProcedure or surgery
blood sample
| Study group | Role | What they receive |
|---|---|---|
| telmisartan | Experimental | treatment with telmisartan at doses of 80 mg / day for 6 months Receives: Drug: telmisartan during 6 months; Procedure: blood sample |
| losartan | Experimental | Losartan at a dose of 100 mg / d for 6 months. Receives: Drug: Losartan during 6 months; Procedure: blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of differentiation marker
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2016 (estimated)
- Study start5 May 2017
- Primary completion11 Sep 2019
- Study completion11 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic NephropathyStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02768948
- Sponsor's protocol ID
- 16-AOI-09
- Status last verified
- May 2022
- First submitted
- 10 May 2016
- Last updated
- 19 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Telmisartan Promotes the Differentiation of Monocytes Into Macrophages M2 in Diabetic Nephropathy?
- ClinicalTrials.gov ID
- NCT02768948
- Acronym / sponsor ID
- 16-AOI-09
- Conditions
- Diabetic Nephropathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 5 May 2017 (actual)
- Primary completion
- 11 Sep 2019 (actual)
- Study completion
- 11 Jul 2020 (actual)
- First posted
- 11 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| telmisartan | Experimental | Drug: telmisartan during 6 months, Procedure: blood sampletreatment with telmisartan at doses of 80 mg / day for 6 months |
| losartan | Experimental | Drug: Losartan during 6 months, Procedure: blood sampleLosartan at a dose of 100 mg / d for 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| telmisartan during 6 monthstelmisartan during 6 months | Drug | telmisartan |
| Losartan during 6 monthsLosartan during 6 months | Drug | losartan |
| blood sampleblood sample | Procedure or surgery | losartan, telmisartan |
Primary outcome
number of differentiation marker
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing telmisartan during 6 months, Losartan during 6 months and blood sample in people with Diabetic Nephropathy, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of differentiation marker (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2022.