Angiotensin-II Receptor Antibodies Blockade With Losartan in Patients With Lupus Nephritis
Primary Purpose
Atherosclerosis, Lupus Nephritis
Status
Unknown status
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
Losartan
Enalapril
Sponsored by
About this trial
This is an interventional prevention trial for Atherosclerosis
Eligibility Criteria
Inclusion Criteria:
- Signed consent form for the study
- Biopsy-proven lupus nephritis with proteinuria > 1.5g/g by 24 hour urine protein to creatinine ratio
- Need for immunosuppressive induction to remission therapy according to the treatment physician
- Systemic lupus erythematosus diagnosis based on at least 4 American College of Rheumatology criteria
- Age between 16 and 50 years
Exclusion Criteria:
- Patient does not want to participate in the study
- Comorbid disease such as diabetes mellitus with macro/microangiopathy, previous diagnosis of hypertension >5 years, scleroderma
- Comorbid findings in the histopathological analysis of the renal biopsy
Sites / Locations
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Losartan
Enalapril
Arm Description
AT1R-ab effect can be blocked with the use of angiotensin-II receptor blockers. The participants will receive losartan.
Angiotensin converting enzyme inhibitors are indicated in the management of active lupus nephritis but do not block the effect of AT1R-Ab.
Outcomes
Primary Outcome Measures
Carotid intima-media thickness change after 12 months of the intervention
Change in carotid intima-media thickness from baseline thickness at study entry to 12 months of follow up measured by Doppler ultrasound
Secondary Outcome Measures
Response to treatment
Response to immunosuppressive treatment at 12 months
Arterial pressure
Arterial pressure control recorded by 24-hour ambulatory blood pressure
Full Information
NCT ID
NCT03526042
First Posted
April 16, 2018
Last Updated
May 14, 2018
Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators
National Council of Science and Technology, Mexico
1. Study Identification
Unique Protocol Identification Number
NCT03526042
Brief Title
Angiotensin-II Receptor Antibodies Blockade With Losartan in Patients With Lupus Nephritis
Official Title
Angiotensin-II Receptor Antibody Blockade With Losartan in Patients With Lupus Nephritis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
September 10, 2017 (Actual)
Primary Completion Date
July 31, 2019 (Anticipated)
Study Completion Date
October 31, 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Collaborators
National Council of Science and Technology, Mexico
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Antibodies directed against angiotensin-II receptor (AT1-Ab) are agonist antibodies previously studied in human diseases such as preeclampsia, transplantation and scleroderma. They act by binding to the AT1 receptor and their effects can be blocked with the use of angiotensin receptor blockers (ARB). In this randomized open clinical trial the investigators will study the effect of the blockade of AT1-Ab with losartan in carotid intima-media thickness progression in patients with lupus nephritis compared to patients treated with enalapril.
Detailed Description
Angiotensin-II type 1 receptor antibodies (AT1R-Ab) are agonist antibodies directed against the second loop of the AT1 receptor. These antibodies have been studied in human diseases such as preeclampsia, transplantation and scleroderma. A previous study from the investigators' group found an elevated prevalence of AT1R-Ab in patients with lupus nephritis. As these antibodies have been linked to atherosclerosis development this open randomized clinical trial was designed to evaluate the effect of AT1R-Ab blockade with losartan compared to the use of enalapril in the progression of carotid intima-media thickness (CIMT) in patients with active lupus nephritis.
Biopsy-proven lupus nephritis patients who tested positive for AT1R-Ab will be performed a CIMT measurement by Doppler ultrasound at the time of the biopsy and then at 12-months follow up.
The primary outcome will be the change in the CIMT in the course of 12 months in both groups.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerosis, Lupus Nephritis
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Open randomized clinical trial with parallel group comparing AT1R-ab blockade with losartan and enalapril as a control group.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Losartan
Arm Type
Experimental
Arm Description
AT1R-ab effect can be blocked with the use of angiotensin-II receptor blockers. The participants will receive losartan.
Arm Title
Enalapril
Arm Type
Active Comparator
Arm Description
Angiotensin converting enzyme inhibitors are indicated in the management of active lupus nephritis but do not block the effect of AT1R-Ab.
Intervention Type
Drug
Intervention Name(s)
Losartan
Other Intervention Name(s)
Angiotensin receptor blocker
Intervention Description
Competitive blockade of AT1R-antibodies effect by binding to the angiotensin 1 receptor
Intervention Type
Drug
Intervention Name(s)
Enalapril
Other Intervention Name(s)
Angiotensin Converting Enzyme Inhibitor
Intervention Description
Renin-angiotensin-aldosterone system (RAAS) blockade without any effect on AT1R-antibodies effect or concentration (control group)
Primary Outcome Measure Information:
Title
Carotid intima-media thickness change after 12 months of the intervention
Description
Change in carotid intima-media thickness from baseline thickness at study entry to 12 months of follow up measured by Doppler ultrasound
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Response to treatment
Description
Response to immunosuppressive treatment at 12 months
Time Frame
12 months
Title
Arterial pressure
Description
Arterial pressure control recorded by 24-hour ambulatory blood pressure
Time Frame
12months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed consent form for the study
Biopsy-proven lupus nephritis with proteinuria > 1.5g/g by 24 hour urine protein to creatinine ratio
Need for immunosuppressive induction to remission therapy according to the treatment physician
Systemic lupus erythematosus diagnosis based on at least 4 American College of Rheumatology criteria
Age between 16 and 50 years
Exclusion Criteria:
Patient does not want to participate in the study
Comorbid disease such as diabetes mellitus with macro/microangiopathy, previous diagnosis of hypertension >5 years, scleroderma
Comorbid findings in the histopathological analysis of the renal biopsy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Luis E Morales-Buenrostro, PhD
Phone
54870900
Ext
4142
Email
luis_buenrostro@yahoo.com.mx
First Name & Middle Initial & Last Name or Official Title & Degree
Juan M Mejia-Vilet, MD,MSc
Phone
54870900
Ext
4142
Email
jmmejia@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luis E Morales-Buenrostro, PhD
Organizational Affiliation
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
City
Mexico City
ZIP/Postal Code
14080
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan M Mejia-Vilet, MD,MSc
Phone
54870900
Ext
4142
Email
jmmejia@hotmail.com
First Name & Middle Initial & Last Name & Degree
Luis E Morales-Buenrostro, PhD
Phone
54870900
Ext
4142
Email
luis_buenrostro@yahoo.com.mx
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Angiotensin-II Receptor Antibodies Blockade With Losartan in Patients With Lupus Nephritis
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