Angiotensin-II Receptor Antibodies Blockade With Losartan in Patients With Lupus Nephritis

Not Applicable

• Conditions: Atherosclerosis; Lupus Nephritis
• Interventions: Drug: Losartan; Drug: Enalapril

• Registration Number: NCT03526042
• Lead Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

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.

Study Timeline

• Study Start: 2017-09-10
• Study First Submitted: 2018-04-16
• Status Verified: 2018-05
• Study First Submitted QC: 2018-05-14
• Last Update Submitted: 2018-05-14
• Study First Posted: 2018-05-16
• Last Update Posted: 2018-05-16
• Primary Completion: 2019-07-31
• Study Completion: 2019-10-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Losartan	Losartan	AT1R-ab effect can be blocked with the use of angiotensin-II receptor blockers. The participants will receive losartan.
Enalapril	Enalapril	Angiotensin converting enzyme inhibitors are indicated in the management of active lupus nephritis but do not block the effect of AT1R-Ab.

Primary Outcome Measures

Name	Time	Method
Carotid intima-media thickness change after 12 months of the intervention	12 months	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

Name	Time	Method
Response to treatment	12 months	Response to immunosuppressive treatment at 12 months
Arterial pressure	12months	Arterial pressure control recorded by 24-hour ambulatory blood pressure

Trial Locations

Locations (1)

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran; 🇲🇽 Mexico City, Mexico