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

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (Other)

Overall Status

Unknown status

CT.gov ID

NCT03526042

Collaborator

National Council of Science and Technology, Mexico (Other)

Enrollment

Location

Arms

25.7

Anticipated Duration (Months)

1.6

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis Lupus Nephritis	Drug: Losartan Drug: Enalapril	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Open randomized clinical trial with parallel group comparing AT1R-ab blockade with losartan and enalapril as a control group.Open randomized clinical trial with parallel group comparing AT1R-ab blockade with losartan and enalapril as a control group.

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Sep 10, 2017

Anticipated Primary Completion Date :

Jul 31, 2019

Anticipated Study Completion Date :

Oct 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Losartan AT1R-ab effect can be blocked with the use of angiotensin-II receptor blockers. The participants will receive losartan.	Drug: Losartan Competitive blockade of AT1R-antibodies effect by binding to the angiotensin 1 receptor Other Names: Angiotensin receptor blocker
Active Comparator: Enalapril Angiotensin converting enzyme inhibitors are indicated in the management of active lupus nephritis but do not block the effect of AT1R-Ab.	Drug: Enalapril Renin-angiotensin-aldosterone system (RAAS) blockade without any effect on AT1R-antibodies effect or concentration (control group) Other Names: Angiotensin Converting Enzyme Inhibitor

Arm

Intervention/Treatment

Experimental: Losartan

AT1R-ab effect can be blocked with the use of angiotensin-II receptor blockers. The participants will receive losartan.

Drug: Losartan

Competitive blockade of AT1R-antibodies effect by binding to the angiotensin 1 receptor

Other Names:

Angiotensin receptor blocker

Active Comparator: Enalapril

Angiotensin converting enzyme inhibitors are indicated in the management of active lupus nephritis but do not block the effect of AT1R-Ab.

Drug: Enalapril

Renin-angiotensin-aldosterone system (RAAS) blockade without any effect on AT1R-antibodies effect or concentration (control group)

Other Names:

Angiotensin Converting Enzyme Inhibitor

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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