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

Atherosclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03526042
• Other study ID #: NMM-1816,16/16-1
• Status: Recruiting
• Phase: N/A
• Start date: September 10, 2017
• Est. completion date: October 31, 2019

Study information

• Verified date: May 2018
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: Luis E Morales-Buenrostro, PhD
• Phone: 54870900
• Email: luis_buenrostro[@]yahoo.com.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 31, 2019
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Lupus Nephritis
• Nephritis

Intervention

Drug:
• Losartan
Competitive blockade of AT1R-antibodies effect by binding to the angiotensin 1 receptor
• Enalapril
Renin-angiotensin-aldosterone system (RAAS) blockade without any effect on AT1R-antibodies effect or concentration (control group)

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	National Council of Science and Technology, Mexico

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	12 months
Secondary	Response to treatment	Response to immunosuppressive treatment at 12 months	12 months
Secondary	Arterial pressure	Arterial pressure control recorded by 24-hour ambulatory blood pressure	12months