Effect of SGLT2 Inhibition on OCT-A Parameters in Diabetic CKD

Effect of Sodium Glucose co Transporter 2 (SGLT2) Inhibition on Optical Coherence Tomography Angiography (OCT-A) Parameters in Diabetic Chronic Kidney Disease (CKD)

Sponsors

Lead Sponsor: National University of Malaysia

Source National University of Malaysia
Brief Summary

Diabetes mellitus is a major and growing problem worldwide with many known micro and macrovascular complications. According to International Diabetes Federation, there were 285 million adults diagnosed with diabetes in 2010 and expected to increase to 439 million adult in 2030. It is a leading cause of chronic kidney disease (CKD) followed by hypertension, glomerulonephritis, and cystic kidney disease. Renal impairment patients metabolize and excrete drugs differently from patients with normal renal function and hence only limited number of oral hypoglycemic agent (OHA) available for them. One of the choices is sodium glucose co-transporter-2 inhibitor (SGLT2i) which is now widely used. Apart from its nephroprotective advantage, it also has additional benefit on cardiovascular and renal function based on EMPA-REG OUTCOME trial. One of the examples of SGLT2i is Empagliflozin (JARDIANCE) tablet, which has FDA U.S. Approval in 2014. It acts by reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thus increases urinary glucose excretion. It can cause osmotic diuresis, which may lead to intravascular volume contraction. Apart from its additional cardiovascular and nephroprotective effect, SGLT2 inhibitor might have additional protective effect to the eye. Nowadays, optical coherence tomography angiography (OCT-A) has emerged as one of a non-invasive methods to study the microvasculature of the retina and choroid. Many studies had discussed regarding-pre clinical changes present on OCT-A in patients without clinical diabetic retinopathy. These pre-clinical changes includes capillary dropout, microaneurysm, neovascularization, venous beading and enlargement of fovea avascular zone. However, there are minimal data and publications on different type of diabetic CKD with OCT-A parameters in diabetic patients. The purpose of this study is to determine the effect of short term SGLT2 inhibition on OCT-A parameters (fovea avascular zone (FAZ) size, vessel density and perfusion density) in diabetic CKD.

Detailed Description

This is a prospective, single-centred, open-labeled, randomized clinical trial conducted in ,University Kebangsaan Malaysia Medical Centre (UKMMC). This is also a Quasi-experimental study and all patients from Endocrine, Nephrology and Ophthalmology Clinic in UKM Medical Centre from November 2019 till November 2021 will be involved in this study. Patients who fulfill the inclusion criteria will be included in this study. All eligible subjects will be asked to sign an informed consent.

Participants will be randomized into two groups, diabetic patient with proteinuria and diabetic patient without proteinuria. Participants will be interviewed on demographic data (age, gender, race, blood pressure, Body Mass Index) will be taken. Urine sample and peripheral blood (2-3ml) is collected from patients in sterile container (EDTA tube) and will be sent for urine albumin creatinine ratio (ACR) and HbA1c test. The eye with best fundal and signal view on OCT-A will be chosen or if both eyes similar, right eye will be chosen. Pre-treatment tests fundus photo and OCT-A measurement will be taken at eye clinic after dilating the pupils with 1% tropicamide and 2.5% phenylephrine hydrochloride. Fundus examination is taken using a digital mydriatic retinal camera (Topcon Retinal Camera TRC-50DX (type 1A), Tokyo Japan. OCT-A measurement is taken by using Cirrus HD-OCT, 2016 Carl Zeiss Meditec.

Then Tab.empagliflozin 25mg once daily for 28 days will be given to both group of patients proteinuric and non proteinuric diabetic CKD. After 28 days, post-treatment tests of fundus examination and OCT-A measurement will be taken at eye clinic.

The statistical data analysis will be performed using statistical package for Social Science, version 22.0 (SPSS, Inc. Chicago III USA) for IOS. The OCT-A parameters studied (FAZ size, vessel density and perfusion density) will be used as main response variables. All variables will be defined by method of descriptive statistics. The analysis of quantitative variables includes a calculation of mean and standard deviation. T test will be performed to test the significant between the 2 groups. Correlation will be measured with Pearson correlation coefficient. A p <0.05 will be considered as statistically significant.

Overall Status Recruiting
Start Date December 1, 2019
Completion Date August 2020
Primary Completion Date May 2020
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Comparison of change in fovea avascular zone within retina of proteinuric and non-proteinuric chronic kidney disease patients treated with SGLT2-inhibitor After 28 days of treatment
Comparison of change in retinal and choroidal vessel density in proteinuric and non-proteinuric chronic kidney disease patients treated with SGLT2-inhibitor After 28 days of treatment
Comparison of change in retinal and choroidal vascular perfusion density in proteinuric and non-proteinuric chronic kidney disease patients treated with SGLT2-inhibitor After 28 days of treatment
Enrollment 90
Condition
Intervention

Intervention Type: Drug

Intervention Name: Empagliflozin 25 MG

Description: Tab.empagliflozin 25mg once daily for 28 days

Other Name: Jardiance

Intervention Type: Device

Intervention Name: OCT-A

Description: Optical coherence tomography angiography (OCT-A) is a non-invasive method to study the microvasculature of the retina and choroid.

Other Name: Cirrus HD-OCT

Eligibility

Criteria:

Inclusion Criteria:

- Patients diagnosed with Type 2 DM with CKD (eGFR 45 - 60 ml/min/1.7m2)

- Age between 35 and 65 year old

- Patients able to give informed consent to participate in the study.

- Patients previously not on tablet Empagliflozin

Exclusion Criteria:

- Heart or respiratory failure, recent MI, shock, hypotension

- Pregnancy or lactation.

- Known case of CKD due to other causes such as hypertension, renal calculi, analgesic nephropathy

- Patients with multiple diuretic use.

- Hypersensitivity reactions to SGLT2 group of agents

- Patient underwent previous ocular intervention (surgery, laser or intraocular injection) within 3 months

- Dense cataract which could obscured the fundal view and signal strength on OCT-A

- HbA1c more than 10%

- Systolic blood pressure more than 180mmHg

Gender: All

Minimum Age: 35 Years

Maximum Age: 65 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Wan Haslina Wan Abdul Halim, M.D Study Chair Department of Ophthalmology, UKM Medical Centre
Overall Contact

Last Name: Wan Haslina Wan Abdul Halim, M.D

Phone: +6019-6679633

Email: [email protected]

Location
Facility: Status: Contact: Investigator: UKM Medical Centre Wan Haslina Wan Abdul Halim, M.D +6019-6679633 [email protected] Wan Haslina Wan Abdul Halim, M.D Principal Investigator Yong Meng Hsien, M.D Sub-Investigator Norasyikin A. Wahab, M.D Sub-Investigator Rozita Mohd, M.D Sub-Investigator Ruslinda Mustafar, M.D Sub-Investigator Siti Husna Hussein, M.D Sub-Investigator
Location Countries

Malaysia

Verification Date

December 2019

Responsible Party

Type: Principal Investigator

Investigator Affiliation: National University of Malaysia

Investigator Full Name: Wan Haslina Wan Abdul Halim

Investigator Title: Consultant Ophthalmologist-Cornea And Anterior Segment

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Proteinuric diabetic CKD

Type: Active Comparator

Description: Tab.empagliflozin 25mg once daily for 28 days

Label: Non-Proteinuric diabetic CKD

Type: Active Comparator

Description: Tab.empagliflozin 25mg once daily for 28 days

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov