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

December 29, 2019 updated by: Wan Haslina Wan Abdul Halim, National University of Malaysia

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

90

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Malaysia
    • Wilayah Persekutuan
      • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 56000
        • Recruiting
        • UKM Medical Centre
        • Contact:
        • Principal Investigator:
          • Wan Haslina Wan Abdul Halim, M.D
        • Sub-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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Proteinuric diabetic CKD
Tab.empagliflozin 25mg once daily for 28 days
Drug: Empagliflozin 25 MG
Tab.empagliflozin 25mg once daily for 28 days
Other Names:
  • Jardiance
Device: OCT-A
Optical coherence tomography angiography (OCT-A) is a non-invasive method to study the microvasculature of the retina and choroid.
Other Names:
  • Cirrus HD-OCT
Active Comparator: Non-Proteinuric diabetic CKD
Tab.empagliflozin 25mg once daily for 28 days
Drug: Empagliflozin 25 MG
Tab.empagliflozin 25mg once daily for 28 days
Other Names:
  • Jardiance
Device: OCT-A
Optical coherence tomography angiography (OCT-A) is a non-invasive method to study the microvasculature of the retina and choroid.
Other Names:
  • Cirrus HD-OCT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of change in fovea avascular zone within retina of proteinuric and non-proteinuric chronic kidney disease patients treated with SGLT2-inhibitor
Time Frame: After 28 days of treatment
Change in fovea vascular zone (FAZ) size (um2) from Baseline using Optical Coherence Tomography Angiography (OCT-A) post-SGLT-2 treatment
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
Time Frame: After 28 days of treatment
Change in vessel density (mm-1) from Baseline using Optical Coherence Tomography Angiography (OCT-A) post-SGLT-2 treatment
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
Time Frame: After 28 days of treatment
Change in perfusion density from Baseline using Optical Coherence Tomography Angiography (OCT-A) post-SGLT-2 treatment
After 28 days of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National University of Malaysia

Investigators

  • Study Chair: Wan Haslina Wan Abdul Halim, M.D, Department of Ophthalmology, UKM Medical Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2019

Primary Completion (Anticipated)

May 1, 2020

Study Completion (Anticipated)

August 1, 2020

Study Registration Dates

First Submitted

December 25, 2019

First Submitted That Met QC Criteria

December 29, 2019

First Posted (Actual)

January 2, 2020

Study Record Updates

Last Update Posted (Actual)

January 2, 2020

Last Update Submitted That Met QC Criteria

December 29, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FF-2019-386

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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