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

Sponsor
National University of Malaysia (Other)
Overall Status
Unknown status
CT.gov ID
NCT04215445
Collaborator
(none)
90
1
2
8
11.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Empagliflozin 25 MG
  • Device: OCT-A
Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Effect of Sodium Glucose co Transporter 2 (SGLT2) Inhibition on Optical Coherence Tomography Angiography (OCT-A) Parameters in Diabetic Chronic Kidney Disease (CKD)
Actual Study Start Date :
Dec 1, 2019
Anticipated Primary Completion Date :
May 1, 2020
Anticipated Study Completion Date :
Aug 1, 2020

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. 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]

      Change in fovea vascular zone (FAZ) size (um2) from Baseline using Optical Coherence Tomography Angiography (OCT-A) post-SGLT-2 treatment

    2. 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]

      Change in vessel density (mm-1) from Baseline using Optical Coherence Tomography Angiography (OCT-A) post-SGLT-2 treatment

    3. 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]

      Change in perfusion density from Baseline using Optical Coherence Tomography Angiography (OCT-A) post-SGLT-2 treatment

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    35 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UKM Medical Centre Kuala Lumpur Wilayah Persekutuan Malaysia 56000

    Sponsors and Collaborators

    • National University of Malaysia

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Wan Haslina Wan Abdul Halim, Consultant Ophthalmologist-Cornea And Anterior Segment, National University of Malaysia
    ClinicalTrials.gov Identifier:
    NCT04215445
    Other Study ID Numbers:
    • FF-2019-386
    First Posted:
    Jan 2, 2020
    Last Update Posted:
    Jan 2, 2020
    Last Verified:
    Dec 1, 2019
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jan 2, 2020