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

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ClinicalTrials.gov Identifier: NCT04215445
Recruitment Status : Recruiting
First Posted : January 2, 2020
Last Update Posted : January 2, 2020
Sponsor:
Information provided by (Responsible Party):
Wan Haslina Wan Abdul Halim, National University of Malaysia

Study Description
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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Diabetic Retinopathy Chronic Kidney Diseases Diabetes Mellitus 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
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Study Type : Interventional  (Clinical Trial)
Estimated 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 : December 1, 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arms and Interventions
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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 Name: 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 Name: 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 Name: 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 Name: Cirrus HD-OCT


Outcome Measures
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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 [ 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

  2. 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

  3. 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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04215445


Contacts
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Contact: Wan Haslina Wan Abdul Halim, M.D +6019-6679633 afifiyad@yahoo.co.uk

Locations
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Malaysia
UKM Medical Centre Recruiting
Kuala Lumpur, Wilayah Persekutuan, Malaysia, 56000
Contact: Wan Haslina Wan Abdul Halim, M.D    +6019-6679633    afifiyad@yahoo.co.uk   
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         
Sponsors and Collaborators
National University of Malaysia
Investigators
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Study Chair: Wan Haslina Wan Abdul Halim, M.D Department of Ophthalmology, UKM Medical Centre
More Information
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Publications:
National Renal Registry Malaysia. 20th report of the Malaysian Dialysis & Transplant Registry 2013. Minist Heal Malaysia. 2013. Doi: 10.1143/JJAP.35.L657
Port J Nephrol Hypert 2017; 31(2): 122-131 • Advance Access publication 29 May 2017. Diabetic Nephropathy and its two phenotypes: the proteinuric and non-proteinuric Regina Silva, Catarina Meng, Luís Coentrão
Perez-Monteoliva, N. R., Robles et al. Non-proteinuric diabetic nephropathy is the main cause of chronic kidney disease. Journal of Hypertension: June 2018 - Volume 36 - Issue - p e11. doi: 10.1097/01.hjh.0000538992.55964.f1
JARDIANCE current prescribing information and medication guide, www.jardiance.com. Boerhringer Ingelheim International GambH.
SGLT2- inhibition with Empaglifozin Reduces Progression of Diabetic Retinopathy in Patients With High Risk of Diabetic Macular Edema (The SUPER-Trial)
CIRRUS HD-OCT User Manual- Models 500, 5000 ©2016 Carl Zeiss Meditec, Inc

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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: January 2, 2020    Key Record Dates
Last Update Posted: January 2, 2020
Last Verified: December 2019

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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:
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Diabetic Retinopathy
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Renal Insufficiency
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
 Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs