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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

Tracking Information
First Submitted Date  ICMJE December 25, 2019
First Posted Date  ICMJE January 2, 2020
Last Update Posted Date January 2, 2020
Actual Study Start Date  ICMJE December 1, 2019
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 29, 2019)
  • 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
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of SGLT2 Inhibition on OCT-A Parameters in Diabetic CKD
Official Title  ICMJE Effect of Sodium Glucose co Transporter 2 (SGLT2) Inhibition on Optical Coherence Tomography Angiography (OCT-A) Parameters in Diabetic Chronic Kidney Disease (CKD)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetic Retinopathy
  • Chronic Kidney Diseases
  • Diabetes Mellitus
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Active Comparator: Proteinuric diabetic CKD
    Tab.empagliflozin 25mg once daily for 28 days
    Interventions:
    • Drug: Empagliflozin 25 MG
    • Device: OCT-A
  • Active Comparator: Non-Proteinuric diabetic CKD
    Tab.empagliflozin 25mg once daily for 28 days
    Interventions:
    • Drug: Empagliflozin 25 MG
    • Device: OCT-A
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 29, 2019)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Wan Haslina Wan Abdul Halim, M.D +6019-6679633 afifiyad@yahoo.co.uk
Listed Location Countries  ICMJE Malaysia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04215445
Other Study ID Numbers  ICMJE FF-2019-386
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Wan Haslina Wan Abdul Halim, National University of Malaysia
Study Sponsor  ICMJE National University of Malaysia
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Wan Haslina Wan Abdul Halim, M.D Department of Ophthalmology, UKM Medical Centre
PRS Account National University of Malaysia
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP