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

NCT04215445 | Unknown Phase 4 FDA Drug FDA Device

• 1 other identifier: FF-2019-386
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetic Retinopathy; Chronic Kidney Diseases; Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Comparison of change in fovea avascular zone within retina of proteinuric and non-proteinuric chronic kidney disease patients treated with SGLT2-inhibitor

  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

  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

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

  After 28 days of treatment

Study Arms (2)

Proteinuric diabetic CKD

ACTIVE COMPARATOR

Tab.empagliflozin 25mg once daily for 28 days

Drug: Empagliflozin 25 MG; Device: OCT-A

Non-Proteinuric diabetic CKD

ACTIVE COMPARATOR

Tab.empagliflozin 25mg once daily for 28 days

Drug: Empagliflozin 25 MG; Device: OCT-A

Interventions

Empagliflozin 25 MG DRUG

Tab.empagliflozin 25mg once daily for 28 days

Also known as: Jardiance

Non-Proteinuric diabetic CKD; Proteinuric diabetic CKD

OCT-A DEVICE

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

Also known as: Cirrus HD-OCT

Non-Proteinuric diabetic CKD; Proteinuric diabetic CKD

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University of Malaysia: lead

Study Sites (1)

UKM Medical Centre

Kuala Lumpur, Kuala Lumpur, 56000, Malaysia

RECRUITING

Related Publications (27)

• Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018 Apr;138:271-281. doi: 10.1016/j.diabres.2018.02.023. Epub 2018 Feb 26.

  PMID: 29496507 BACKGROUND

• American Diabetes Association. 10. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S105-S118. doi: 10.2337/dc18-S010.

  PMID: 29222381 BACKGROUND

• National Renal Registry Malaysia. 20th report of the Malaysian Dialysis & Transplant Registry 2013. Minist Heal Malaysia. 2013. Doi: 10.1143/JJAP.35.L657

  BACKGROUND

• 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

  BACKGROUND

• Bolignano D, Zoccali C. Non-proteinuric rather than proteinuric renal diseases are the leading cause of end-stage kidney disease. Nephrol Dial Transplant. 2017 Apr 1;32(suppl_2):ii194-ii199. doi: 10.1093/ndt/gfw440.

  PMID: 28340010 BACKGROUND

• 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

  BACKGROUND

• Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM. Albuminuria and renal insufficiency prevalence guides population screening: results from the NHANES III. Kidney Int. 2002 Jun;61(6):2165-75. doi: 10.1046/j.1523-1755.2002.00356.x.

  PMID: 12028457 BACKGROUND

• Rodriguez-Poncelas A, Garre-Olmo J, Franch-Nadal J, Diez-Espino J, Mundet-Tuduri X, Barrot-De la Puente J, Coll-de Tuero G; RedGDPS Study Group. Prevalence of chronic kidney disease in patients with type 2 diabetes in Spain: PERCEDIME2 study. BMC Nephrol. 2013 Feb 22;14:46. doi: 10.1186/1471-2369-14-46.

  PMID: 23433046 BACKGROUND

• Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Cavalot F, Cignarelli M, Laviola L, Morano S, Nicolucci A, Pugliese G; Renal Insufficiency And Cardiovascular Events (RIACE) Study Group. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes. J Hypertens. 2011 Sep;29(9):1802-9. doi: 10.1097/HJH.0b013e3283495cd6.

  PMID: 21738053 BACKGROUND

• Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR; UKPDS Study Group. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes. 2006 Jun;55(6):1832-9. doi: 10.2337/db05-1620.

  PMID: 16731850 BACKGROUND

• Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015 Nov 26;373(22):2117-28. doi: 10.1056/NEJMoa1504720. Epub 2015 Sep 17.

  PMID: 26378978 BACKGROUND

• Skrtic M, Cherney DZ. Sodium-glucose cotransporter-2 inhibition and the potential for renal protection in diabetic nephropathy. Curr Opin Nephrol Hypertens. 2015 Jan;24(1):96-103. doi: 10.1097/MNH.0000000000000084.

  PMID: 25470017 BACKGROUND

• Komala MG, Panchapakesan U, Pollock C, Mather A. Sodium glucose cotransporter 2 and the diabetic kidney. Curr Opin Nephrol Hypertens. 2013 Jan;22(1):113-9. doi: 10.1097/MNH.0b013e32835a17ae.

  PMID: 23042029 BACKGROUND

• JARDIANCE current prescribing information and medication guide, www.jardiance.com. Boerhringer Ingelheim International GambH.

  BACKGROUND

• Vasilakou D, Karagiannis T, Athanasiadou E, Mainou M, Liakos A, Bekiari E, Sarigianni M, Matthews DR, Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2013 Aug 20;159(4):262-74. doi: 10.7326/0003-4819-159-4-201308200-00007.

  PMID: 24026259 BACKGROUND

• Nishimura R, Tanaka Y, Koiwai K, Inoue K, Hach T, Salsali A, Lund SS, Broedl UC. Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study. Cardiovasc Diabetol. 2015 Jan 30;14:11. doi: 10.1186/s12933-014-0169-9.

  PMID: 25633683 BACKGROUND

• Yoshizumi H, Ejima T, Nagao T, Wakisaka M. Recovery from Diabetic Macular Edema in a Diabetic Patient After Minimal Dose of a Sodium Glucose Co-Transporter 2 Inhibitor. Am J Case Rep. 2018 Apr 19;19:462-466. doi: 10.12659/ajcr.909708.

  PMID: 29670074 BACKGROUND

• Mieno H, Yoneda K, Yamazaki M, Sakai R, Sotozono C, Fukui M. The Efficacy of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors for the treatment of chronic diabetic macular oedema in vitrectomised eyes: a retrospective study. BMJ Open Ophthalmol. 2018 Jul 23;3(1):e000130. doi: 10.1136/bmjophth-2017-000130. eCollection 2018.

  PMID: 30123844 BACKGROUND

• SGLT2- inhibition with Empaglifozin Reduces Progression of Diabetic Retinopathy in Patients With High Risk of Diabetic Macular Edema (The SUPER-Trial)

  BACKGROUND

• Thompson IA, Durrani AK, Patel S. Optical coherence tomography angiography characteristics in diabetic patients without clinical diabetic retinopathy. Eye (Lond). 2019 Apr;33(4):648-652. doi: 10.1038/s41433-018-0286-x. Epub 2018 Dec 3.

  PMID: 30510234 BACKGROUND

• Goudot MM, Sikorav A, Semoun O, Miere A, Jung C, Courbebaisse B, Srour M, Freiha JG, Souied EH. Parafoveal OCT Angiography Features in Diabetic Patients without Clinical Diabetic Retinopathy: A Qualitative and Quantitative Analysis. J Ophthalmol. 2017;2017:8676091. doi: 10.1155/2017/8676091. Epub 2017 Jun 29.

  PMID: 28761762 BACKGROUND

• Sandhu HS, Eladawi N, Elmogy M, Keynton R, Helmy O, Schaal S, El-Baz A. Automated diabetic retinopathy detection using optical coherence tomography angiography: a pilot study. Br J Ophthalmol. 2018 Nov;102(11):1564-1569. doi: 10.1136/bjophthalmol-2017-311489. Epub 2018 Jan 23.

  PMID: 29363532 BACKGROUND

• Ashraf M, Nesper PL, Jampol LM, Yu F, Fawzi AA. Statistical Model of Optical Coherence Tomography Angiography Parameters That Correlate With Severity of Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2018 Aug 1;59(10):4292-4298. doi: 10.1167/iovs.18-24142.

  PMID: 30167660 BACKGROUND

• Lee DH, Yi HC, Bae SH, Cho JH, Choi SW, Kim H. Risk factors for retinal microvascular impairment in type 2 diabetic patients without diabetic retinopathy. PLoS One. 2018 Aug 9;13(8):e0202103. doi: 10.1371/journal.pone.0202103. eCollection 2018.

  PMID: 30092018 BACKGROUND

• Ting DSW, Tan GSW, Agrawal R, Yanagi Y, Sie NM, Wong CW, San Yeo IY, Lee SY, Cheung CMG, Wong TY. Optical Coherence Tomographic Angiography in Type 2 Diabetes and Diabetic Retinopathy. JAMA Ophthalmol. 2017 Apr 1;135(4):306-312. doi: 10.1001/jamaophthalmol.2016.5877.

  PMID: 28208170 BACKGROUND

• Cheung CY, Tang F, Ng DS, Wong R, Lok J, Sun Z, Tso T, Lam A, Brelen M, Chong KK, Luk AO, Chan JC, Wong TY, Tham CC. The Relationship of Quantitative Retinal Capillary Network to Kidney Function in Type 2 Diabetes. Am J Kidney Dis. 2018 Jun;71(6):916-918. doi: 10.1053/j.ajkd.2017.12.010. Epub 2018 Feb 28. No abstract available.

  PMID: 29501263 BACKGROUND

• CIRRUS HD-OCT User Manual- Models 500, 5000 ©2016 Carl Zeiss Meditec, Inc

  BACKGROUND

MeSH Terms

Conditions

Diabetic Retinopathy; Renal Insufficiency, Chronic; Diabetes Mellitus

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Wan Haslina Wan Abdul Halim, M.D

  Department of Ophthalmology, UKM Medical Centre

  STUDY CHAIR

Central Study Contacts

Wan Haslina Wan Abdul Halim, M.D

CONTACT

+6019-6679633; afifiyad@yahoo.co.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Ophthalmologist-Cornea And Anterior Segment

Study Record Dates

• First Submitted: December 25, 2019
• First Posted: January 2, 2020
• Study Start: December 1, 2019
• Primary Completion: May 1, 2020
• Study Completion: August 1, 2020
• Last Updated: January 2, 2020

Record last verified: 2019-12

Locations

MY (1)