Clinical trial NCT05310916: Effect of SGLT2i on Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients
Official title: Evaluation of the Effect of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors on Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Diabetic Retinopathy
Keywords: Diabetic retinopathy
Sodium-glucose cotransporter-2 inhibitor
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2022-04-05
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: A prospective, randomized, open-label, controlled clinical trial will be conducted at the endocrinology department - Ain Shams University (ASU) hospital. Sixty patients will be enrolled into the study. 30 of which will receive dapagliflozin 10mg tab once daily and the other thirty will receive their standard antidiabetic therapy for 12 weeks.

Detailed description: All type 2 diabetes mellitus patients presenting to the endocrinology department, ASU Hospitals, who were diagnosed with mild to moderate non-proliferative diabetic retinopathy will be assessed for eligibility.

Eligible patients will be randomly assigned to one of the following 2 arms:

1. Group 1 (Control group) (n= 30): type 2 diabetes mellitus patients who will receive their oral antidiabetic for 12 weeks.
2. Group 2 (Test group) (n= 30): type 2 diabetes mellitus patients who will receive their oral antidiabetic along with dapagliflozin at a dose of 10 mg daily for 12 weeks.

A total of four visits one for baseline evaluation and one for end of study evaluation and two intermediate visits, the following will be performed in the visits:

1. Clinical Evaluation

   1. Systolic and diastolic blood pressures recording.
   2. Plasma glucose measurement.
2. Report any adverse effects that may appear
3. Blood samples will be taken at baseline and at 12-week visits
4. Follow up

Eligibility criteria: Inclusion Criteria:

1. Female or male aged between 40 and 70 years old.
2. Glomerular filtration rates \> 60 mL/min.
3. Normal aspartate and alanine transaminase levels.
4. Controlled systolic and diastolic blood pressures

Exclusion Criteria:

1. Patients using insulin or more than one oral anti-diabetic drug.
2. Patients who have HbA1c level ≥10% (86 mmol/mol) or a fasting plasma glucose level \>240 mg/dl.
3. Patients with a history of cardiovascular events within six months before enrolment.
4. Patients suffering from cataract or glaucoma.
5. Patients with volume depletion clinical signs.
6. Body mass index (BMI) \>40 kg/m2
7. Infectious or inflammatory diseases.
8. Neoplasm, or hematological disorders.
9. Pregnant or breast-feeding patients.
10. Active participation in another clinical study.

Primary outcomes:
measure: Severity of retinopathy
timeFrame: 12 weeks
measure: Evaluation of the study biomarkers, IL-6, and VEGF
timeFrame: 12 weeks
Secondary outcomes:
measure: Occurrence of adverse events
timeFrame: (1-90)days
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Internal medicine and endocrinology department, Ain-shams university hospitals
Study officials:
affiliation: Faculty of pharmacy Ain Shams University
name: Lamiaa M ElWakeel, PhD
role: STUDY_DIRECTOR
affiliation: Faculty of Medicine Ain Shams University
name: Mona A Abd El Salam, MD
role: STUDY_DIRECTOR
affiliation: Faculty of pharmacy Ain Shams University
name: Marwa A Ahmed, PhD
role: STUDY_DIRECTOR
affiliation: Faculty of pharmacy Ain Shams University
name: Nidae A Ismail, BSc
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Wong TY, Cheung CM, Larsen M, Sharma S, Simo R. Diabetic retinopathy. Nat Rev Dis Primers. 2016 Mar 17;2:16012. doi: 10.1038/nrdp.2016.12.
citation: Sha W, Wen S, Chen L, Xu B, Lei T, Zhou L. The Role of SGLT2 Inhibitor on the Treatment of Diabetic Retinopathy. J Diabetes Res. 2020 Nov 12;2020:8867875. doi: 10.1155/2020/8867875. eCollection 2020.
citation: Zhou Z, Ju H, Sun M, Chen H. Serum Vascular Endothelial Growth Factor Levels Correlate with Severity of Retinopathy in Diabetic Patients: A Systematic Review and Meta-Analysis. Dis Markers. 2019 Mar 24;2019:9401628. doi: 10.1155/2019/9401628. eCollection 2019.
citation: Yao Y, Li R, Du J, Long L, Li X, Luo N. Interleukin-6 and Diabetic Retinopathy: A Systematic Review and Meta-Analysis. Curr Eye Res. 2019 May;44(5):564-574. doi: 10.1080/02713683.2019.1570274. Epub 2019 Feb 4.
citation: Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015 Sep;38(9):1687-93. doi: 10.2337/dc15-0843. Epub 2015 Jun 15.
citation: Lahoti S, Nashawi M, Sheikh O, Massop D, Mir M, Chilton R. Sodium-glucose co-transporter 2 inhibitors and diabetic retinopathy: insights into preservation of sight and looking beyond. Cardiovasc Endocrinol Metab. 2020 May 18;10(1):3-13. doi: 10.1097/XCE.0000000000000209. eCollection 2021 Mar.
citation: Chen YY, Wu TT, Ho CY, Yeh TC, Sun GC, Kung YH, Wong TY, Tseng CJ, Cheng PW. Dapagliflozin Prevents NOX- and SGLT2-Dependent Oxidative Stress in Lens Cells Exposed to Fructose-Induced Diabetes Mellitus. Int J Mol Sci. 2019 Sep 5;20(18):4357. doi: 10.3390/ijms20184357.
citation: Ott C, Jumar A, Striepe K, Friedrich S, Karg MV, Bramlage P, Schmieder RE. A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation. Cardiovasc Diabetol. 2017 Feb 23;16(1):26. doi: 10.1186/s12933-017-0510-1.