Effects of SGLT2i on the Cognitive Function in T2DM Patient (ESCDP) (ESCDP)

Effects of Sodium-glucose Co-transporter-2 Inhibitors on the Cognitive Function in Type 2 Diabetic Patient

Type 2 diabetes is associated with diabetic cognopathy, the prevalence of Alzheimer's Disease(AD) in T2DM patients is 1.5 to 2.5 times higher than the general population. Cognitive impairment seriously affects the health and quality of life of the elderly. Prevention and treatment measures for cognitive decline in persons with T2DM has not been well studied.

Sodium-glucose transporter-2 (SGLT-2) inhibitors, which lower serum glucose by inhibiting SGLT2-mediated glucose reabsorption in renal proximal tubules, could be neuroprotective. It was recently reported that the SGLT-2 inhibitor improved cognitive function and ameliorated oxidative stress via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in mice or HFD-induced obese rats, that means SGLT-2 inhibitor may provide neuroprotection in the diabetic brain. Hence, Invokana (Canagliflozin) might act as a potent dual inhibitor of AChE and SGLT2. Since the development of diabetes is associated with AD, the design of new AChE inhibitors based on antidiabetic drug scaffolds would be particularly beneficial. Moreover, the present computational study reveals that Invokana (Canagliflozin) is expected to form the basis of a future dual therapy against diabetes associated neurological disorders.

The overall goal of this study is to explore the effects of SGLT2 inhibitor on the cognitive function in patients with type 2 diabetes mellitus and make further contribution to the improvement of cognitive function.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Cognitive Functions Confusion
• Intervention / Treatment: Drug: Canagliflozin; Drug: Sitagliptin

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Zhiming Zhu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly onset type 2 diabetes within 3 months
• 7%<HbA1c<10%

Exclusion Criteria:

• Type 2 diabetes with acute diabetic complications.
• Type1 diabetes.
• Thyroid dysfuncition.
• Any surgical or medical conditions that significantly influence absorption, distribution, metabolism or excretion of the intervention drugs.
• History of cardio-cerebral vascular events, such as congestive heart failure, myocardial infarction or stroke within 3 months.
• Hepatic insufficiency (AST or AST is twice higher than the upper limit) or history of hepatitis or cirrhosis, hepatic encephalopathy.
• Renal insufficiency (serum creatinine 1.5 times higher than the upper limit) or history of dialysis and nephritic syndrome.
• Acute infections, tumor, severe arrhythmia.
• Alcohol or medicine addiction, psychoactive substance abuse.
• Other diseases affecting cognitive function (congenital dementia, brain trauma, parkinson's diseases, toxicencephacopathy,epilepsy, mental disorders, severe lungdy sfunction, epilepsy, severe hypoglycemic coma, cerebrovascular disease, ischemic heart disease, etc.)
• Fertile woman without contraceptives.
• Allergic to or have contraindication to the intervention drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canagliflozin; 12 weeks of Canagliflozin(100mg/day) treatment, randomly	Drug: Canagliflozin; 12 weeks of Canagliflozin(100mg/day) treatment
Experimental: Sitagliptin; 12 weeks of Sitagliptin (100mg/day) treatment, randomly	Drug: Sitagliptin; 12 weeks of Sitagliptin (100mg/day) treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of cognitive function assessed by cognitive function scale	cognitive function scale	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of standardized uptake values of brain and splanchnic organs assessed by 18F-PET-CT	18F-PET-CT	1 week
Changes of brain function assessed by near infrared brain functional imaging	near infrared brain functional imaging	4 week
Changes of urinary sodium and glucose excretion (mmol/24h)	urinary sodium and glucose excretion	1 week

Collaborators and Investigators

• Sponsor: Third Military Medical University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): December 1, 2023
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: March 9, 2020
• First Submitted That Met QC Criteria: March 9, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes mellitus; Cognitive Functions; Sodium glucose transporter
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Confusion; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Canagliflozin
• Other Study ID Numbers: ESCDP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No