Integrative Genetic, Molecular and Behavioural Determinants of Cognitive Decline in Type 2 Diabetes: SGLT2 Inhibitors as a Model for Secondary and Tertiary Prevention (SaveMinD)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change in Executive Cognitive Composite Score
研究概览
简要总结
This study is a prospective, randomized, open-label trial with blinded outcome assessment (PROBE design) designed to evaluate the effects of sodium-glucose cotransporter-2 (SGLT2) inhibitor therapy on cognitive function in adults with type 2 diabetes mellitus (T2D). A total of 200 participants aged 50 years or older with T2D of at least five years' duration and HbA1c ≤8.5% will be randomized in a 1:1 ratio to receive either standard diabetes care plus an SGLT2 inhibitor or standard diabetes care without an SGLT2 inhibitor. Participants will be followed for 12 months.
The primary objective is to compare changes in executive cognitive function between the two treatment groups using a composite cognitive outcome derived from standardized neuropsychological tests. Secondary objectives include assessment of global cognitive function, glycaemic variability measured by continuous glucose monitoring, metabolic control, circulating biomarkers of neurodegeneration and inflammation, functional status, and treatment safety. Baseline brain magnetic resonance imaging (MRI), APOE genotyping, frailty status, sleep quality, psychological well-being, and physical activity will be evaluated as potential modifiers of cognitive outcomes and treatment response.
The study is intended to provide prospective evidence regarding the association between SGLT2 inhibitor therapy and cognitive outcomes in adults with T2D while exploring the metabolic, neurodegenerative, and behavioural factors that may contribute to cognitive changes over time.
详细描述
Detailed Description
Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive impairment, particularly affecting executive function and processing speed. Multiple mechanisms, including chronic hyperglycaemia, glycaemic variability, vascular dysfunction, systemic inflammation, oxidative stress, and neurodegenerative processes, are thought to contribute to cognitive decline in individuals with T2D.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular and renal benefits and may also exert neuroprotective effects through improvements in metabolic control and modulation of inflammatory and vascular pathways. However, prospective randomized evidence regarding their effects on cognition remains limited.
The SaveMinD study is a prospective, randomized, open-label trial with blinded outcome assessment (PROBE design) evaluating whether the addition of an SGLT2 inhibitor to standard diabetes care influences cognitive outcomes in adults with T2D over 12 months. The primary endpoint is change in executive cognitive function, assessed using a composite score derived from standardized neuropsychological tests. Secondary outcomes include global cognitive function, glycaemic control and variability, circulating biomarkers of neurodegeneration and inflammation, physical activity, functional status, sleep quality, psychological well-being, and safety.
The study also incorporates baseline structural brain magnetic resonance imaging (MRI), APOE genotyping, frailty assessment, continuous glucose monitoring, and objective physical activity monitoring to explore biological and behavioural factors associated with cognitive change. These assessments will be used to investigate potential mechanisms underlying cognitive decline and to identify factors that may modify the response to SGLT2 inhibitor therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The study follows a Prospective Randomized Open-label Blinded Endpoint (PROBE) design. Owing to the nature of the intervention, participants and treating physicians will not be blinded to treatment allocation. However, investigators performing cognitive assessments, data management, and statistical analyses will remain blinded throughout the study. Laboratory personnel responsible for biomarker analyses will also be blinded to treatment allocation.
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adults aged 50 years or older.
- •diagnosis of type 2 diabetes mellitus according to current American Diabetes - - association (ADA) diagnostic criteria.
- •duration of type 2 diabetes mellitus of at least 5 years.
- •glycated haemoglobin (HbA1c) ≤8.5% (≤69 mmol/mol) at screening.
- •estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m².
- •stable glucose-lowering therapy for at least 3 months before enrolment.
- •able to complete neuropsychological assessments and all study procedures.
- •willing and able to wear a continuous glucose monitoring (CGM) sensor and a physical activity monitor.
- •able to provide written informed consent.
排除标准
- •previous or current treatment with a sodium-glucose cotransporter-2 (SGLT2) inhibitor.
- •Montreal Cognitive Assessment (MoCA) score <20 at screening.
- •diagnosis of dementia or another major neurocognitive disorder.
- •history of stroke or transient ischaemic attack within the previous 6 months.
- •Parkinson's disease, multiple sclerosis, epilepsy, or another major neurological disorder affecting cognitive function.
- •severe psychiatric illness likely to interfere with study participation or cognitive assessment.
- •estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m².
- •history of diabetic ketoacidosis.
- •recurrent urinary tract infections (≥3 episodes during the previous year).
- •contraindication to magnetic resonance imaging (MRI).
- •pregnancy, breastfeeding, or planned pregnancy during the study period.
- •active malignancy requiring systemic treatment (except adequately treated non-melanoma skin cancer).
- •moderate or severe hepatic impairment (Child-Pugh Class B or C).
- •alcohol or substance abuse likely to interfere with study participation.
- •presence of an established indication for mandatory SGLT2 inhibitor therapy according to current international clinical practice guidelines (e.g., symptomatic heart failure or chronic kidney disease).
- •participation in another interventional clinical trial within the previous 30 days.
- •any medical condition that, in the opinion of the investigator, could compromise participant safety, adherence to the protocol, or interpretation of study results.
结局指标
主要结局
Change in Executive Cognitive Composite Score
时间窗: Baseline to 12 months
The primary outcome is the between-group difference in change from baseline to Month 12 in the Executive Cognitive Composite Score. The Executive Cognitive Composite Score is a standardized composite measure of executive function and processing speed calculated by averaging z-scores from the Digit Symbol Substitution Test, Trail Making Test Part A and Part B (using the Part B minus Part A completion time), the Digit Span Backward Test, and Verbal Fluency Tests (letter fluency and semantic/category fluency). The composite score is expressed as a standardized z-score and therefore has no fixed theoretical minimum or maximum value. Higher scores indicate better executive cognitive performance.
次要结局
- Change in Montreal Cognitive Assessment (MoCA) Score(Baseline to 12 months)
- Change in Glycaemic Variability Assessed by Continuous Glucose Monitoring(Baseline, 6 months, and 12 months)
- Change in HbA1c(Baseline, 6 months, and 12 months)
- Change in High-Sensitivity C-Reactive Protein (hsCRP)(Baseline to 12 months)
- Change in Neurofilament Light Chain (NfL)(Baseline to 12 months)
- Change in Moderate-to-Vigorous Physical Activity(Baseline, 6 months, and 12 months)
- Incidence of Adverse Events and Serious Adverse Events(From baseline to 12 months)
- Change in Sleep Quality(Baseline, 6 months, and 12 months)
- Change in Anxiety and Depression Symptoms(Baseline, 6 months, and 12 months)
- Change in Perceived Stress(Baseline, 6 months, and 12 months)
- Change in Interleukin-6 (IL-6)(Baseline and Month 12)
- Change in Tumour Necrosis Factor-Alpha (TNF-α)(Baseline and Month 12)
- Change from Baseline to Month 12 in Time in Range (3.9-10.0 mmol/L)(Baseline, 6 months, 12 months.)
- Change from Baseline to Month 12 in Time Below Range (<3.9 mmol/L)(Baseline, 6 months, 12 months)
- Change in Glial Fibrillary Acidic Protein (GFAP)(Baseline to 12 month)
- Change in Phosphorylated Tau217 (p-tau217)(Baseline and Month 12)
- Change in Amyloid-beta42 (Aβ42)(Baseline and month 12)
研究者
JanaKomel
MD, Internal Medicine Specialist
University of Primorska