Effect of SGLT2 Inhibition on Aging-related Biomarkers in Older Obese Adults With Pre-diabetes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- AGE-RAGE Measurement in Plasma
研究概览
简要总结
Inhibitors of the sodium-glucose co-transporter (SGLT2) are FDA-approved for the treatment of type 2 diabetes (T2DM). Their mechanism of action involves lowering of blood glucose concentration secondary to increased glucose excretion of glucose by the kidney. These drugs also improve body weight, blood pressure, and cardiac function. Based on these pleiotropic effects, including its calorie restriction-mimetic properties, the study team hypothesize that SGLT2 drugs will impact several basic aging-related processes, including reductions in oxidative damage to DNA and proteins, advanced glycation end products (AGE) and receptor for AGE (RAGE), cellular senescence, and mitochondrial function.
详细描述
Investigations into the aging process have identified major cellular dysfunctions that contribute to aging, including but not limited to increased burden of damaged DNA and protein, reduction in mitochondrial respiration, and the development of pro-inflammatory senescent cells. Developing and testing interventions that interact with multiple points of this spectrum may delay the aging process. Based on prior investigations, the study team believe the SGLT2 inhibitor class of drugs may target these basic mechanisms involved in the aging process and propose testing in a high-risk human population to evaluate their effectiveness in ameliorating aging-associated dysfunctions. Specifically, the investigators hypothesize that SGLT2i drugs will lead to reductions in oxidative damage to DNA and proteins, AGE-RAGE, and cellular senescence, which will be accompanied by improvements in mitochondrial function. If the hypothesis is correct, these findings could lead to the development of new approaches to increase both health-span and lifespan.
This is a single center, open-label, randomized controlled trial. The target enrollment for this pilot study is 20 completed subjects, split evenly between experimental and control groups. Each subject will be randomized to either the experimental group of dapagliflozin 10mg daily for 12 weeks or the control group of nutritional counseling for weight loss. Health-span and clinical evaluations will be taken at baseline and at weeks 10-12 of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men or post-menopausal women.
- •Age= 60+ years.
- •All ethnic groups.
- •Body Mass index (BMI) between 30-38 kg/m
- •Diagnosis of pre-diabetes (HbA1c 5.7-6.4% and 2 hr. Oral Glucose Tolerance Test (OGTT) glucose between 140-199 mg/dL, evaluated at Visit 1 and 2).
- •Stable body weight (±3% for ≥3 months).
- •Willing to adhere to medication regimen for three months.
- •Montreal Cognitive Assessment score ≥21
排除标准
- •Diagnosis of diabetes based on American Diabetes Association (ADA) criteria
- •Impaired renal function with estimated Glomerular Filtration Rate (eGFR) < 45 mL/min/1.73m2 .
- •Impaired liver function with labs ≥3 times upper limits of normal range
- •Abnormal hematocrit with lower limits of ≤30%
- •Abnormal triglycerides with upper limits ≥600 mg/dL
- •Abnormal Thyroid stimulating hormone (TSH) values ≤0.3 and ≥10
- •Urinalysis results with ˃ 5-10 white blood cell count
- •Concomitant medications known to affect glucose and lipid homeostasis (anti-diabetes medications, glucocorticoids, atypical antipsychotics, anti-transplant rejection medications, anti-retrovirals).
- •Current treatment with anticoagulants (warfarin). Aspirin (up to 325 mg) and clopidogrel will be permitted if these can be held for seven days prior to the biopsies.
- •History of recent cardiovascular event in the last 6 months or Heart Failure (New York Heart Classification greater than class III-IV; recent EKG changes that suggest active heart disease
- •Poorly controlled blood pressure (systolic BP>180, diastolic BP>100 mmHg).
- •Active inflammatory, autoimmune, infectious, hepatic, gastrointestinal, malignant, and uncontrolled psychiatric disease (Subjects with depression, anxiety, PTSD, etc. can enroll if controlled and on stable medication)
- •Blood donation within 2 months prior to enrollment
- •History of frequent UTI
研究组 & 干预措施
Dapagliflozin
10 participants with pre-diabetes will be randomized to the experimental group to receive dapagliflozin 10mg by mouth daily for 12 weeks.
干预措施: Dapagliflozin 10 mg (Drug)
Nutritional Counseling
10 participants with pre-diabetes will be randomized to receive nutritional counseling weekly for 12 weeks
干预措施: Nutritional counseling (Behavioral)
结局指标
主要结局
AGE-RAGE Measurement in Plasma
时间窗: Baseline to 12 weeks
Change in AGE-RAGE measured by enzyme-linked immunosorbent assay (ELISA).
次要结局
- Grip Strength(Baseline to 12 weeks)
- 6 Minute Walking Distance(Baseline to 12 weeks)