Individual Albuminuria Lowering Response to Dapagliflozin in a Decentralized Clinical Trial in Patients With Type 2 Diabetes Mellitus and Elevated Albuminuria
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- UACR response
研究概览
简要总结
Randomized placebo-controlled double-blind cross-over N=1 trial in adult male and female patients with UACR >20 mg/g (2.26 mg/mmol) with type 2 diabetes treated in primary or secondary healthcare.
The goal of this clinical trial is to determine the individual response to the SGLT2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR). Secondary objectives are to determine the individual response to dapagliflozin in systolic blood pressure, body weight, eGFR, and fasting plasma glucose.
Participants will collect all study data in the comfort of their own environments:
- First-morning void urine samples
- Capillary blood samples
- Blood pressure
- Body weight
Participants will be randomly assigned to a cross-over study consisting of two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with a 1-week wash-out period between every treatment period to avoid cross-over effects.
详细描述
Rationale:
Persistent increased albuminuria is a strong risk marker for progressive kidney disease and cardiovascular disease in patients with or without diabetes. The degree of albuminuria reduction in the first months of treatment with pharmacological or dietary intervention correlates with the degree of long-term (3 to 4 years) renal or cardiovascular protection. Despite the various available treatments to decrease urinary albumin excretion, residual albuminuria persists in many patients. The high residual albuminuria in a proportion of patients is at least in part explained by suboptimal response to the current treatments (i.e., ACE inhibitor or Angiotensin Receptor Blockers).
Dapagliflozin is a sodium-glucose transport inhibitor and inhibits the reabsorption of glucose in the proximal tubule. This leads to a decrease in fasting plasma glucose and HbA1c in patients with type 2 diabetes. In addition, dapagliflozin administration causes a decrease in blood pressure and body weight and an increase in hematocrit suggestive of a diuretic effect. Previous studies have also demonstrated the albuminuria lowering effects of dapagliflozin in patients with type 2 diabetes mellitus.
Although dapagliflozin markedly slows progression of kidney function decline (and reduces cardiovascular outcomes) on a population level, randomized parallel group trials have suggested a marked variation in the response to dapagliflozin between individual patients. By design, randomized parallel group placebo-controlled clinical trials test the efficacy of new interventions on a population level but do not assess the efficacy of a drug for the individual. Although there is variation in response between patients, parallel group trial does not allow conclusions whether this variation is a true variation in drug response, or measurement or temporal random variation. The investigators therefore propose a cross-over trial with repeated administration (i.e., a series of N=1 trials) to ascertain the individual drug response. This design specifically allows for assessment of drug efficacy and safety at an individual level.
Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Diagnosis of type 2 diabetes mellitus
- •Urinary albumin-to-creatinine ratio >20 mg/g (2.26 mg/mmol)
- •eGFR >30 ml/min/1.73m2
- •Willing to sign informed consent
排除标准
- •Diagnosis of type 1 diabetes
- •Prior treatment with SGLT2 inhibitor in the four weeks prior to randomization
- •History of severe hypersensitivity or contraindications to dapagliflozin
- •Unable to monitor blood pressure / body weight or handle digital technologies
- •History of non-adherence to medical regimens or unwillingness to comply with the study protocol
- •Participation in any clinical investigation within 3 months prior to initial dosing
- •Unstable or rapidly progressing renal disease
- •Severe hepatic impairment (Child-Pugh class C) as determined by the treating physician.
- •Active malignancy
- •Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: History of active inflammatory bowel disease, within the last six months; Major gastrointestinal tract surgery as decided by the treating physician; Pancreatitis within the last six months; Evidence of serious hepatic disease as determined by the treating physician; Evidence of urinary obstruction or difficulty in voiding at screening.
- •Confirmed lactose intolerance demonstrated with a lactose intolerance test.
- •Donation or loss of 400 mL of blood within 8 weeks prior to initial dosing
- •History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening
- •Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
- •Current pregnancy or breast feeding / attempting to conceive.
- •Women of childbearing potential (WOCBP): WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner the risk of pregnancy is minimized; WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent of HCG) within 0 to 72 hours before the first dose of study drug.
- •WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below). The following women are WOCBP:
- •Women using the following methods to prevent pregnancy: oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides).
- •Women who are practicing abstinence.
- •Women who have a partner who is sterile (e.g. due to vasectomy).
- •Post-menopause is defined as:
- •Women who have had amenorrhea for >12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH) level >35 mIU/mL.
- •Women who have irregular menstrual periods and a documented serum FSH level >35 mIU/mL.
- •Women who are taking hormone replacement therapy (HRT).
研究组 & 干预措施
Option 1 (D-D-P-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Dapagliflozin 10mg Tab (Drug)
Option 1 (D-D-P-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Placebo (Drug)
Option 1 (D-D-P-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Withings BPM Connect (Device)
Option 1 (D-D-P-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Withings Body+ (Device)
Option 1 (D-D-P-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Hem-Col Capillary Blood Collection Device (Diagnostic Test)
Option 1 (D-D-P-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: MEMS (Medication Electronic Monitoring System) Cap (Device)
Option 2 (D-P-D-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Dapagliflozin 10mg Tab (Drug)
Option 2 (D-P-D-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Placebo (Drug)
Option 2 (D-P-D-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Withings BPM Connect (Device)
Option 2 (D-P-D-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Withings Body+ (Device)
Option 2 (D-P-D-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Hem-Col Capillary Blood Collection Device (Diagnostic Test)
Option 2 (D-P-D-P)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: MEMS (Medication Electronic Monitoring System) Cap (Device)
Option 3 (D-P-P-D)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Dapagliflozin 10mg Tab (Drug)
Option 3 (D-P-P-D)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Placebo (Drug)
Option 3 (D-P-P-D)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Withings BPM Connect (Device)
Option 3 (D-P-P-D)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Withings Body+ (Device)
Option 3 (D-P-P-D)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Hem-Col Capillary Blood Collection Device (Diagnostic Test)
Option 3 (D-P-P-D)
Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: MEMS (Medication Electronic Monitoring System) Cap (Device)
Option 4 (P-P-D-D)
Week 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Dapagliflozin 10mg Tab (Drug)
Option 4 (P-P-D-D)
Week 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Placebo (Drug)
Option 4 (P-P-D-D)
Week 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Withings BPM Connect (Device)
Option 4 (P-P-D-D)
Week 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Withings Body+ (Device)
Option 4 (P-P-D-D)
Week 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Hem-Col Capillary Blood Collection Device (Diagnostic Test)
Option 4 (P-P-D-D)
Week 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: MEMS (Medication Electronic Monitoring System) Cap (Device)
Option 5 (P-D-P-D)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Dapagliflozin 10mg Tab (Drug)
Option 5 (P-D-P-D)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Placebo (Drug)
Option 5 (P-D-P-D)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Withings BPM Connect (Device)
Option 5 (P-D-P-D)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Withings Body+ (Device)
Option 5 (P-D-P-D)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: Hem-Col Capillary Blood Collection Device (Diagnostic Test)
Option 5 (P-D-P-D)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out
干预措施: MEMS (Medication Electronic Monitoring System) Cap (Device)
Option 6 (P-D-D-P)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Dapagliflozin 10mg Tab (Drug)
Option 6 (P-D-D-P)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Placebo (Drug)
Option 6 (P-D-D-P)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Withings BPM Connect (Device)
Option 6 (P-D-D-P)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Withings Body+ (Device)
Option 6 (P-D-D-P)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: Hem-Col Capillary Blood Collection Device (Diagnostic Test)
Option 6 (P-D-D-P)
Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out
干预措施: MEMS (Medication Electronic Monitoring System) Cap (Device)
结局指标
主要结局
UACR response
时间窗: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
The individual response to the SGLT2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR)
次要结局
- Body weight response(Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.)
- Fasting plasma glucose response(Will be assessed within 6 months and reported within 2 years after conclusion of the study.)
- Systolic blood pressure response(Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.)
- eGFR response(Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.)