Multifactorial Intervention to Reduce Cardiac and Renal Oxygen Need in Type 1 Diabetes (the MICRON Study) - A Steno 1 Substudy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 10
- 主要终点
- Myocardial oxygen consumption
研究概览
简要总结
The goal of this observational study is to compare cardiac and renal oxygen consumption among subjects with type 1 diabetes treated with either multifactorial intervention or according to the current standard care. Participants are recruited from a main study /the Steno1 study) responsible for the intervention.
The main questions it aims to answer are if a multifactorial intervention in subjects with type 1 diabetes targeting cardiovascular and renal risk factors, will reduce cardiac and renal oxygen demand.
Participants will undergo the following examinations at 0-month, 6-month, and 24-month after enrolling in the main study:
- Measurement of cardiac and real oxygen consumption ([11C]acetate PET/CT-scan)
- Measurement of kidney function ([99mTc]DTPA GFR measurement)
- Measurement of markers of heart and kidney disease in blood and urine samples.
详细描述
In the MICRON study we will recruit participants from the ongoing CTIS approved Steno 1 study which is a prospective, cluster-randomized multicentre trial of 2000 persons with T1D. The Steno 1 study evaluates cardiovascular and renal effects of a multifactorial intervention vs. standard clinical care in subjects with type 1 diabetes (T1D) and established diabetic kidney disease (DKD), cardiovascular disease (CVD), heart failure, obesity or a >10% 5-year CVD risk using the Steno Risk Engine. The multifactorial intervention includes ambitious blood pressure and lipid targets as well as individualised pharmacological intervention with semglutide, sotagliflozin, and/or finerenone.
For the MICRON study we will recruit 20 persons from the ongoing Steno 1 study receiving multifactorial intervention as well as 20 persons from the Steno 1 study receiving standard care. No additional intervention is used for the MICRON study.
In the MICRON study each participant will undergo both [¹¹C]acetate PET/CT and [⁹⁹mTc]DTPAGFR measurements at baseline (inclusion) and again after 6 and 24 months of treatment (multifactorial intervention vs. standard care). At each of the three visits, blood and urine samples will be collected, along with anthropometric measurements.
The primary outcome variables, myocardial and renal oxygen consumption, will be assessed using [¹¹C]acetate PET/CT using a long axial field-of-view (LAFOV) PET scanner. Given that renal oxygen consumption is influenced by glomerular filtration rate (GFR), we will use [⁹⁹mTc]DTPA to accurately measure and account for variations in GFR when assessing renal oxygen consumption.
Three additional work packages WP2, WP3 and WP4 are to be conducted in collaboration with Steno Diabetes Centre Copenhagen, Monash University, Melbourne, Australia and the Department of Biomedicine, Aarhus University, Aarhus, Denmark investigating: WP2 Fibrosis, WP3 Oxidative stress and inflammation and WP4 Urinary extracellular vesicle proteomics.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Steno 1 inclusion criteria:
- •Male or female persons ≥40 years old with T1D (diagnosis before age 30 with insulin from onset or if diagnosis after 30 years of age insulin from onset and DKA or positive autoantibodies (in accordance with local guidelines), or confirmed, at the investigator's discretion by the available medical records) during >10 years.
- •Presence of chronic kidney disease (UACR >30 mg/g or eGFR < 60 ml/min/1.73 m2) OR history of ischemic heart disease (previous myocardial infarction, stroke or angina) OR history of heart failure OR obesity grade 2 and 3 (BMI>35 kg/m2) OR 5-year CVD risk >10% according to Steno Type 1 Risk Engine.
- •Fertile females must use highly efficient chemical, hormonal and mechanical contraceptives during the whole study and at least 2 months after cessation of study drug. The following contraceptive methods are approved: IUD or hormonal contraception that inhibits ovulation, i.e. pills, implantations, transdermal patches, vaginal ring or depot injection. Alternatively, be in menopause (i.e. must not have had regular menstrual bleeding for at least one year), have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least 12 months prior to screening.
- •Ability to communicate with the investigator and understand informed consent.
- •Given written informed consent.
排除标准
- •Type 2 Diabetes, Maturity-onset diabetes of the young (MODY), secondary diabetes.
- •History of pancreatitis.
- •Body mass index < 18.5 kg/m2
- •Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods.
- •Known or suspected abuse of alcohol or recreational drugs.
- •Participant in another drug-intervention study.
- •Chronic Kidney Disease stage
- •Additional exclusion criteria in the MICRON study:
- •Active malignant disease
- •Use of study drugs (SGLT inhibitors, GLP-1 RA, or finererone) at inclusion.
研究组 & 干预措施
Intervention group in the Steno 1 study
Receiving the intensive treatment therapy in the Steno 1 Study. This consists of more ambitious blood pressure and lipid targets as well as individualised pharmacological intervention with GLP1 receptor agonist (semglutide), dual SGLT-1/2 inhibitor (sotagliflozin), and/or nonsteroidal mineralocorticoid receptor antagonist (finerenone).
Control group in the Steno 1 study.
Receiving standart care in the Steno 1 Study.
结局指标
主要结局
Myocardial oxygen consumption
时间窗: At baseline (0 month), at 6 months and 24 months.
Measured by \[11C\]acetate PET/CT Unit: volumen pr mass pr time
Renal oxygen consumption
时间窗: At baseline (0 month), at 6 months and 24 months.
Measured by \[11C\]acetate PET/CT Unit: volumen pr mass pr time
次要结局
- Myocardial external efficiency(At baseline (0 month), at 6 months and 24 months.)
- Myocardial perfusion(At baseline (0 month), at 6 months and 24 month.)
- Renal perfusion(At baseline (0 month), at 6 months and 24 months.)
- Amount of markers for oxidative stress and inflammation(Samples collected at baseline (0 month), at 6 months and 24 months.)
- Amount of markers for renal fibrosis(Samples collected at baseline (0 month), at 6 months and 24 months.)
- Urinary extracellular vesicle(On urine samples collected at baseline (0 month), at 6 months and 24 months. Differential protein abundance is assessed longitudinally (baseline vs 6 and 24 months) and cross-sectionally between treatments at matched time points.)
- Glomerular filtration rate(At baseline (0 month), at 6 months and 24 months.)
- Urine albumin-creatinine ratio(At baseline (0 month), at 6 months and 24 months. Moreover, results from in-clinic laboratory assessments will be collected during the study period if available.)