Prognostic Predictors of Response to Hypoglycemic Therapy
2020년 2월 7일 업데이트: Conrady Alexandra, Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health
Search for Highly Specific Predictors of Response to Different Hypoglycemic Therapy for Cardiovascular Prognosis
This is a randomized controlled trial aimed to determine highly specific personified predictors of response to the therapy by different groups of hypoglycemic drugs (SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 receptor agonists, sulfonylureas) in patients with type 2 diabetes mellitus, develop an algorithm of personalized therapy based on them, design an organizational and methodological model for prevention of the cardiovascular complications, and create an automated decision-making system for therapy selection to reduce the incidence of cardiovascular events and related adverse outcomes compared to the traditional approach.
This is an interventional, randomized controlled trial, open-label study.
연구 개요
상세 설명
The study aims to determine highly specific personified predictors of response to the therapy by different groups of hypoglycemic drugs in patients with type 2 diabetes mellitus, to develop on their basis a mathematical model that allows to objectify the choice of therapy for each patient, and validate it in clinical practice with assessment of dynamic of cardiovascular risk markers (vascular wall condition, markers of fibrosis and inflammation, molecular-genetic markers of vascular damage, dynamic of intestinal microbiota, clinical outcomes, psychological parameters of quality of life, eating, treatment satisfaction) and pharmaco-economic component.
Patients with type 2 diabetes mellitus and non-target HbA1c will be randomized to receive antidiabetic drugs (SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 receptor agonists, sulfonylureas) in open prospective study according to: 1) standard recommendations; 2) predictors chosen with automated decision-making system developed on the literature analysis.
At baseline and 3, 6, 12, and 24 months into the study patients will be asked to complete the questionnaires on eating behavior, appetite, propensity to alcohol consumption, smoking, level of physical activity, general health condition, level of anxiety and depression, cognitive functions, adherence to treatment and treatment satisfaction.
At baseline and 3, 6, 12, and 24 months into the study there will be physical examination and laboratory tests, including: fasting and 1.5 hours post meal glucose, glycated hemoglobin, insulin with calculation of HOMA-IR index, indicators of lipid metabolism (total cholesterol, TG, LDL, calculation of HDL and VLDL), markers of kidney function (serum creatinine with GFR calculation, urine albumin-to-creatinine ratio), biochemical parameters of therapy safety (ALT, AST, bilirubin, uric acid, fibrinogen, alkaline phosphatase, amylase 5), levels of orexigenic / anorexigenic hormones (GLP1, GIP, ghrelin, leptin, glucagon, adiponectin, C-peptide).
The study will also include the evaluation of endothelial dysfunction (using EndoPAT 2000), state of the vascular wall (using the SphygmoCor), thickness of intima-media complex of carotid arteries, echocardiographic study, estimation of the global longitudinal strain (2-D Speckle-tracking echocardiographic analysis), MRI of the heart, biomarkers of inflammation (CRP level by the ultrasensitive method, adhesion molecules E-selectin and sICAM-1), markers of oxidative stress (myeloperoxidase, paraoxanase-1), markers of fibrosis (PICP, PIIINP, CITP, MMP / TIMP, TGF-β, galectin-3), markers of heart failure (NT-proBNP, sST2).
The investigators will conduct immunophenotyping of circulating progenitor cells (CD45 + / CD34 + / collagen-I +) by flow cytometry, and assess molecular-genetic markers of endothelial damage (microRNA-126, microRNA-21, microRNA-27, miRNA-125 and miRoRNA-155).
연구 유형
중재적
등록 (예상)
800
단계
- 4단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
- 이름: Alina Babenko, MD, PhD
- 전화번호: 0078127025586
- 이메일: alina_babenko@mail.ru
연구 장소
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Saint-Petersburg, 러시아 연방, 197143
- 모병
- Alina Babenko
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연락하다:
- Alina Babenko
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Male and female aged 17-70 years
- Type 2 diabetes mellitus with non-target HbA1c exciding less than 1% (<1%)
- Initiation of the treatment by SGLT- 2 inhibitors, dipeptidyl peptidase-4 inhibitors, GLP-1 analogues
- Stable hypoglycemic therapy for 12 weeks before enrollment
- Signed informed consent
Exclusion Criteria:
- Type 1 diabetes mellitus
- Recent acute coronary syndrome or acute disturbance of cerebral blood circulation (less than 2 months ago)
- Decompensation of chronic heart failure, chronic heart failure class IV (NYHA), acute heart failure
- Confirmed non-diabetic kidney disease (glomerulonephritis, pyelonephritis, amyloidosis)
- Chronic kidney disease requiring hemodialysis and/or urinary albumin concentration (morning spot) >1000 mg/L
- Regular nephrotoxic drugs intake (long-term intake of NSAIDs, aminoglycosides, sulfonamides, cyclosporine, lithium preparations)
- Anamnesis of malignancy.
- Diabetic foot ulcer and neuropathic osteoarthropathy
- Anamnesis of bariatric surgery or surgical interventions on the gastrointestinal tract leading to malabsorption.
- Treatment with drugs reducing body weight less than 3 months ago or any other drugs use that can lead to a change in body weight.
- Liver disorders with elevation of ALT/AST exceeding three-fold the upper limit of normal
- Immunosuppressive therapy or regular nonsteroidal anti-inflammatory drugs intake
- Change in the dosage of thyroid hormones less than 6 weeks ago.
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 기초 과학
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Treatment chosen by automated decision-making system
Group A: type 2 diabetic patients randomized to receive antidiabetic drugs according to predictors chosen with developed automated decision-making system: subgroup 1A- addition of vildagliptin 100 mg/day, subgroup 2A - addition of sitagliptin 100 mg/day, subgroup 3A- addition of dapagliflozin 10 mg/day, subgroup 4A- addition of empagliflozin 10 mg/day, subgroup 5A- addition of liraglutide 1,2-1,8 mg/day, subgroup 6A- addition of exenatide 20 μg/day, subgroup 7A - addition of glimepiride, subgroup 8A - addition of gliclazide.
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Addition of: 1A -vildagliptin 100 mg/day 2A - sitagliptin 100 mg/day, 3A- dapagliflozin 10 mg/day 4A- empagliflozin 10 mg/day 5A- liraglutide 1,2-1,8 mg/day 6A- exenatide 20 μg/day 7A - glimepiride 8A - gliclazide
Addition of:
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실험적: Treatment based on standard recommendations
Group B: type 2 diabetic patients randomized to receive antidiabetic drugs according to standard recommendations : subgroup 1B- addition of vildagliptin 100 mg/day, subgroup 2B - addition of sitagliptin 100 mg/day, subgroup 3B- addition of dapagliflozin 10 mg/day, subgroup 4B- addition of empagliflozin 10 mg/day, subgroup 5B- addition of liraglutide 1,2-1,8 mg/day, subgroup 6B- addition of exenatide 20 μg/day, subgroup 7B - addition of glimepiride, subgroup 8B - addition of gliclazide.
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Addition of: 1A -vildagliptin 100 mg/day 2A - sitagliptin 100 mg/day, 3A- dapagliflozin 10 mg/day 4A- empagliflozin 10 mg/day 5A- liraglutide 1,2-1,8 mg/day 6A- exenatide 20 μg/day 7A - glimepiride 8A - gliclazide
Addition of:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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HbA1c
기간: baseline and 3, 12, and 24 months after intervention
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Change from baseline in HbA1c level (%)
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baseline and 3, 12, and 24 months after intervention
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Body mass index
기간: baseline and 3, 12, and 24 months after intervention
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Change from baseline in body mass index (kg/m^2)
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baseline and 3, 12, and 24 months after intervention
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Estimated glomerular filtration rate
기간: baseline, 12 and 24 months after intervention
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Change from baseline in level of estimated glomerular filtration rate (ml/min/1.73
m^2)
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baseline, 12 and 24 months after intervention
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HOMA-IR index
기간: baseline, 6 and 12 months after intervention
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Change from baseline in level of HOMA-IR index (Homeostasis Model Assessment of Insulin Resistance) derived from the plasma insulin level (mIU/L) and plasma glucose level (mmol/L) of a participant: [(plasma insulin level) x (plasma glucose level)]/22.5,
where the value of HOMA-IR index > 2.0 suggests insulin resistance
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baseline, 6 and 12 months after intervention
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Urinary creatinine-adjusted excretion of albumin
기간: baseline, 12 and 24 months after intervention
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Change from baseline in level of urinary creatinine-adjusted excretion of albumin in morning spot urine samples (mg/mmol)
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baseline, 12 and 24 months after intervention
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Cardiovascular parameters of PAT and IMT
기간: baseline, 6 and 12 months after intervention
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Change from baseline in peripheral arterial tone by using EndoPAT 2000, the thickness of intima-media complex of carotid arteries (μm)
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baseline, 6 and 12 months after intervention
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LDL cholesterol
기간: baseline, 6 and 12 months after intervention
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Change from baseline in level of LDL cholesterol (mmol/L)
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baseline, 6 and 12 months after intervention
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Triglycerides
기간: baseline, 6 and 12 months after intervention
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Change from baseline in level of triglycerides (mmol/L)
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baseline, 6 and 12 months after intervention
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NT-proBNP
기간: baseline, 6 and 12 months after intervention
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Change from baseline in serum level of NT-proBNP (pmol/L)
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baseline, 6 and 12 months after intervention
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hsCRP
기간: baseline, 6 and 12 months after intervention
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Change from baseline in serum level of hsCRP ( mg/L)
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baseline, 6 and 12 months after intervention
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PAT
기간: baseline, 6 and 12 months after intervention
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Change from baseline in peripheral arterial tone by using EndoPAT 2000 (Ratio is created using the post and pre occlusion values)
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baseline, 6 and 12 months after intervention
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IMT
기간: baseline, 6 and 12 months after intervention
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Change from baseline in the thickness of intima-media complex of carotid arteries (μm)
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baseline, 6 and 12 months after intervention
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LV ejection fraction
기간: baseline, 6 and 12 months after intervention
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Change from baseline in ejection fraction (%) by echocardiography
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baseline, 6 and 12 months after intervention
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LV mass index
기간: baseline, 6 and 12 months after intervention
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Change from baseline in LV mass index (g/m^2) by echocardiography
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baseline, 6 and 12 months after intervention
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GLS by 2D-STE
기간: baseline, 6 and 12 months after intervention
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Change from baseline in global longitudinal strain by 2D Speckle-tracking echocardiography (%)
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baseline, 6 and 12 months after intervention
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Molecular-genetic markers of endothelial damage
기간: baseline, 6 and 12 months after intervention
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Change from baseline in serum level of microRNA-126, microRNA-21, microRNA-27, miRNA-125 and miRoRNA-155 (relative units)
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baseline, 6 and 12 months after intervention
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여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2017년 8월 1일
기본 완료 (예상)
2020년 3월 1일
연구 완료 (예상)
2020년 5월 1일
연구 등록 날짜
최초 제출
2018년 6월 8일
QC 기준을 충족하는 최초 제출
2019년 1월 14일
처음 게시됨 (실제)
2019년 1월 15일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2020년 2월 10일
QC 기준을 충족하는 마지막 업데이트 제출
2020년 2월 7일
마지막으로 확인됨
2020년 2월 1일
추가 정보
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