Prognostic Predictors of Response to Hypoglycemic Therapy
2020年2月7日 更新者：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.
調査の概要
詳細な説明
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).
研究の種類
介入
入学 (予想される)
800
段階
- フェーズ 4
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Alina Babenko, MD, PhD
- 電話番号：0078127025586
- メール：alina_babenko@mail.ru
研究場所
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Saint-Petersburg、ロシア連邦、197143
- 募集
- Alina Babenko
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コンタクト：
- Alina Babenko
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～70年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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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実験的：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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HbA1c
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Estimated glomerular filtration rate
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2017年8月1日
一次修了 (予想される)
2020年3月1日
研究の完了 (予想される)
2020年5月1日
試験登録日
最初に提出
2018年6月8日
QC基準を満たした最初の提出物
2019年1月14日
最初の投稿 (実際)
2019年1月15日
学習記録の更新
投稿された最後の更新 (実際)
2020年2月10日
QC基準を満たした最後の更新が送信されました
2020年2月7日
最終確認日
2020年2月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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