- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT03804411
Prognostic Predictors of Response to Hypoglycemic Therapy
7. Februar 2020 aktualisiert von: 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.
Studienübersicht
Status
Unbekannt
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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).
Studientyp
Interventionell
Einschreibung (Voraussichtlich)
800
Phase
- Phase 4
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienkontakt
- Name: Alina Babenko, MD, PhD
- Telefonnummer: 0078127025586
- E-Mail: alina_babenko@mail.ru
Studienorte
-
-
-
Saint-Petersburg, Russische Föderation, 197143
- Rekrutierung
- Alina Babenko
-
Kontakt:
- Alina Babenko
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 70 Jahre (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
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.
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Grundlegende Wissenschaft
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Single
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Experimental: 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.
|
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:
|
Experimental: 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.
|
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:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
HbA1c
Zeitfenster: baseline and 3, 12, and 24 months after intervention
|
Change from baseline in HbA1c level (%)
|
baseline and 3, 12, and 24 months after intervention
|
Body mass index
Zeitfenster: baseline and 3, 12, and 24 months after intervention
|
Change from baseline in body mass index (kg/m^2)
|
baseline and 3, 12, and 24 months after intervention
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
---|---|---|
Estimated glomerular filtration rate
Zeitfenster: baseline, 12 and 24 months after intervention
|
Change from baseline in level of estimated glomerular filtration rate (ml/min/1.73
m^2)
|
baseline, 12 and 24 months after intervention
|
HOMA-IR index
Zeitfenster: baseline, 6 and 12 months after intervention
|
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
|
baseline, 6 and 12 months after intervention
|
Urinary creatinine-adjusted excretion of albumin
Zeitfenster: baseline, 12 and 24 months after intervention
|
Change from baseline in level of urinary creatinine-adjusted excretion of albumin in morning spot urine samples (mg/mmol)
|
baseline, 12 and 24 months after intervention
|
Cardiovascular parameters of PAT and IMT
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in peripheral arterial tone by using EndoPAT 2000, the thickness of intima-media complex of carotid arteries (μm)
|
baseline, 6 and 12 months after intervention
|
LDL cholesterol
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in level of LDL cholesterol (mmol/L)
|
baseline, 6 and 12 months after intervention
|
Triglycerides
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in level of triglycerides (mmol/L)
|
baseline, 6 and 12 months after intervention
|
NT-proBNP
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in serum level of NT-proBNP (pmol/L)
|
baseline, 6 and 12 months after intervention
|
hsCRP
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in serum level of hsCRP ( mg/L)
|
baseline, 6 and 12 months after intervention
|
PAT
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in peripheral arterial tone by using EndoPAT 2000 (Ratio is created using the post and pre occlusion values)
|
baseline, 6 and 12 months after intervention
|
IMT
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in the thickness of intima-media complex of carotid arteries (μm)
|
baseline, 6 and 12 months after intervention
|
LV ejection fraction
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in ejection fraction (%) by echocardiography
|
baseline, 6 and 12 months after intervention
|
LV mass index
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in LV mass index (g/m^2) by echocardiography
|
baseline, 6 and 12 months after intervention
|
GLS by 2D-STE
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in global longitudinal strain by 2D Speckle-tracking echocardiography (%)
|
baseline, 6 and 12 months after intervention
|
Molecular-genetic markers of endothelial damage
Zeitfenster: baseline, 6 and 12 months after intervention
|
Change from baseline in serum level of microRNA-126, microRNA-21, microRNA-27, miRNA-125 and miRoRNA-155 (relative units)
|
baseline, 6 and 12 months after intervention
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
1. August 2017
Primärer Abschluss (Voraussichtlich)
1. März 2020
Studienabschluss (Voraussichtlich)
1. Mai 2020
Studienanmeldedaten
Zuerst eingereicht
8. Juni 2018
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
14. Januar 2019
Zuerst gepostet (Tatsächlich)
15. Januar 2019
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
10. Februar 2020
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
7. Februar 2020
Zuletzt verifiziert
1. Februar 2020
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- 11/2017
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Nein
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
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