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Prognostic Predictors of Response to Hypoglycemic Therapy

7 februari 2020 bijgewerkt door: 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.

Studie Overzicht

Toestand

Onbekend

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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).

Studietype

Ingrijpend

Inschrijving (Verwacht)

800

Fase

  • Fase 4

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • Russische Federatie
      • Saint-Petersburg, Russische Federatie, 197143
        • Werving
        • Alina Babenko
        • Contact:
          • Alina Babenko

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 70 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. Male and female aged 17-70 years
  2. Type 2 diabetes mellitus with non-target HbA1c exciding less than 1% (<1%)
  3. Initiation of the treatment by SGLT- 2 inhibitors, dipeptidyl peptidase-4 inhibitors, GLP-1 analogues
  4. Stable hypoglycemic therapy for 12 weeks before enrollment
  5. Signed informed consent

Exclusion Criteria:

  1. Type 1 diabetes mellitus
  2. Recent acute coronary syndrome or acute disturbance of cerebral blood circulation (less than 2 months ago)
  3. Decompensation of chronic heart failure, chronic heart failure class IV (NYHA), acute heart failure
  4. Confirmed non-diabetic kidney disease (glomerulonephritis, pyelonephritis, amyloidosis)
  5. Chronic kidney disease requiring hemodialysis and/or urinary albumin concentration (morning spot) >1000 mg/L
  6. Regular nephrotoxic drugs intake (long-term intake of NSAIDs, aminoglycosides, sulfonamides, cyclosporine, lithium preparations)
  7. Anamnesis of malignancy.
  8. Diabetic foot ulcer and neuropathic osteoarthropathy
  9. Anamnesis of bariatric surgery or surgical interventions on the gastrointestinal tract leading to malabsorption.
  10. 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.
  11. Liver disorders with elevation of ALT/AST exceeding three-fold the upper limit of normal
  12. Immunosuppressive therapy or regular nonsteroidal anti-inflammatory drugs intake
  13. Change in the dosage of thyroid hormones less than 6 weeks ago.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Enkel

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Geneesmiddel: Automatic system guided treatment
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
Geneesmiddel: Standard treatment

Addition of:

  1. B -vildagliptin 100 mg/day
  2. B - sitagliptin 100 mg/day,
  3. B- dapagliflozin 10 mg/day
  4. B- empagliflozin 10 mg/day
  5. B- liraglutide 1,2-1,8 mg/day
  6. B- exenatide 20 μg/day
  7. B - glimepiride
  8. B - gliclazide
Experimenteel: 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.
Geneesmiddel: Automatic system guided treatment
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
Geneesmiddel: Standard treatment

Addition of:

  1. B -vildagliptin 100 mg/day
  2. B - sitagliptin 100 mg/day,
  3. B- dapagliflozin 10 mg/day
  4. B- empagliflozin 10 mg/day
  5. B- liraglutide 1,2-1,8 mg/day
  6. B- exenatide 20 μg/day
  7. B - glimepiride
  8. B - gliclazide

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
HbA1c
Tijdsspanne: 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
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Estimated glomerular filtration rate
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Federal State Budgetary Institution, V. A. Almazov Federal North-West Medical Research Centre, of the Ministry of Health

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

1 augustus 2017

Primaire voltooiing (Verwacht)

1 maart 2020

Studie voltooiing (Verwacht)

1 mei 2020

Studieregistratiedata

Eerst ingediend

8 juni 2018

Eerst ingediend dat voldeed aan de QC-criteria

14 januari 2019

Eerst geplaatst (Werkelijk)

15 januari 2019

Updates van studierecords

Laatste update geplaatst (Werkelijk)

10 februari 2020

Laatste update ingediend die voldeed aan QC-criteria

7 februari 2020

Laatst geverifieerd

1 februari 2020

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 11/2017

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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