- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03804411
Prognostic Predictors of Response to Hypoglycemic Therapy
February 7, 2020 updated by: 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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
Detailed Description
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).
Study Type
Interventional
Enrollment (Anticipated)
800
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Alina Babenko, MD, PhD
- Phone Number: 0078127025586
- Email: alina_babenko@mail.ru
Study Locations
-
-
-
Saint-Petersburg, Russian Federation, 197143
- Recruiting
- Alina Babenko
-
Contact:
- Alina Babenko
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HbA1c
Time Frame: 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
Time Frame: 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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Estimated glomerular filtration rate
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 1, 2017
Primary Completion (Anticipated)
March 1, 2020
Study Completion (Anticipated)
May 1, 2020
Study Registration Dates
First Submitted
June 8, 2018
First Submitted That Met QC Criteria
January 14, 2019
First Posted (Actual)
January 15, 2019
Study Record Updates
Last Update Posted (Actual)
February 10, 2020
Last Update Submitted That Met QC Criteria
February 7, 2020
Last Verified
February 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 11/2017
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diabetes Mellitus, Type 2
-
SanofiCompletedType 1 Diabetes Mellitus-Type 2 Diabetes MellitusHungary, Russian Federation, Germany, Poland, Japan, United States, Finland
-
Mannkind CorporationTerminatedType 2 Diabetes Mellitus | Type 1 Diabetes MellitusUnited States
-
RWTH Aachen UniversityBoehringer IngelheimCompletedDiabetes Mellitus Type 2 (T2DM)Germany
-
University Hospital Inselspital, BerneCompletedType 2 Diabetes MellitusSwitzerland
-
India Diabetes Research Foundation & Dr. A. Ramachandran...CompletedTYpe 2 Diabetes MellitusIndia
-
Griffin HospitalCalifornia Walnut CommissionCompletedDIABETES MELLITUS TYPE 2United States
-
HighTide Biopharma Pty LtdRecruitingT2DM (Type 2 Diabetes Mellitus)China
-
AstraZenecaNot yet recruiting
-
Daewoong Pharmaceutical Co. LTD.Not yet recruitingT2DM (Type 2 Diabetes Mellitus)
-
Zhongda HospitalRecruitingType 2 Diabetes Mellitus (T2DM)China
Clinical Trials on Automatic system guided treatment
-
Seoul National University HospitalPhilips HealthcareCompletedHepatocellular Carcinoma
-
Yanqing LiCompletedEsophagogastroduodenoscopyChina
-
Lawson Health Research InstituteUnknownDepression | Quality of Life | Eye Diseases | AnxietyCanada
-
China Medical University, TaiwanUnknown
-
Hadassah Medical OrganizationShaare Zedek Medical CenterUnknownIntensive Care Patients on a VentilatorIsrael
-
Young-Hak Kim, MD, PhDRecruitingCoronary DiseaseKorea, Republic of
-
NovaShunt AGCompletedAscites | Congestive Heart FailureSweden
-
Capital Medical UniversityRecruitingCerebral Small Vessel DiseasesChina
-
Lawson Health Research InstituteUnknownAge-related Macular Degeneration | Low VisionCanada
-
Lawson Health Research InstituteUnknownDepression | Quality of Life | Glaucoma | AnxietyCanada