Effect of SGLT-2 Inhibitor Dapagliflozin on Glycemic Variability in Patients With Diabetes Mellitus Type 2

March 24, 2016 updated by: Research Clinical Centre of the Russian Railways, JSC

Randomized, Open Prospective Study of the Effect of SGLT-2 Inhibitor Dapagliflozin on Glycemic Variability in Patients With Diabetes Mellitus Type 2

This study will test the hypothesis that early use of combination therapy with dapagliflozin and metformin will provide good glycemic control with low glycemic variability and without hypoglycemic episodes, and will be better tolerated than up-titration of metformin monotherapy. The study will also correlate these benefits with glycated hemoglobin.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Type 2 diabetes is a progressive, chronic metabolic disease characterized by hyperglycemia. Despite therapeutic advances, the incidence and prevalence of diabetes continue to surge. Worldwide, the number of individuals with diabetes is projected to rise from 366 million in 2011 to 552 million by 2030, which is the equivalent of approximately three new cases being diagnosed every 10 seconds. Type 2 diabetes doubles the risk of cardiovascular disease, and macrovascular complications (myocardial infarction and stroke) are a common cause of death in patients with type 2 diabetes. The U.K. Prospective Diabetes Study showed that every 1% absolute decline in mean A1C was associated with a 37% reduction in the risk of microvascular complications and a 21% reduction in the risk of any diabetes-related complication or death. Diabetes also exacts a tremendous economic burden. Meeting treatment goals is elusive for many people with diabetes. Data from the National Health and Nutrition Examination Survey from 2003 to 2006 showed that only 57.1% of adults with diagnosed diabetes achieved an A1C < 7%, 45.5% had a blood pressure level < 130/80 mmHg, and 46.5% had an LDL cholesterol level < 100 mg/dl. Only 12.2% of people with diabetes reached all three goals. Treatment of Type 2 diabetes is not limited to just glycaemic control. Rather, the proper management of hyperglycaemia, weight, blood pressure, and lipids can have benefits in terms of slowing the progression of Type 2 diabetes, decreasing the risk of CV disease, and improving overall health.Current antihyperglycaemic treatments are predominantly insulin-dependent. These treatments can effectively manage HbA1c, and treatment may be influenced by the patient's comorbidities and any potential treatment-related adverse events. However, as Type 2 diabetes progresses, regimens need to be modified to compensate for declining beta-cell function and decreasing insulin sensitivity. On this basis,the EASD/ADA guidelines suggest following a treatment pathway that has well validated therapies at it's core.Of the many comorbid conditions described, excess weight is especially important, not only because of the increased disease risk, but also for the management of blood pressure and lipids. Consequently, AACE/ACE algorithms give priority to those regimens that have the added benefit of minimising hypoglycaemic events and weight gain.In addition, while antidiabetic treatments tend to focus on insulin-dependent mechanisms in organs such as the liver and pancreas, it should not be forgotten that the kidneys also have a role in maintaining glucose homeostasis There are multiple barriers to achieving optimal glycemic control. Current medications for type 2 diabetes have potential adverse effects; for example, can cause hypoglycemia and weight gain. Hypoglycaemia is a limiting factor in the glycaemic management of patients with advanced Type 2 diabetes.Most often hypoglycaemia is associated with mild to severe neurologic symptoms, and in some cases it can result in death. Additionally, the risk of cardiac ischaemia is increased in Type 2 diabetes patients with symptomatic or asymptomatic hypoglycaemia compared with patients with hyperglycaemia or stable normoglycaemia. The risk of hypoglycaemia increases with advancing age, polypharmacy, later stages of disease, and intensive antihyperglycaemic treatment with certain drugs, such as sulphonylureas. Intensive treatment (target HbA1c<7.0%) results in a greater number of patients experiencing severe hypoglycaemic events (3-21%) compared with conventional treatment (target HbA1c ≥7.0%; 2-10%), although intensive therapy may have a greater beneficial effect in terms of a decreased risk of microvascular disease. As a result, hypoglycaemia is one of several factors, including weight gain and increases in CV disease-related and overall mortality, that may limit the microvascular benefits of intensive therapy. Thus, the search continues for novel therapeutic agents that can help patients avoid these limiting side effects while providing glycemic control.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 125993
        • Research Clinical Centre of the Russian Railways, JSC

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 74 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

The subject population that will be observed in the study, must fulfil all of the following criteria:

  1. Signed informed consent.
  2. Written informed consent by women of childbearing age to interception during study participation period, with determination of level of chorionic gonadotropic hormone by the pregnancy test, prior to study enrollment.
  3. Age >=18 - 74 years.
  4. eGFR >=60 mL/min/1.73 m2 by MDRD formula.
  5. BMI <40 kg / m2
  6. C-peptide >= 1 ng/ml
  7. HbA1c 7 - 9% both included
  8. Stabile 1000 mg dose of Metformin daily for at least 8 weeks prior to enrollment

Exclusion criteria

  1. The presence of absolute contraindications to therapy by SGLT-2 inhibitor Dapagliflozin:

    1.1. Individual idiosyncrasy of any drug component.

    1.2. Type 1 diabetes.

    1.3. Diabetic ketoacidosis.

    1.4. Renal disease, medium to severe (eGFR <60 ml/min /1.73m2 by MDRD formula) or end-stage renal failure.

    1.5.Hereditary lactose intolerance, lactase deficiency, and glucose and galactose intolerance.

    1.6. Pregnancy and breast-feeding.

    1.7. Children under 18 years of age.

    1.8. Patients receiving loop diuretics or with reduced volume of blood circulation, such as a result of acute diseases (e.g. gastrointestinal problems).

    1.9. Elderly patients aged 75 years and older.

  2. A history of moderate or severe congestive heart failure (New York Heart Association [NYHA] Class III or IV) within 3 months prior to the screening visit
  3. Increased liver transaminases ALT and/or AST more than 3 times higher than normal.
  4. Any condition that in the opinion of the PI confound the evaluation and interpretation of efficacy and or safety data. Significant medical or psychological condition that, in the opinion of the Investigator, would compromise the patient's safety or successful participation in the study.

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

  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Metformin & Dapagliflozin
Metformin stable dose tablets and Dapagliflozin 10 mg tablets by mouths, once daily in morning for 3 months
Drug: Metformin
Metformin tablets 1000 mg
Other Names:
  • GLUCOPHAGE
Drug: Dapagliflozin
Dapagliflozin 10 mg tablets
Other Names:
  • FORXIGA
  • FARXIGA
ACTIVE_COMPARATOR: Metformin up-titration
Metformin tablets up-titration by mouths, for 3 months
Drug: Metformin
Metformin tablets 1000 mg
Other Names:
  • GLUCOPHAGE
Drug: Metformin up-titration

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Dynamics (delta from the baseline) of blood glucose variability - integral index of glycemia (LBGI-HBGI) after 3 months of therapy
Time Frame: 3 months
3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Dynamics (delta from the baseline or % decrease of blood glucose level) of blood glucose variability (ADRR) after 3 months of therapy
Time Frame: 3 months
3 months
Dynamics of MAGE after 3 months of therapy
Time Frame: 3 months
3 months
Dynamic of glycaemia parameters: % of normoglycemia time after 3 months of therapy
Time Frame: 3 months
3 months
Dynamic of glycaemia parameters: % of hyperglycemia time after 3 months of therapy
Time Frame: 3 months
3 months
Dynamic of glycaemia parameters: % of hypoglycemia time after 3 months of therapy
Time Frame: 3 months
3 months
Dynamics of HbA1c (%) from baseline after 3 months of therapy
Time Frame: 3 months
3 months
Percentage of diabetes mellitus patients achieved individual target HbA1c
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Research Clinical Centre of the Russian Railways, JSC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alexander Ametov, prof., MD, Research Clinical Center of the Russian Railways, JSC

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2016

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2016

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 9, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2016

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ESR-15-11023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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.

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