Type 2 DiabetesNCT05164523
The Effect of SGLT2 Inhibitors on Heart Rate Variability and BDNF Levels in Patients With Type 2 Diabetes
An observational study of Type 2 Diabetes and Heart Rate Variability, run by Goztepe Training and Research Hospital at 1 site in Turkey (Türkiye).
Trial summary
Cardiac autonomic neuropathy (CAN) in diabetic patients is an indicator of autonomic nervous system dysfunction and is an important marker for cardiovascular events. Very promising results have been obtained with SGLT2 inhibitors in both cardiac and renal outcomes. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Type 2 Diabetes, Heart Rate Variability
- What is being tested?
- 24-hour rhythm Holter and 36 item Short Form Survey (SF-36)
- How many people
- 64 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Mar 2021to 30 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients who refer to a diabetes outpatients clinics to an university hospital
Who may be able to join
- giving consent
- being 30 years old or older
- HbA1c concentrations between 6.5% and 8%
- using metformin as a single agent for at least 3 months
- diabetes age <10 years
- Exclusion Criteria: existence of one of the listed conditions:
Show all 21Show fewer
- having uncontrolled hypothyroidism, hyperthyroidism, or other diseases that may affect cognitive functions
- ketoacidosis or coma
- cerebrovascular disease or psychiatric disorder
- mental retardation, psychosis, dementia, brain trauma, epilepsy and other cerebral diseases
- alcohol or other substance abuse
- hearing loss
- Presence of diseases that will affect cognitive function such as chronic inflammatory diseases and respiratory system diseases
- chronic kidney failure (GFR <45)
- sleep apnea syndrome
- malignancy
- using a sulfonylurea or glinide
- using beta blocker or non-dihydropyridine group calcium antagonists
- diabetic autonomous neuropathy
- atrial fibrillation
- an acute coronary event within the last 3 months
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Istanbul Medeniyet University Goztepe Research and Training Hospital
Istanbul
About this study
Official title: The Effect of SGLT2 Inhibitors on Heart Rate Variability, Sympathetic and Parasympathetic Activity and a Neuroinflammatory Biomarker, Brain-Derived Neurotrophic Factor Levels in Patients With Type 2 Diabetes
Cardiac autonomic neuropathy (CAN) in diabetic patients is an indicator of autonomic nervous system dysfunction and is an important marker for cardiovascular events. Very promising results have been obtained with SGLT2 inhibitors in both cardiac and renal outcomes. The aim is to examine the effects of SGLT2 inhibitor use on cardiac autonomic neuropathy, heart rate variability, sympathetic and parasympathetic nervous system parameters, and their relationship with BDNF levels, one of the neuroinflammatory markers.
Read the detailed description
Cardiac autonomic neuropathy (CAN) in diabetic patients is an indicator of autonomic nervous system dysfunction and is an important marker for cardiovascular events. Five-year mortality rates of diabetic patients with CAN are significantly higher than those without. Although there are various methods, primarily scintigraphic and pharmacological tests, to evaluate CAN, the practical use of these methods remains limited. In recent years, heart rate recovery (HRR) and heart rate variability (HRV) have been increasingly used as simple, inexpensive, and non-invasive methods to evaluate the status of heart sympathetic and vagus nerve functions. Values obtained as a result of 24-hour rhythm Holter provide the measurement of sympathetic and parasympathetic activity. While a significant relationship was observed between blood glucose levels and HRV in previous studies, no relationship was found between HbA1c levels and HRV.
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with growth factor properties. Studies with SGLT2 inhibitors have shown a decrease in HbA1c values, weight loss, and a decrease in both systolic and diastolic blood pressure. Very promising results have been obtained with SGLT2 inhibitors in both cardiac and renal outcomes. As a result of these data, these medications are recommended as drugs that should be used in the foreground following metformin, especially in diabetic patients with cardiac and renal diseases. In the study of Shimuz et al. in which the effects of empagliflozin and placebo on heart rate variability were compared in patients with acute myocardial infarction, HRV improved significantly with the use of empagliflozin in the early period. A study examining the effects of empagliflozin use on HRV in patients with type 2 diabetes is still ongoing. Apart from these 2 studies, no study was found in the literature.
The aim of this study is to examine the effects of SGLT2 inhibitor use on cardiac autonomic neuropathy, heart rate variability, sympathetic and parasympathetic nervous system parameters, and their relationship with BDNF levels, one of the neuroinflammatory markers.
- Conditions
- Type 2 Diabetes, Heart Rate Variability
- Being tested
- 24-hour rhythm Holter, 36 item Short Form Survey (SF-36)
- Keywords
- type 2 diabetes, SGLT2 inhibitors, heart rate variability, sympathic activity, parasympathetic activity
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
24-hour rhythm HolterDiagnostic test
Before starting their newly prescribed medication, the investigators will apply 24-hour rhythm Holter and repeat it at the end of the trial.
36 item Short Form Survey (SF-36)Diagnostic test
Also called SF-36
Before starting their newly prescribed medication, the investigators will apply SF-36 survey and repeat it at the end of the trial.
| Study group | Role | What they receive |
|---|---|---|
| Patients with type 2 diabetes treated with SGLT2 inhibitors | metformin using patients with type 2 diabetes who were recently prescribed an SGLT2 inhibitor Receives: Diagnostic Test: 24-hour rhythm Holter; Diagnostic Test: 36 item Short Form Survey (SF-36) | |
| Patients with type 2 diabetes treated with other oral agents | metformin using patients with type 2 diabetes who were recently prescribed a pre-defined antidiabetic medication other than SGLT2 inhibitors Receives: Diagnostic Test: 24-hour rhythm Holter; Diagnostic Test: 36 item Short Form Survey (SF-36) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate variability parameters
The investigators will evaluate the effects of SGLT2 inhibitor use on heart rate variability derived from 24-hour rhythm Holter compared with other antidiabetic medications.
Measured: Six months
BDNF concentrations
The investigators will observe the effects of SGLT2 inhibitors and other oral antidiabetic agents on BDNF levels in type 2 diabetic patients.
Measured: Six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2021
- Study start1 Mar 2021
- Primary completion21 Dec 2022
- Study completion30 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Goztepe Training and Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ayse N Erbakan, Goztepe Training and Research Hospital
- Investigators
- Ayse N Erbakan, MD, Principal investigator, Istanbul Medeniyet University Goztepe Research and TRaining Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05164523
- Sponsor's protocol ID
- Heart Rate Variability-BDNF
- Status last verified
- Sep 2023
- First submitted
- 17 Oct 2021
- Last updated
- 5 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of SGLT2 Inhibitors on Heart Rate Variability, Sympathetic and Parasympathetic Activity and a Neuroinflammatory Biomarker, Brain-Derived Neurotrophic Factor Levels in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05164523
- Acronym / sponsor ID
- Heart Rate Variability-BDNF
- Conditions
- Type 2 Diabetes, Heart Rate Variability
- Keywords
- type 2 diabetes, SGLT2 inhibitors, heart rate variability, sympathic activity, parasympathetic activity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Goztepe Training and Research HospitalUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 21 Dec 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 20 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cardiac autonomic neuropathy (CAN) in diabetic patients is an indicator of autonomic nervous system dysfunction and is an important marker for cardiovascular events. Very promising results have been obtained with SGLT2 inhibitors in both cardiac and renal outcomes. The aim is to examine the effects of SGLT2 inhibitor use on cardiac autonomic neuropathy, heart rate variability, sympathetic and parasympathetic nervous system parameters, and their relationship with BDNF levels, one of the neuroinflammatory markers.
Detailed description
Cardiac autonomic neuropathy (CAN) in diabetic patients is an indicator of autonomic nervous system dysfunction and is an important marker for cardiovascular events. Five-year mortality rates of diabetic patients with CAN are significantly higher than those without. Although there are various methods, primarily scintigraphic and pharmacological tests, to evaluate CAN, the practical use of these methods remains limited. In recent years, heart rate recovery (HRR) and heart rate variability (HRV) have been increasingly used as simple, inexpensive, and non-invasive methods to evaluate the status of heart sympathetic and vagus nerve functions. Values obtained as a result of 24-hour rhythm Holter provide the measurement of sympathetic and parasympathetic activity. While a significant relationship was observed between blood glucose levels and HRV in previous studies, no relationship was found between HbA1c levels and HRV.
Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family with growth factor properties. Studies with SGLT2 inhibitors have shown a decrease in HbA1c values, weight loss, and a decrease in both systolic and diastolic blood pressure. Very promising results have been obtained with SGLT2 inhibitors in both cardiac and renal outcomes. As a result of these data, these medications are recommended as drugs that should be used in the foreground following metformin, especially in diabetic patients with cardiac and renal diseases. In the study of Shimuz et al. in which the effects of empagliflozin and placebo on heart rate variability were compared in patients with acute myocardial infarction, HRV improved significantly with the use of empagliflozin in the early period. A study examining the effects of empagliflozin use on HRV in patients with type 2 diabetes is still ongoing. Apart from these 2 studies, no study was found in the literature.
The aim of this study is to examine the effects of SGLT2 inhibitor use on cardiac autonomic neuropathy, heart rate variability, sympathetic and parasympathetic nervous system parameters, and their relationship with BDNF levels, one of the neuroinflammatory markers.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with type 2 diabetes treated with SGLT2 inhibitors | – | Diagnostic Test: 24-hour rhythm Holter, Diagnostic Test: 36 item Short Form Survey (SF-36)metformin using patients with type 2 diabetes who were recently prescribed an SGLT2 inhibitor |
| Patients with type 2 diabetes treated with other oral agents | – | Diagnostic Test: 24-hour rhythm Holter, Diagnostic Test: 36 item Short Form Survey (SF-36)metformin using patients with type 2 diabetes who were recently prescribed a pre-defined antidiabetic medication other than SGLT2 inhibitors |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients who refer to a diabetes outpatients clinics to an university hospital
Key inclusion criteria (21 listed)
- giving consent
- being 30 years old or older
- HbA1c concentrations between 6.5% and 8%
- using metformin as a single agent for at least 3 months
- diabetes age <10 years
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 24-hour rhythm HolterBefore starting their newly prescribed medication, the investigators will apply 24-hour rhythm Holter and repeat it at the end of the trial. | Diagnostic test | Patients with type 2 diabetes treated with SGLT2 inhibitors, Patients with type 2 diabetes treated with other oral agents |
| 36 item Short Form Survey (SF-36)Also: SF-36Before starting their newly prescribed medication, the investigators will apply SF-36 survey and repeat it at the end of the trial. | Diagnostic test | Patients with type 2 diabetes treated with SGLT2 inhibitors, Patients with type 2 diabetes treated with other oral agents |
Primary outcome
Heart rate variability parameters
Time frame: Six months
The investigators will evaluate the effects of SGLT2 inhibitor use on heart rate variability derived from 24-hour rhythm Holter compared with other antidiabetic medications.
BDNF concentrations
Time frame: Six months
The investigators will observe the effects of SGLT2 inhibitors and other oral antidiabetic agents on BDNF levels in type 2 diabetic patients.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ayse N Erbakan, MD principal investigator
Istanbul Medeniyet University Goztepe Research and TRaining Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 2 Diabetes and Heart Rate Variability, run by Goztepe Training and Research Hospital at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heart rate variability parameters (time frame: Six months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2023.