Clinical trial NCT05164523: The Effect of SGLT2 Inhibitors on Heart Rate Variability and BDNF Levels in Patients With Type 2 Diabetes
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 2 Diabetes
Heart Rate Variability
Keywords: type 2 diabetes
SGLT2 inhibitors
heart rate variability
sympathic activity
parasympathetic activity
Lead sponsor: Goztepe Training and Research Hospital
Sponsor class: OTHER
First posted: 2021-12-20
Enrollment: 64
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients who refer to a diabetes outpatients clinics to an university hospital

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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:

* 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

Primary outcomes:
measure: Heart rate variability parameters
timeFrame: Six months
measure: BDNF concentrations
timeFrame: Six months
Secondary outcomes:
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Istanbul Medeniyet University Goztepe Research and Training Hospital
Study officials:
affiliation: Istanbul Medeniyet University Goztepe Research and TRaining Hospital
name: Ayse N Erbakan, MD
role: PRINCIPAL_INVESTIGATOR
References: