Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03717207 |
| Other study ID # |
2210012018 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2010 |
| Est. completion date |
March 1, 2021 |
Study information
| Verified date |
April 2022 |
| Source |
University of Campania "Luigi Vanvitelli" |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Study hypothesis: cardiac autonomic dysfunction may affect vaso vagal syncope recurrences in
type 2 patients with diabetes vs. patients without diabetes.
Background: vaso vagal syncope and its recurrences may be due to alterations in autonomic
system function, that may be more frequent in diabetics. Heart rate variability (HRV) is a
valid test to study sympathetic and vaso vagal tone dysfunction. However, in this study
authors investigated the correlation between HRV alterations and diabetes in a population of
patients affected by syncope, and classified as vaso vagal syncope by Head Up Tilt Test (HUT)
exam. Secondly, authors assessed these alterations as causes of vaso vagal syncope recurring
at 12 months of follow up in type 2 patients with diabetes under sodium-glucose transporter 2
inhibitors (SGLT2-inhibitors) vs. other hypoglycemic drugs .. Materials and Methods: In a
multicenter study authors studied T2DM patients under SGLT2-I therapy (n 426) vs. those that
did not receive the SGLT2-I therapy (n 2195), and affectede by vaso vagal syncope. All
enrolled patients were in stable sinus rate before to perform ECG Holter, and the Head Up
Tilt Test (HUT). However, before to perform the HUT all patients performed a 24 hours ECG
Holter, to asses sinus rhythm , heart rate, and HRV. Then, these patients performed a
123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy to assess cardiac autonomic
dysfunction.
Moreover, authors performed a propensity score matching (PSM) analysis to evaluate 160
SGLT2-I users vs. 160 Non-SGLT2-I users' patients.
Description:
Vaso vagal syncope recurrence is a relevant clinical problem (1). In fact, despite the vaso
vagal syncope event is a transient loss of consciousness with rapid onset, short duration,
and spontaneous complete recovery after the event, it may be complicated by physical injury
(2). Conversely, the syncope recurrence rate is about 35%, and it causes a physical injury
until the 29% (3). In addition, the vaso vagal syncope has a frequency between 15% and 39%,
with annual number of episodes about 18.1-39.7 per 1000 patients, and an incidence of 6.2 per
1000 person-years, that grows up after 70 years of age with rate annual 19.5 per thousand
individuals after 80 years (3). The patients with type 2 diabetes mellitus (T2DM) represent a
percentage about the 30% of all the subjects with syncope (4). About the pathophysiology of
syncope a central role is played by autonomic nervous system (5). To date, the autonomic
nervous system regulates the hemodynamic stability by maintaining a stable blood pressure and
heart rate under normal and abnormal physiologic conditions (5). Consequently, the
dysfunction of this complex regulatory system, and of its interaction with sensor systems as
baroreceptors, mechanoreceptors, chemoreceptors, may alter the vascular reactivity, leading
to the clinical event and to future recurrences (5). Multiple factors affecting the autonomic
system balance may trigger and cause a syncope event, as the result of an inappropriate
response of the autonomic nervous system, with excessive vagal tone, and sympathetic tone
withdrawal (2). In this setting, authors may note the diabetes as a common cause of autonomic
system dysfunction (6). Moreover, T2DM may cause a severe form of autonomic system
dysfunction affecting the cardiac autonomic regulation, and named as cardiac autonomic
neuropathy (CAN), (6). Intriguingly, patients with diabetes experience a parasympathetic
denervation, with an early augmentation of sympathetic tone, then leading to impaired heart
rate variability, resting tachycardia, exercise intolerance, abnormal blood pressure
regulation, and orthostatic hypotension (7). In addition, in T2DM there is a compensatory
increase in the cardiac sympathetic tone in response to subclinical peripheral denervation
(7). However, the T2DM may be seen as a relevant risk factor and a trigger to alter the
autonomic system balance, and to cause vaso vagal syncope. In this context, the SGLT2-I are
hypoglycemic drugs that might modulate the systemic and cardiac sympathetic dysfunction. On
the other hand, the effects of the SGLT2-I therapy on the diabetic autonomic dysfunction and
the vaso vagal syncope recurrence at follow up is not well established. Moreover, the recent
studies cannot come to definitive conclusion about the impact of SGLT2-I on the vaso vagal
syncope events, and about its future recurrences in patients with type 2 diebetes mellitus
(T2DM). Conversely, heart rate variability (HRV) is a simple, reproducible and
well-recognized method for evaluating sympatho vagal activity (8, 9). In this setting, the
123I-MIBG is an imaging exam to evaluate the cardiac autonomic dysfunction. Indeed, the 123I
is an analogous of norepinephrine, and the entity of its myocardial captation is an index of
cardiac innervation.
However, in this study authors evaluated the autonomic dysfunction as alteration in HRV, and
123I-MIBG, and its relevance to cause vaso vagal syncope, and the vaso vagal syncope
recurrence in SGLT2-I users vs. Non-SGLT2-I users' patients with T2DM at 12 months of follow
up.
