Acute Effects of SGLT2 Inhibition on Renal Oxygenation and Autonomic Function in Type 1 Diabetes
Status:
Completed
Trial end date:
2021-01-01
Target enrollment:
Participant gender:
Summary
Background: Inhibiting the sodium-glucose cotransporter-2 (SGLT2) has been observed to reduce
risk of cardiovascular events and kidney failure in type 2 diabetes. The exact mechanisms of
the beneficial effects of SGLT2 inhibition (SGLT2i) are still unknown. Kidney hypoxia has
been demonstrated in diabetic kidney disease and SGLT2i is thought to relieve hypoxia in the
kidneys. Mitochondrial dysfunction and autonomic dysfunction might also contribute to kidney
hypoxia.
Objective: The primary aim of the study is to assess the acute effects of SGLT2 inhibition on
parameters reflecting oxygenation and oxygen consumption of the human kidney in persons with
type 1 diabetes. Exploratory aims are to investigate acute changes in oxygen availability and
oxygen access to the kidneys after SGLT2i. This include measures of peripheral blood
oxygenation, mitochondrial function and autonomic function.
Methods: Acute intervention study with oral dapagliflozin given in two doses each of 50 mg or
matching placebo as intervention. Kidney oxygenation and perfusion parameters will be
assessed by blood-oxygen-dependant level magnetic resonance imaging. Mitochondrial function
will be assessed by extracellular flux analysis on lymphocytes. Autonomic function will be
assessed by measuring baroreflex sensitivity.
Design: Randomized, double blinded, placebo-controlled, cross-over intervention study.
Study population: Fifteen healthy controls are recruited by advertisement and 15 patients
with type 1 diabetes recruited from Steno Diabetes Center Copenhagen.
Endpoints: Primary end-point: Renal cortical and medullary oxygenation (T2*). Exploratory
end-points: Renal cortical and medullary perfusion, renal artery flow, renal oxygen
consumption, peripheral capillary oxygen saturation (SpO2), arterial oxygen partial pressure
(PaO2), arterial oxygen saturation (SaO2), lymphocyte mitochondrial function, baroreflex
sensitivity.
Timeframe: Inclusion of patients from January 2020. Last patient last visit January 2021.
Data analysis completed spring 2021, presentation autumn 2021 and publications Winter 2021.
Phase:
Phase 4
Details
Lead Sponsor:
Steno Diabetes Center Copenhagen
Collaborators:
Glostrup University Hospital, Copenhagen Novo Nordisk A/S