Acute Effects of GLP-1 on Renal Hemodynamics

The GLP-1-mediated Gut-kidney Axis Clinical Trial

— GLP1RRBF  

Official title:

Acute Effects of GLP-1 on Renal Hemodynamics: Simultaneous Perfusion and Oxygenation Measurements in Cortex and Medulla Using Magnetic Resonance Imaging

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04337268
• Other study ID #: H-18050603
• Status: Completed
• Phase: N/A
• Start date: April 1, 2019
• Est. completion date: March 1, 2020

Study information

• Verified date: April 2020
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study investigates the hypothesis, that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation.

Description:

Human studies have recently demonstrated a significant natriuretic effect of GLP-1 when the extracellular fluid volume (ECFV) is expanded by intravenous sodium-loading; in these studies, there was a suppression of ANG II with no change in net renal hemodynamics, pointing to a tubular mechanism for reduced NaCl reabsorption secondary to the ANG II suppression. In the current randomized and controlled study, investigators aim to test the hypothesis that GLP-1's suppression of ANG II and natriuretic action increase medullary perfusion and decrease oxygen consumption, leading to higher tissue oxygenation. Thus, contributing to the renoprotective action of GLP-1.

Under fixed sodium intake for 4 days before each study day, 10 healthy male participants will be investigated during a 1-hour infusion of GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Interleaved measurements of RAF, oxygenation (T2*) and perfusion by arterial spin labeling in the renal cortex and medulla at fixed time points will be conducted, using Magnetic Resonance Imaging (MRI).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 1, 2020
• Est. primary completion date: March 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 60 Years

Eligibility

Inclusion Criteria:

• Normal health demonstrated by medical examination.

• Normal values for fasting plasma glucose, total cholesterol, triglyceride, HDL, LDL, creatinine, AST, ALT and electrolyte concentrations.

Exclusion Criteria:

• Immunosuppressive treatment for the previous 12 months.

• Alcohol abuse.

• Medical treatment with oral glucocorticoids, dipeptidyl peptidase-4 (DPP-4) inhibitors, or GLP-1 receptor agonists that, in the opinion of the investigator, may interfere with glucose metabolism.

• Use of lithium.

• Medical treatment that affects insulin secretion or cardiovascular efficacy goals.

• Liver disease (ALT> 2 x normal value).

• Renal impairment (creatinine> 130 µM and / or albuminuria).

• Severe claustrophobia.

• MRI incompatible foreign bodies.

Related Conditions & MeSH terms

• The GLP-1-mediated Gut-kidney Axis

Intervention

Drug:
• Glucagon-Like Peptide 1
Intravenous infusion (1.5 pmol/kg/min) for 60 min.
• saline 0.9%
Intravenous infusion for 60 min.

Locations

Country	Name	City	State
Denmark	Rigshospitalet - Glostrup	Glostrup	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Department of Cardiovascular and Renal Research, University of Southern Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (8)

Asmar A, Asmar M, Simonsen L, Madsbad S, Holst JJ, Hartmann B, Sorensen CM, Bülow J. Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men. Physiol Rep. 2017 Feb;5(3). pii: e13073. doi: 10.14814/phy2.13073. — View Citation

Asmar A, Cramon PK, Simonsen L, Asmar M, Sorensen CM, Madsbad S, Moro C, Hartmann B, Jensen BL, Holst JJ, Bülow J. Extracellular Fluid Volume Expansion Uncovers a Natriuretic Action of GLP-1: A Functional GLP-1-Renal Axis in Man. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2509-2519. doi: 10.1210/jc.2019-00004. — View Citation

Asmar A, Simonsen L, Asmar M, Madsbad S, Holst JJ, Frandsen E, Moro C, Jonassen T, Bülow J. Renal extraction and acute effects of glucagon-like peptide-1 on central and renal hemodynamics in healthy men. Am J Physiol Endocrinol Metab. 2015 Apr 15;308(8):E641-9. doi: 10.1152/ajpendo.00429.2014. Epub 2015 Feb 10. — View Citation

Asmar A, Simonsen L, Asmar M, Madsbad S, Holst JJ, Frandsen E, Moro C, Sorensen CM, Jonassen T, Bülow J. Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy. Am J Physiol Endocrinol Metab. 2016 May 1;310(9):E744-53. doi: 10.1152/ajpendo.00518.2015. Epub 2016 Mar 8. — View Citation

Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007 Oct;87(4):1409-39. Review. — View Citation

Körner M, Stöckli M, Waser B, Reubi JC. GLP-1 receptor expression in human tumors and human normal tissues: potential for in vivo targeting. J Nucl Med. 2007 May;48(5):736-43. — View Citation

Pyke C, Heller RS, Kirk RK, Ørskov C, Reedtz-Runge S, Kaastrup P, Hvelplund A, Bardram L, Calatayud D, Knudsen LB. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology. 2014 Apr;155(4):1280-90. doi: 10.1210/en.2013-1934. Epub 2014 Jan 27. — View Citation

Skov J, Dejgaard A, Frøkiær J, Holst JJ, Jonassen T, Rittig S, Christiansen JS. Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men. J Clin Endocrinol Metab. 2013 Apr;98(4):E664-71. doi: 10.1210/jc.2012-3855. Epub 2013 Mar 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T2* signal	Changes in T2* signal in renal cortex and medulla	1 hour
Primary	Arterial Spin Labeled (ASL)	Changes in Arterial Spin Labeled (ASL) MRI Perfusion Imaging in renal cortex and medulla	1 hour
Primary	Renal Artery Flow Phase (RAF)	Changes in Renal Artery Flow Phase (RAF)-Contrast Magnetic Resonance	1 hour