The Influence of High and Low Salt on Exosomes in the Urine

Healthy Clinical Trial

Official title:

The Influence of High and Low Salt on Exosomes in the Urine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02823613
• Other study ID #: RZL-SDU-IMM-CVR
• Status: Completed
• Phase: N/A
• Start date: August 2016
• Est. completion date: May 23, 2019

Study information

• Verified date: April 2020
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The hypothesis is that changes in the epithelial sodium channel (ENaC) in the kidney is reflected in urinary exosomes and that the amount of ENaC as well as the cleavage degree is upregulated in conditions with low salt.

Description:

Methods:

Exosomes will be isolated from spot urine by ultracentrifugation and tested using western blotting. In-house developed antibodies against different parts of the ENaC gamma subunit as well as commercial antibodies will be used. A marker for exosomes will validate the presence of exosomes in the urine.

Power considerations:

In this cross over salt-intervention study with quantification of ENaC the investigators refer to a published study regarding the sodium-chloride co-transporter (NCC) in the kidney, were rats where given aldosterone infusion or a low salt diet. In this study n=6 was sufficient to detect a 2-3 fold change in NCC in urinary exosomes. Furthermore 5 patients with primary aldosteronism had a significant increase in NCC in urinary exosomes (N. Lubbe et al, Hypertension 2012).

On the basis of this the investigators choose to test 10 persons, but are not able to make a regular power calculation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 23, 2019
• Est. primary completion date: May 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy men aged 20-40

• Body Mass Index (BMI, weight/height^2) between 18 and 25.

Exclusion Criteria:

• Increased blood pressure (hypertension) or in treatment for high blood pressure

• Diabetes

• Regular medical intake

• Smoking

• Expectation of lacking cooperation or lack of understanding of the experiment

• Clinical relevant organic or systemic disease including malign disease

• Decreased kidney function

Related Conditions & MeSH terms

• Healthy

Intervention

Dietary Supplement:
• High salt diet followed by low salt diet
High salt diet (250 mmol/day) in 5 days followed by low salt diet (60-70 mmol/day) in 5 days.
• Low salt diet followed by high salt diet
Low salt diet (60-70 mmol/day) in 5 days followed by high salt diet (250 mmol/day) in 5 days.

Locations

Country	Name	City	State
Denmark	University of Southern Denmark	Odense

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern Denmark	Beckett Foundation, Danish Diabetes Academy, Odense University Hospital

Country where clinical trial is conducted

Denmark, 

References & Publications (2)

van der Lubbe N, Jansen PM, Salih M, Fenton RA, van den Meiracker AH, Danser AH, Zietse R, Hoorn EJ. The phosphorylated sodium chloride cotransporter in urinary exosomes is superior to prostasin as a marker for aldosteronism. Hypertension. 2012 Sep;60(3):741-8. doi: 10.1161/HYPERTENSIONAHA.112.198135. Epub 2012 Jul 30. — View Citation

Zachar RM, Skjødt K, Marcussen N, Walter S, Toft A, Nielsen MR, Jensen BL, Svenningsen P. The epithelial sodium channel ?-subunit is processed proteolytically in human kidney. J Am Soc Nephrol. 2015 Jan;26(1):95-106. doi: 10.1681/ASN.2013111173. Epub 2014 Jul 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in epithelial sodium channel (ENaC) appearance in urinary exosomes	Semiquantitative western blotting	After 5 days on high or low salt diet
Secondary	Plasma aldosterone	Concentration in plasma.	Before study start and after 5 days on high or low salt diet
Secondary	Renin	Concentration in plasma.	Before study start and after 5 days on high or low salt diet