New Biomarkers and Difficult-to-treat Hypertension

NCT03034265 | Completed

• 1 other identifier: Study 3003
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the concentrations and variabilities of urinary exosomal sodium channels and plasma angiotensins in patients with difficult-to-treat arterial hypertension and to investigate their dependency on clinical parameters and sampling conditions.

Conditions

Hypertension

Keywords

hypertension; exosome; angiotensin; sodium channel; kidney; aldosterone; renin; urine

Outcome Measures

Primary Outcomes (2)

• Plasma concentration of Ang peptides

  2nd scheduled visit (5 days to 4 weeks after 1st visit)

• Urinary concentration of exosomal Na channel proteins

  2nd scheduled visit (5 days to 4 weeks after 1st visit)

Secondary Outcomes (4)

• 24h urinary Na excretion

  2nd scheduled visit (5 days to 4 weeks after 1st visit)

• Plasma renin concentration

  2nd scheduled visit (5 days to 4 weeks after 1st visit)

• Plasma aldosterone concentration

  2nd scheduled visit (5 days to 4 weeks after 1st visit)

• Repeatability of Ang peptide and urinary exosomal Na channel concentrations under spontaneous vs. standardized laboratory conditions.

  1st visit vs. 2nd scheduled visit (5 days to 4 weeks after 1st visit)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Amblatory patients with difficult-to-treat hypertension referred to the hypertension clinic for evaluation

You may qualify if:

• Patients with ≥2 antihypertensive drugs for ≥3 months
• Reported blood pressure ≥140/90 mmHg and/or patient reported as having medically uncontrolled hypertension by the referring physician
• Age ≥18 years, capacity to provide and granted written informed consent

You may not qualify if:

• Chronic stage 4-5 renal insufficiency; glomerulonephritis, liver insufficiency (Child-Pugh B or C), chronic obstructive pulmonary disease Global Initiative for Obstructive Lung Disease grade 4; chronic heart failure New York Heart Association class IV
• Known secondary hypertension
• Mandatory RAAS-blockers (e.g. converting enzyme inhibitors, angiotensin type 1 receptor blockers), beta-adrenoceptor blockers, centrally acting sympatholytics and diuretics that cannot be paused adequately before visit 2
• Mean sitting office blood pressure \>190/110 mmHg measured 3x on visit 1
• Normotension on visit 1 (mean seated office blood pressure measured 3x \<140/90 mmHg)
• Insufficient knowledge of project language and absence of an interpreter for study communications
• Pregnancy or lactation
• Scheduled clinical visit 2 outside routine workflow time-line (\<5 or \>31 days after visit 1)
• Inability to follow procedures (e.g. relevant psychiatric disorder or dementia)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Zurich: collaborator

Study Sites (1)

Department of Nephrology and Hypertension, Inselspital, Bern University Hospital

Bern, 3010, Switzerland

Location

Related Publications (8)

• Campbell DJ, Nussberger J, Stowasser M, Danser AH, Morganti A, Frandsen E, Menard J. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem. 2009 May;55(5):867-77. doi: 10.1373/clinchem.2008.118000. Epub 2009 Mar 5.

  PMID: 19264850 BACKGROUND

• Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 2011 Aug 30;124(9):1046-58. doi: 10.1161/CIRCULATIONAHA.111.030189. Epub 2011 Aug 8.

  PMID: 21824920 BACKGROUND

• Glicklich D, Frishman WH. Drug therapy of apparent treatment-resistant hypertension: focus on mineralocorticoid receptor antagonists. Drugs. 2015 Apr;75(5):473-85. doi: 10.1007/s40265-015-0372-3.

  PMID: 25787734 BACKGROUND

• Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013 Jul;31(7):1281-357. doi: 10.1097/01.hjh.0000431740.32696.cc. No abstract available.

  PMID: 23817082 BACKGROUND

• Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73. doi: 10.1073/pnas.0403453101. Epub 2004 Aug 23.

  PMID: 15326289 BACKGROUND

• Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH. Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res. 2015 Mar 13;116(6):960-75. doi: 10.1161/CIRCRESAHA.116.303587.

  PMID: 25767283 BACKGROUND

• 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.

  PMID: 22851731 BACKGROUND

• Wolley MJ, Stowasser M. Resistant Hypertension and Chronic Kidney Disease: a Dangerous Liaison. Curr Hypertens Rep. 2016 Apr;18(5):36. doi: 10.1007/s11906-016-0641-x.

  PMID: 27072829 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood, urine

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jürgen Bohlender, M.D.

  Inselspital, Bern University Hospital, Freiburgstr. 4, 3010 Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2017
• First Posted: January 27, 2017
• Study Start: May 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: December 20, 2017

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will share

Locations

CH (1)