NCT02380157

Brief Summary

Project titel: Oral potassium supplementation in healthy men - interactions with the renin-angiotensin-aldosterone system and the sympathetic nervous system Protocol number: KARAASS-1 EudraCT number: 2013-004460-66 Introduction The global burden of hypertension is huge. This project focuses on the role of potassium in human blood pressure regulation. A potassium rich diet lowers blood pressure and some studies have shown an increase in blood pressure during potassium depletion. Thus an inverse correlation between potassium intake and blood pressure exists. In this trial the objective is to test how an oral potassium supplementation, administered in form of the drug Kaleorid®, interacts with the renin-angiotensin-aldosterone system and the sympathetic nervous system. Methods This is a randomized clinical placebo-controlled double-blinded crossover trial. A group of healthy men will be randomized to either 4 weeks treatment with the drug Kaleorid®, 750mg, 3 tablets 3 times daily or to 4 weeks treatment with placebo. On day 26 in the first treatment period the participants meet at the hospital to start a 24-hours ambulatory blood pressure and collect a 48-hours urine sample. The same day a blood sample, an electrocardiogram (ECG) and a fat biopsy from the gluteal region will be done. The fat biopsy is expected to contain resistance vessels, which are to be investigated further in the laboratory. On day 28 in the first treatment period the participants meet at the hospital again and are tested with an intravenous Angiotensin II infusion followed by continuous measurement of blood pressure and the following aldosterone response (using blood samples). Blood pressure will be measured with Finger Plethysmography and vascular tonus will be evaluated with the use of Impedance Cardiography, Finger Plethysmography and Doppler Ultrasound measurements of blood flow before, during and after the Angiotensin II infusion. After this first period of treatment and testing a "washout" period of two weeks is inserted. After "washout", the participants crossover and starts the second treatment period. Feasibility All necessary authorities have approved the trial and all cooperation is established.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Mar 2015

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 17, 2015

Completed
12 days until next milestone

Study Start

First participant enrolled

March 1, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 5, 2015

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

January 6, 2017

Status Verified

January 1, 2017

Enrollment Period

1.8 years

First QC Date

February 17, 2015

Last Update Submit

January 5, 2017

Conditions

Blood PressureHypertension

Keywords

Blood pressurePotassium, DietaryRenin-angiotensin-aldosterone systemSympathetic nervous system

Outcome Measures

Primary Outcomes (1)

  • Change in Angiotensin II stimulated S-aldosterone

    Day 28 in each treatment period up to 70 days from start in the study

Secondary Outcomes (11)

  • Change in Angiotensin II stimulated blood pressure

    Day 28 in each treatment period up to 70 days from start in the study

  • Change in Angiotensin II stimulated total peripheral resistance (TPR)

    Day 28 in each treatment period up to 70 days from start in the study

  • Change in Angiotensin II stimulated resistance index (RI) in central vessels of the abdomen

    Day 28 in each treatment period up to 70 days from start in the study

  • Level of receptor expression in resistance vessels from fat biopsies

    Day 26 in each treatment period up to 70 days from start in the study

  • Level of receptor function in resistance vessels from fat biopsies

    Day 26 in each treatment period up to 70 days from start in the study

  • +6 more secondary outcomes

Study Arms (2)

Kaleorid

EXPERIMENTAL

4 weeks treatment with Kaleorid, 750mg, 3 tablets 3 times daily.

Drug: Kaleorid, 750mg (trade name), Potassium chloride (active substance)

Placebo

PLACEBO COMPARATOR

4 weeks treatment with Placebo tablets, 3 tablets 3 times daily.

Drug: Placebo

Interventions

Kaleorid, 750mg (trade name), Potassium chloride (active substance)DRUG

4 weeks treatment with Kaleorid, 750mg, 3 tablets 3 times daily.

Kaleorid
PlaceboDRUG

4 weeks treatment with Placebo tablets, 3 tablets 3 times daily.

Placebo

Eligibility Criteria

Age20 Years - 55 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Male
  • Age: 20-55
  • Office Blood Pressure: \< 140/90 mmHg
  • BMI: 18,5-30,0 kg/m2
  • Signed consent form

You may not qualify if:

  • Diabetes mellitus
  • Cerebrovascular disease, ischemic heart disease, peripheral artery disease
  • Kidney disease
  • Adrenal disease
  • Ulcers
  • Medical treatment
  • Drug or alcohol abuse
  • Pathological ECG
  • Mental not suitable
  • Hyperkalemia

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University of Copenhagen

Glostrup, Copenhagen, Glostrup, DK-2600, Denmark

Location

Related Publications (19)

  • Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: analysis of worldwide data. Lancet. 2005 Jan 15-21;365(9455):217-23. doi: 10.1016/S0140-6736(05)17741-1.

    PMID: 15652604BACKGROUND

  • Ibsen H, Jorgensen T, Jensen GB, Jacobsen IA. [Hypertension--prevalence and treatment]. Ugeskr Laeger. 2009 Jun 8;171(24):1998-2000. Danish.

    PMID: 19523360BACKGROUND

  • He J, Whelton PK. Epidemiology and prevention of hypertension. Med Clin North Am. 1997 Sep;81(5):1077-97. doi: 10.1016/s0025-7125(05)70568-x.

    PMID: 9308599BACKGROUND

  • Whelton PK. Epidemiology of hypertension. Lancet. 1994 Jul 9;344(8915):101-6. doi: 10.1016/s0140-6736(94)91285-8.

    PMID: 7912348BACKGROUND

  • Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997 Apr 17;336(16):1117-24. doi: 10.1056/NEJM199704173361601.

    PMID: 9099655BACKGROUND

  • Whelton PK, He J, Cutler JA, Brancati FL, Appel LJ, Follmann D, Klag MJ. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA. 1997 May 28;277(20):1624-32. doi: 10.1001/jama.1997.03540440058033.

    PMID: 9168293BACKGROUND

  • Larsson SC, Orsini N, Wolk A. Dietary potassium intake and risk of stroke: a dose-response meta-analysis of prospective studies. Stroke. 2011 Oct;42(10):2746-50. doi: 10.1161/STROKEAHA.111.622142. Epub 2011 Jul 28.

    PMID: 21799170BACKGROUND

  • Siani A, Strazzullo P, Giacco A, Pacioni D, Celentano E, Mancini M. Increasing the dietary potassium intake reduces the need for antihypertensive medication. Ann Intern Med. 1991 Nov 15;115(10):753-9. doi: 10.7326/0003-4819-115-10-753.

    PMID: 1929022BACKGROUND

  • Krishna GG, Miller E, Kapoor S. Increased blood pressure during potassium depletion in normotensive men. N Engl J Med. 1989 May 4;320(18):1177-82. doi: 10.1056/NEJM198905043201804.

    PMID: 2624617BACKGROUND

  • Krishna GG, Kapoor SC. Potassium depletion exacerbates essential hypertension. Ann Intern Med. 1991 Jul 15;115(2):77-83. doi: 10.7326/0003-4819-115-2-77.

    PMID: 2058867BACKGROUND

  • Adrogue HJ, Madias NE. Sodium and potassium in the pathogenesis of hypertension. N Engl J Med. 2007 May 10;356(19):1966-78. doi: 10.1056/NEJMra064486. No abstract available.

    PMID: 17494929BACKGROUND

  • Matthesen SK, Larsen T, Vase H, Lauridsen TG, Pedersen EB. Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans. Scand J Clin Lab Invest. 2012 Feb;72(1):78-86. doi: 10.3109/00365513.2011.635216. Epub 2011 Dec 12.

    PMID: 22149452BACKGROUND

  • Rainey WE, Bird IM, Mason JI. The NCI-H295 cell line: a pluripotent model for human adrenocortical studies. Mol Cell Endocrinol. 1994 Apr;100(1-2):45-50. doi: 10.1016/0303-7207(94)90277-1.

    PMID: 8056157BACKGROUND

  • Rainey WE, Saner K, Schimmer BP. Adrenocortical cell lines. Mol Cell Endocrinol. 2004 Dec 30;228(1-2):23-38. doi: 10.1016/j.mce.2003.12.020.

    PMID: 15541570BACKGROUND

  • 15. Egfjord M, Dreier R, Ravn L, Hofman-Bang J. Extracellular potassium modulated aldosterone secretion in relation to hypertensive states. 2013. Submitted.

    BACKGROUND

  • Bentley-Lewis R, Adler GK, Perlstein T, Seely EW, Hopkins PN, Williams GH, Garg R. Body mass index predicts aldosterone production in normotensive adults on a high-salt diet. J Clin Endocrinol Metab. 2007 Nov;92(11):4472-5. doi: 10.1210/jc.2007-1088. Epub 2007 Aug 28.

    PMID: 17726083BACKGROUND

  • Cargill RI, Coutie WJ, Lipworth BJ. The effects of angiotensin II on circulating levels of natriuretic peptides. Br J Clin Pharmacol. 1994 Aug;38(2):139-42. doi: 10.1111/j.1365-2125.1994.tb04337.x.

    PMID: 7981014BACKGROUND

  • Seidelin PH, McMurray JJ, Brown RA, Struthers AD. The effect of angiotensin II and noradrenaline alone and in combination on renal sodium excretion in man. Br J Clin Pharmacol. 1989 Jun;27(6):803-9. doi: 10.1111/j.1365-2125.1989.tb03443.x.

    PMID: 2757896BACKGROUND

  • Dreier R, Andersen UB, Forman JL, Sheykhzade M, Egfjord M, Jeppesen JL. Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study. J Am Heart Assoc. 2021 May 4;10(9):e018716. doi: 10.1161/JAHA.120.018716. Epub 2021 Apr 19.

    PMID: 33870711DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

Potassium Chloride

Condition Hierarchy (Ancestors)

Vascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

ChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsPotassium Compounds

Study Officials

  • Rasmus Dreier, M.D.

    Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University of Copenhagen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Doctor

Study Record Dates

First Submitted

February 17, 2015

First Posted

March 5, 2015

Study Start

March 1, 2015

Primary Completion

December 1, 2016

Study Completion

December 1, 2016

Last Updated

January 6, 2017

Record last verified: 2017-01

Locations

DK(1)