HaemoDYNAMICs in Primary and Secondary Hypertension

NCT ID: NCT01742702

Last Updated: 2021-08-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2006-05-25

Study Completion Date

2025-12-31

Brief Summary

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The primary aim of the present study was to examine the haemodynamic changes in primary hypertension and secondary hypertension (renal diseases, endocrine diseases, obesity-associated hypertension) with a non-invasive haemodynamic measurement protocol utilizing radial pulse wave analysis and whole-body impedance cardiography in both supine position and during head-up tilt. For comparison, haemodynamics of subjects with chronic fatigue syndrome will also be recorded.

Detailed Description

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Elevated blood pressure (BP) and related cardiovascular complications are the leading causes of morbidity and mortality in the modern world. In routine clinical practice, the haemodynamic status is commonly assessed by measuring heart rate and blood pressure at rest, which provides only limited information about functional haemodynamic status. In addition, the haemodynamic changes resulting in similar elevations of BP may differ substantially between patients and disorders.

Therefore, we investigated the haemodynamic changes in primary and secondary hypertension and in the control subjects with non-invasive radial pulse wave analysis and whole-body impedance cardiography. The method includes the determination of volume status using bioimpedance spectroscopy, determination of peripheral and central BP, cardiac function, vascular resistance, arterial compliance and indices of pulse wave reflection. Besides the measurements performed in the supine position, passive orthostatic challenge is included in the protocol to assess the upright functional haemodynamic status.

The repeatability and reproducibility of the protocol was first examined with a double-blind, randomized protocol in 35 subjects (methodological study group), and after that the administration of research drugs has been open-label. The effects of single doses of two largely endothelium-dependent agents, inhaled salbutamol and intravenous L-arginine, and one endothelium-independent agent, sublingual nitroglycerin, were investigated. However, challenges with the acute dosing of all medical compounds was terminated at the end of December 2016. Thereafter, the measurement protocol has included supine and upright recordings on the tilt-table, followed by supine measurements during paced breathing (15 breaths per minute for 5 minutes, 6 breaths per minute for 5 minutes) that modulate the autonomic nervous tone.

The study population has consisted of subgroups described below. The study protocol of each subgroup has been approved by the ethics committee of the Pirkanmaa Hospital District (Ethics committee ID's above), and the administration of research drugs has also been approved by the Finnish Agency for Medicines (EudraCT-numbers above).

Conditions

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Primary Hypertension Secondary Hypertension Aortic Stenosis Renal Insufficiency

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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DYNAMIC (ongoing)

Subjects with primary or secondary hypertension and normotensive control subjects. In addition haemodynamic recordings to 50 subjects suffering from chronic fatigue syndrome will be performed.

No interventions assigned to this group

AERO-DYNAMIC (recordings completed)

Subjects who had voluntarily decided to participate in a professionally coached marathon school (Varala Sports Institute, Tampere) were given the chance for haemodynamic recordings before, during and after the training protocol.

Nitroglycerin 0.25 mg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a single dose of sublingual nitroglycerin was given to examine the associated acute haemodynamic effects (recordings completed).

Salbutamol 400 µg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a 400 µg dose of inhaled salbutamol was given to examine the associated acute haemodynamic effects (recordings completed).

Liquorice (recordings completed)

Normotensive subjects, daily liquorice ingestion (daily glycyrrhizin dose 290-370 mg) for 2 weeks, haemodynamic measurements before and after the intervention.

Nitroglycerin 0.25 mg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a single dose of sublingual nitroglycerin was given to examine the associated acute haemodynamic effects (recordings completed).

Salbutamol 400 µg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a 400 µg dose of inhaled salbutamol was given to examine the associated acute haemodynamic effects (recordings completed).

Liquorice (2 weeks, glycyrrhizin 290-370 mg daily, no longer given since 2012)

Intervention Type DIETARY_SUPPLEMENT

Daily liquorice intake (daily glycyrrhizin dose 290-370 mg) for two weeks, measurements before and after intervention (recordings completed).

Milk polypeptides (recordings completed)

Daily ingestion of yoghurt containing small milk casein-derived polypeptides for 12 weeks versus placebo yoghurt.

Small milk casein-derived polypeptides (12 weeks daily, recordings completed 2011)

Intervention Type DIETARY_SUPPLEMENT

Daily intake of yoghurt containing small milk casein-derived polypeptides (12 weeks) and placebo yoghurt (12 weeks), measurements before and after intervention (recordings completed 2011).

Bisoprolol (recordings completed)

Hypertensive subjects, bisoprolol 5 mg once daily versus placebo in a double-blind, cross-over protocol.

Nitroglycerin 0.25 mg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a single dose of sublingual nitroglycerin was given to examine the associated acute haemodynamic effects (recordings completed).

Salbutamol 400 µg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a 400 µg dose of inhaled salbutamol was given to examine the associated acute haemodynamic effects (recordings completed).

Bisoprolol (5 mg daily for 3 weeks, recordings completed 2011)

Intervention Type DRUG

Bisoprolol 5 mg daily for 3 weeks and placebo tablet daily for 3 weeks, double-blind, randomized, placebo-controlled cross-over protocol. Measurements before and after interventions (recordings completed 2011).

Aortic stenosis (ongoing)

Subjects with aortic stenosis confirmed by echocardiography

No interventions assigned to this group

Methodological (recordings completed)

35 normotensive subjects who received research drugs (nitroglycerin, salbutamol, placebo resoriblet, placebo inhalation, L-arginine infusion, saline infusion) in a placebo-controlled, double-blinded manner

Nitroglycerin 0.25 mg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a single dose of sublingual nitroglycerin was given to examine the associated acute haemodynamic effects (recordings completed).

Salbutamol 400 µg (single dose, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 a 400 µg dose of inhaled salbutamol was given to examine the associated acute haemodynamic effects (recordings completed).

L-arginine (10 min infusion, no longer given since January 2017)

Intervention Type DRUG

From the beginning of the study until the end of year 2016 L-arginine infusion 10 mg/kg/min could be given for 10 minutes to examine acute haemodynamic effects (recordings completed).

Participants of Ironman Triathlon

Altogether 80 athletes participating in a full length Ironman competition. Non-invasive recordingds are performed under normal conditions during the training period and after completion of a full-length Ironman competition.

No interventions assigned to this group

Interventions

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Nitroglycerin 0.25 mg (single dose, no longer given since January 2017)

From the beginning of the study until the end of year 2016 a single dose of sublingual nitroglycerin was given to examine the associated acute haemodynamic effects (recordings completed).

Intervention Type DRUG

Salbutamol 400 µg (single dose, no longer given since January 2017)

From the beginning of the study until the end of year 2016 a 400 µg dose of inhaled salbutamol was given to examine the associated acute haemodynamic effects (recordings completed).

Intervention Type DRUG

L-arginine (10 min infusion, no longer given since January 2017)

From the beginning of the study until the end of year 2016 L-arginine infusion 10 mg/kg/min could be given for 10 minutes to examine acute haemodynamic effects (recordings completed).

Intervention Type DRUG

Liquorice (2 weeks, glycyrrhizin 290-370 mg daily, no longer given since 2012)

Daily liquorice intake (daily glycyrrhizin dose 290-370 mg) for two weeks, measurements before and after intervention (recordings completed).

Intervention Type DIETARY_SUPPLEMENT

Small milk casein-derived polypeptides (12 weeks daily, recordings completed 2011)

Daily intake of yoghurt containing small milk casein-derived polypeptides (12 weeks) and placebo yoghurt (12 weeks), measurements before and after intervention (recordings completed 2011).

Intervention Type DIETARY_SUPPLEMENT

Bisoprolol (5 mg daily for 3 weeks, recordings completed 2011)

Bisoprolol 5 mg daily for 3 weeks and placebo tablet daily for 3 weeks, double-blind, randomized, placebo-controlled cross-over protocol. Measurements before and after interventions (recordings completed 2011).

Intervention Type DRUG

Other Intervention Names

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Nitro resoriblet, Orion Pharma, Espoo, Finland Ventoline, GlaxoSmithKline, Uxbridge, Middlesex, UK L-arginine HCl 20 mg ml/l, B. Braun Ag, Melsungen, Germany Halva liquorice (TM), Kouvola liquorice (TM) Valio (TM) evolus yoghurt Emconcor 5 mg, Merck KGaA, Darmstadt, Germany

Eligibility Criteria

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Inclusion Criteria

* Independent, community-dwelling adults
* Hypertensive subjects (primary or secondary hypertension)
* Normotensive control subjects
* Subjects with aortic stenosis (subgroup "aortic stenosis")
* Participants of Ironman Triathlon competition

Exclusion Criteria

* Pregnancy
* Systolic blood pressure \<90 mmHg
* Allergies to test compounds
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Finnish Foundation for Cardiovascular Research

OTHER

Sponsor Role collaborator

Paavo Nurmi Foundation

UNKNOWN

Sponsor Role collaborator

Sigrid Jusélius Foundation

OTHER

Sponsor Role collaborator

Finnish Cultural Foundation

OTHER

Sponsor Role collaborator

Tampere Tuberculosis Foundation

OTHER

Sponsor Role collaborator

Medical Research Fund of the Tampere University Hospital, Finland

OTHER

Sponsor Role collaborator

Aarne Koskelo Foundation

OTHER

Sponsor Role collaborator

Finnish Medical Foundation

NETWORK

Sponsor Role collaborator

Finnish Kidney Foundation

UNKNOWN

Sponsor Role collaborator

Päivikki and Sakari Sohlberg Foundation, Finland

OTHER

Sponsor Role collaborator

Tampere University

OTHER

Sponsor Role lead

Responsible Party

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Ilkka Pörsti, MD

MD, PhD, Professor of Internal Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ilkka Pörsti, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Tampere University

Locations

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Tampere University

Tampere, Southern Finland, Finland

Site Status RECRUITING

Tampere University Hospital

Tampere, Southern Finland, Finland

Site Status RECRUITING

Countries

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Finland

Facility Contacts

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Ilkka H Pörsti, MD, PhD, Professor

Role: primary

+358 40 5486507

Elina J Hautaniemi, PhD

Role: backup

Ilkka H Pörsti, Professor

Role: primary

Elina J Hautaniemi, PhD

Role: backup

References

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Taurio J, Hautaniemi EJ, Koskela JK, Eraranta A, Hamalainen M, Tikkakoski A, Kettunen JA, Kahonen M, Niemela O, Moilanen E, Mustonen J, Porsti I. The characteristics of elevated blood pressure in abdominal obesity correspond to primary hypertension: a cross-sectional study. BMC Cardiovasc Disord. 2023 Mar 27;23(1):161. doi: 10.1186/s12872-023-03150-w.

Reference Type DERIVED
PMID: 36973671 (View on PubMed)

Koskela JK, Tahvanainen A, Tikkakoski AJ, Kangas P, Uitto M, Viik J, Kahonen M, Mustonen J, Porsti I. Resting heart rate predicts cardiac autonomic modulation during passive head-up tilt in subjects without cardiovascular diseases. Scand Cardiovasc J. 2022 Dec;56(1):138-147. doi: 10.1080/14017431.2022.2079713.

Reference Type DERIVED
PMID: 35652524 (View on PubMed)

Hamid H, Kurra V, Choudhary MK, Bouquin H, Niemela O, Kahonen MAP, Mustonen JT, Porsti IH, Koskela JK. Plasma uric acid is related to large arterial stiffness but not to other hemodynamic variables: a study in 606 normotensive and never-medicated hypertensive subjects. BMC Cardiovasc Disord. 2021 May 26;21(1):257. doi: 10.1186/s12872-021-02072-9.

Reference Type DERIVED
PMID: 34039285 (View on PubMed)

Kokko E, Nevalainen PI, Choudhary MK, Koskela J, Tikkakoski A, Huhtala H, Niemela O, Viukari M, Mustonen J, Matikainen N, Porsti I. Aldosterone-to-renin ratio is related to arterial stiffness when the screening criteria of primary aldosteronism are not met. Sci Rep. 2020 Nov 13;10(1):19804. doi: 10.1038/s41598-020-76718-7.

Reference Type DERIVED
PMID: 33188272 (View on PubMed)

Hautaniemi EJ, Tikkakoski AJ, Eraranta A, Kahonen M, Hamalainen E, Turpeinen U, Huhtala H, Mustonen J, Porsti IH. Liquorice ingestion attenuates vasodilatation via exogenous nitric oxide donor but not via beta2-adrenoceptor stimulation. PLoS One. 2019 Oct 18;14(10):e0223654. doi: 10.1371/journal.pone.0223654. eCollection 2019.

Reference Type DERIVED
PMID: 31626649 (View on PubMed)

Kangas P, Tahvanainen A, Tikkakoski A, Koskela J, Uitto M, Viik J, Kahonen M, Koobi T, Mustonen J, Porsti I. Increased Cardiac Workload in the Upright Posture in Men: Noninvasive Hemodynamics in Men Versus Women. J Am Heart Assoc. 2016 Jun 21;5(6):e002883. doi: 10.1161/JAHA.115.002883.

Reference Type DERIVED
PMID: 27329447 (View on PubMed)

Wilenius M, Tikkakoski AJ, Tahvanainen AM, Haring A, Koskela J, Huhtala H, Kahonen M, Koobi T, Mustonen JT, Porsti IH. Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication. BMC Cardiovasc Disord. 2016 Jun 7;16:131. doi: 10.1186/s12872-016-0303-6.

Reference Type DERIVED
PMID: 27266507 (View on PubMed)

Tahvanainen AM, Tikkakoski AJ, Koskela JK, Nordhausen K, Viitala JM, Leskinen MH, Kahonen MA, Koobi T, Uitto MT, Viik J, Mustonen JT, Porsti IH. The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers. BMC Cardiovasc Disord. 2016 May 23;16:101. doi: 10.1186/s12872-016-0281-8.

Reference Type DERIVED
PMID: 27216309 (View on PubMed)

Leskinen MH, Hautaniemi EJ, Tahvanainen AM, Koskela JK, Paallysaho M, Tikkakoski AJ, Kahonen M, Koobi T, Niemela O, Mustonen J, Porsti IH. Daily liquorice consumption for two weeks increases augmentation index and central systolic and diastolic blood pressure. PLoS One. 2014 Aug 25;9(8):e105607. doi: 10.1371/journal.pone.0105607. eCollection 2014.

Reference Type DERIVED
PMID: 25153328 (View on PubMed)

Koskela JK, Tahvanainen A, Haring A, Tikkakoski AJ, Ilveskoski E, Viitala J, Leskinen MH, Lehtimaki T, Kahonen MA, Koobi T, Niemela O, Mustonen JT, Porsti IH. Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects. BMC Cardiovasc Disord. 2013 Nov 15;13:102. doi: 10.1186/1471-2261-13-102.

Reference Type DERIVED
PMID: 24237764 (View on PubMed)

Other Identifiers

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2006-002065-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2009-014542-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

R07110M

Identifier Type: OTHER

Identifier Source: secondary_id

R07053M

Identifier Type: OTHER

Identifier Source: secondary_id

R08012

Identifier Type: OTHER

Identifier Source: secondary_id

R09103M

Identifier Type: OTHER

Identifier Source: secondary_id

R10056

Identifier Type: OTHER

Identifier Source: secondary_id

R06086M

Identifier Type: OTHER

Identifier Source: secondary_id

R21094

Identifier Type: OTHER

Identifier Source: secondary_id

R06086M

Identifier Type: -

Identifier Source: org_study_id

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