HaemoDYNAMICs in Primary and Secondary Hypertension

Aortic Stenosis Clinical Trial

— DYNAMIC  

Official title:

Non-Invasive HaemoDYNAMICs in Primary and Secondary Hypertension: the DYNAMIC-study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01742702
• Other study ID #: R06086M
• Secondary ID: 2006-002065-3920
• Status: Recruiting
• Start date: May 25, 2006
• Est. completion date: December 31, 2025

Study information

• Verified date: August 2021
• Source: Tampere University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Aortic Stenosis
• Aortic Valve Stenosis
• Essential Hypertension
• Hypertension
• Neoplasm Metastasis
• Primary Hypertension
• Renal Insufficiency
• Secondary Hypertension

Intervention

Drug:
• 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).
• 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).
• 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).

Dietary Supplement:
• 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).
• 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).

Drug:
• 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).

Locations

Country	Name	City	State
Finland	Tampere University	Tampere	Southern Finland
Finland	Tampere University Hospital	Tampere	Southern Finland

Sponsors (11)

Lead Sponsor	Collaborator
Tampere University	Aarne Koskelo Foundation, Finnish Cultural Foundation, Finnish Foundation for Cardiovascular Research, Finnish Kidney Foundation, Finnish Medical Foundation, Medical Research Fund of the Tampere University Hospital, Finland, Paavo Nurmi Foundation, Päivikki and Sakari Sohlberg Foundation, Finland, Sigrid Jusélius Foundation, Tampere Tuberculosis Foundation

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in haemodynamic variables during the follow-up	Haemodynamic measurements are performed at baseline, and after approximately 10 years of follow-up	baseline, ten years
Primary	Cardiovascular events	All cardiovascular events during follow-up	ten years of follow-up
Secondary	Haemodynamic response to head-up tilt and research drugs	Rapid haemodynamic responses are assessed during the same measurement session (the response to head-up tilt and to research drugs salbutamol, nitroglycerin and L-arginine)	0, 5, 10, 15, 20, 25 and 30 minutes
Secondary	Haemodynamic response to bisoprolol or dietary supplements (liquorice, milk casein-derived polypeptides)	The change in haemodynamic variables after daily consumption of liquorice (2 weeks); bisoprolol (3 weeks); small milk casein-derived polypeptides (12 weeks)	baseline and after 2 weeks (liquorice); 3 weeks (bisoprolol), or 12 weeks (polypeptides)
Secondary	Haemodynamic changes induced by Ironman competition	Recordings are performed during normal conditions (training peroid) and after completion of a full-length Ironman competition	Recordings within 2 hours after completion Ironman competition, 12-18 hours later, and within 1-4 before or 4-8 weeks after the competition