Condition category
Circulatory System
Date applied
17/06/2019
Date assigned
18/06/2019
Last edited
30/04/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results

Plain English Summary

Background and study aims
Essential hypertension (high blood pressure) is associated with poor heart and blood vessel function, and an increase in nerve activity. It is thought that in this condition the muscle which constricts blood vessels is abnormally sensitive and contributes to high blood pressure. The current study is investigating the effect of time-efficient exercise training on the muscle activity of blood vessels in the legs and their control by locally released chemical messengers.

Who can participate?
Men aged 45 - 70 years, who do less than two hours of exercise each week.

What does the study involve?
We aimed at investigating the effect of 6 weeks of high-intensity exercise training (the 10-20-30 training principle) on leg vascular function (status of the blood vessels of the legs) in hypertensive males (high blood pressure) in comparison to matched normotensive males.

What are the possible benefits and risks of participating?
The benefits from participation is a thorough physical examination with ECG, broad blood sample screening, DXA-scan and fitness test. Furthermore subjects receive an effective and supervised training intervention with the aim at improving maximum oxygen uptake and lower blood pressure. The risks are small as all procedures have been running at the department for up to 25 years with very few minor complications such as skin numbness after muscle biopsies which is expected to be regained within 12 weeks, subcutaneous bleeding which leaves a haematoma that can be sore to pressure for up to 5 days, and headaches in some hypertensive individuals when dosing out of anti-hypertensive medication prior to experimental days. Risk for placing catheters in the femoral artery and vein, of the size that is used at the department, are not reported to have common side effects.

Where is the study run from?
University of Copenhagen, Dept. of Nutrition, Exercise and Sports, Denmark

When is the study starting and how long is it expected to run for?
March 2016 to December 2018

Who is funding the study?
1. Aase and Ejnar Danielsens Fund (Aase og Ejnar Danielsens Fond)
2. The Danish Ministry of Culture (Kulturministeriet)

Who is the main contact?
Dr Thomas Gunnarsson
tgunnarsson@nexs.ku.dk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Thomas Gunnarsson

ORCID ID

http://orcid.org/0000-0001-7414-3045

Contact details

Universitetsparken 13
2nd floor
Copenhagen
2100
Denmark
+4535321940
tgunnarsson@nexs.ku.dk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

Essential hypertension is associated with reduced endothelium-independent vasodilation in the lower extremity that is reversed by exercise training

Acronym

EssHypExTr

Study hypothesis

Exercise training improves blood vessel function which is related to a better blood pressure regulation in individuals with essential hypertension

Ethics approval

Approved 01/03/2015, Ethics Committee of Copenhagen and Frederiksberg communities (: De Videnskabsetiske Komiteer, Regionsgården Kongens Vænge 2, 3400 Hillerød, Denmark; +45 3866 6395; VEK@regionh.dk), ref: H-4-2014-100

Study design

Longitudinal training intervention study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Treatment

Patient information sheet

No participant information sheet available

Condition

Hypertension

Intervention

Both groups (hypertensive and normotensive individuals) trained in high-intensity exercise training 3x/week for 6 weeks. Groups were matched by age and no other diseases than high blood pressure was allowed.

Subjects performed exercise training adhering to the 10-20-30 training concept. Exercise training was conducted on cycle ergometers for 2x20 minutes in the first two weeks and 3x28 minutes the following 4 weeks. In short, 10-20-30 training consists of five consecutive 1 min intervals divided into 30, 20, and 10s at an intensity corresponding to ~30%, ~50% and ~100% of maximal intensity, respectively. For the first two weeks of training, subjects completed a 6 min low-intensity warm-up followed by two 5 min bouts interspersed by 3 min of recovery. From week 3, training volume was increased to three 5-min bouts per training session interspersed by 3 min of recovery. Likewise, weekly training sessions were increased from 2 (week 1-2) to 3 (week 3-6). Subjects were instructed to push maximally during the 10-s sprints. The total amount of training planned for each subject was 16 training sessions over the 6-week training intervention comprising forty-four consecutive 5-min bouts or 220 10-second all-out sprints. The participants in HYP and NORM completed 97±5 and 98±4 % of 16 training sessions planned, respectively, during the 6-week intervention period.

Intervention type

Behavioural

Phase

Drug names

Primary outcome measure

1. Vascular function, evaluated during infusion of acetylcholine (Miochol-E, Bausch & Lomb Inc., Bridgewater, NJ) at an infusion rate of 10, 25, and 100 µg/min/kg leg mass; sodium nitroprusside (Nitropress, Hospira Inc., Lake Forest, IL) at an infusion rate of 3, 6, and 9 µg/min/kg leg mass; and phenylephrine (Herlev apotek, Copenhagen, Denmark) at an infusion rate at 3 µg/min/kg leg mass), measured before and after the training intervention
2. Leg blood flow, ultrasound Doppler (Logic E9, GE Healthcare), measured before and after the training intervention
3. Intra-arterial and -venous blood pressure, pressure transducers (Pressure Monitoring Kit, Baxter Deerfield, IL, USA) positioned at the level of the heart, measured before and after the training intervention. Leg vascular conductance, calculated as femoral arterial blood flow divided by the difference between the mean femoral arterial and venous blood pressure, measured before and after the training intervention
4. Muscle sympathetic nervous activity (MSNA; burst frequency and incidence), microneurography i.e. direct recordings of multiunit efferent postganglionic muscle sympathetic nerve activity by use of tungsten microelectrodes with a diameter of 5µm, measured before and after the training intervention
5. 24-h ambulatory blood pressure, 24-h home measurements (TM-2430 PC2, Boso, Jungingen, Germany), measured at week -2 (screening), measured before and after the training intervention.

Secondary outcome measures

Before and after the six-week intervention period:
1. Body composition measured by multiple DXA scans
2. Maximum oxygen uptake measured by a GXT with online measurements of oxygen uptake (OxyCon pro, ViaSys, Healtcare)
3. Muscle protein content of endothalial NOS (eNOS) measured by the method of Westernblotting from vastus lateralis muscle biopsies.
4. Leg 6-keto PGF1α release (prostacyclin analogue) in arterial and venous blood samples taken before and during infusion of acetylcholine at 10 and 100 µg/min/kg leg mass, respectively
5. Plasma norepinephrine levels as a surrogate marker of sympathetic activity from arterial and venous blood samples obtained before and during infusions of acetylcholine (10 and 100 µg/min/kg leg mass), sodium nitroprusside (3 and 9 µg/min/kg leg mass )and phenylephrine (3 µg/min/kg leg mass), respectively

Overall trial start date

01/01/2016

Overall trial end date

30/11/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Age 45-70 years
2. BMI 20-35 kg∙m-2
3. Ambulatory systolic/diastolic blood pressure >140/90 (hypertensive) or <140/90 (normotensive)
4. <2 h of physical activity per week
5. HbA1c <6.5% and <48 mM

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

20

Total final enrolment

18

Participant exclusion criteria

1. Irregular resting ECG
2. History of cardiac symptoms during exercise
3. Chronic diseases other than essential hypertension
4. Use of medication other than anti-hypertensive drugs
5. Inability to perform physical exercise

Recruitment start date

01/03/2016

Recruitment end date

01/12/2018

Locations

Countries of recruitment

Denmark

Trial participating centre

University of Copenhagen, Dept. of Nutrition, Exercise and Sports
Universitetsparken 13
Copenhagen
2100
Denmark

Sponsor information

Organisation

Univeristy of Copenhagen

Sponsor details

Universitetsparken 13
Copenhagen
2100
Denmark
+4535320829
nexs@nexs.ku.dk

Sponsor type

University/education

Website

https://nexs.ku.dk

Funders

Funder type

Charity

Funder name

Aase og Ejnar Danielsens Fond

Alternative name(s)

Aase and Ejnar Danielsen Foundation

Funding Body Type

unknown

Funding Body Subtype

Location

Funder name

Kulturministeriet

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The primary paper of the project is expected to by published by October 2019 in an internationally renowned journal.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.

Intention to publish date

01/10/2019

Participant level data

Other

Basic results (scientific)

Publication list

2020 results in https://www.ncbi.nlm.nih.gov/pubmed/32267714 (added 30/04/2020)

Publication citations

Additional files

Editorial Notes

30/04/2020: The following changes were made to the trial record: 1. Publication reference added. 2. The total final enrolment was added. 18/06/2019: Trial’s existence confirmed by Aase og Ejnar Danielsens Fond.