ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12617000983303

Ethics application status

Approved

Date submitted

30/06/2017

Date registered

10/07/2017

Date last updated

13/08/2019

Date data sharing statement initially provided

13/08/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The causes of bradycardia in athletes

Scientific title

The effects of ivabradine under autonomic blockade in endurance athletes.

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1198-5373

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Bradycardia in athletes

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Intervention:
Autonomic blockade with single doses of intravenous metoprolol(0.2mg/kg) + intravenous atropine (0.04mg/kg) plus oral ivabradine 15mg
Exposure: endurance sport participation
A wash out period of at least 24 hours will occur before crossover to the control arm

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Lifestyle

Comparator / control treatment

Control:
Autonomic blockade with single doses of intravenous metoprolol(0.2mg/kg) + intravenous atropine (0.04mg/kg) plus plus placebo (methylcellulose capsule)
Exposure control: non endurance sport athletes
A wash out period of at least 24 hours will occur before crossover to the
intervention arm

Control group

Placebo

Outcomes

Primary outcome [1]

Heart rate at rest on ECG

Timepoint [1]

30 minutes following administration of autonomic blockade + ivabradine or placebo

Primary outcome [2]

Peak heart rate on ECG monitoring

Timepoint [2]

During VO2 max test 30 minutes after administration of autonomic blockade + ivabradine or placebo (immediately after resting ECG)

Secondary outcome [1]

Change in left ventricular end diastolic volume on echocardiography at rest

Timepoint [1]

One hour following administration of autonomic blockade + ivabradine or placebo precrossover

Secondary outcome [2]

Change in BNP on serum assay post exercise

Timepoint [2]

Immediately following administration of autonomic blockade + ivabradine or placebo and VO2 max test

Secondary outcome [3]

Change in right ventricular end diastolic volume on echocardiography at rest

Timepoint [3]

One hour following administration of autonomic blockade + ivabradine or placebo pre crossover

Secondary outcome [4]

Change in left ventricular end diastolic volume on MRI at rest

Timepoint [4]

One hour following administration of autonomic blockade + ivabradine or placebo post cross over

Secondary outcome [5]

Change in right ventricular end diastolic volume on MRI at rest

Timepoint [5]

One hour following administration of autonomic blockade + ivabradine or placebo post cross over

Secondary outcome [6]

Change in right ventricular end diastolic volume on exercise MRI at maximal exercise

Timepoint [6]

One hour following administration of autonomic blockade + ivabradine or placebo post cross over (immediately post rest MRI)

Secondary outcome [7]

Change in right ventricular end diastolic volume on exercise MRI at maximal exercise

Timepoint [7]

One hour following administration of autonomic blockade + ivabradine or placebo post cross over (immediately post rest MRI)

Secondary outcome [8]

Change in right ventricular end diastolic volume on exercise echocardiography at maximal exercise

Timepoint [8]

One hour following administration of autonomic blockade + ivabradine or placebo pre crossover (immediately post rest echocardiogram)

Secondary outcome [9]

Change in left ventricular end diastolic volume on exercise echocardiography at maximal exercise

Timepoint [9]

One hour following administration of autonomic blockade + ivabradine or placebo pre crossover
(immediately post rest echocardiogram)

Secondary outcome [10]

Change in maximal left atrial volume on exercise echocardiography at maximal exercise

Timepoint [10]

One hour following administration of autonomic blockade + ivabradine or placebo pre crossover
(immediately post rest echocardiogram)

Secondary outcome [11]

Change in maximal left atrial volume on exercise MRI at maximal exercise

Timepoint [11]

One hour following administration of autonomic blockade + ivabradine or placebo post crossover
(immediately post rest MRI)

Secondary outcome [12]

Change in PA pressure as measured by measuring tricupsid regurgitation velocity during maximal exercise on exercise echocardiography

Timepoint [12]

One hour following administration of autonomic blockade + ivabradine or placebo pre crossover
(immediately post rest echocardiogram)

Eligibility

Key inclusion criteria

Group 1 (Endurance athletes): Competing in endurance sport
Group 2 (Healthy Volunteers): Less than three hours of exercise per week
Group 3 (Endurance athletes with bradycardia): Endurance athletes with a resting heart rate less than 40

Minimum age

18 Years

Maximum age

50 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Allergy to one of the medications
2. Asthma
3. Glaucoma
4. Urinary Retention/Prostate enlargement
5. Past history of psychosis
6. Ulcerative Colitis
7. Gastrointestinal Obstruction
8. Myasthenia gravis
9. Hypotension(low blood pressure
10. Smoker
11. Preexisting cardiac or lung disease
12. Pregnant or breast feeding
13. Contraindication to MRI

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Numbered containers

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes

Intervention assignment

Crossover

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

The group sizes were calculated to be able to detect a change in heart rate of 10 beats per minute.
Baseline comparisons of continuous variables will be made between groups using independent samples t-tests. Categorical value comparisons will be made using chi square testing. Repeated measures will be analysed using repeated measures ANOVA.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

10/07/2017

Actual

18/07/2017

Date of last participant enrolment

Anticipated

23/09/2019

Actual

Date of last data collection

Anticipated

30/09/2019

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Baker Heart and Diabetes Institute - Melbourne

Recruitment postcode(s) [1]

3004 - Melbourne

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC

Address [1]

GPO Box 1421
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Other

Name

Baker Heart and Diabetes Institute

Address

PO Box 6492, Melbourne Victoria 3004, Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

Old Baker Building, Level 1,
55 Commercial Rd, Melbourne VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/03/2017

Approval date [1]

10/05/2017

Ethics approval number [1]

138/17

Summary

Brief summary

It is well known that athletes have lower heart rates (bradycardia) than non-athletes. This is generally considered a healthy adaptation. However, bradycardia has been associated with the subsequent development of atrial fibrillation (AF), an arrhythmia known to increase the risk of heart failure, stroke and even death. Consequently, bradycardia could conceivably be associated with significant problems later in life.

The reasons athletes have slow heart rates are not well understood. Traditionally changes in neural input (vagal tone) were thought to lead to bradycardia in athletes. However, several studies have demonstrated that even after blocking these inputs(autonomic blockade), athletes continue to have lower heart rates than non-athletes. The reasons for this are not known however recent research using athlete mice models suggests this is due to intrinsic changes within the heart by downregulation of the HCN4 gene. In the mouse model, the medication which blocks this gene, ivabradine, helped to equalize the heart rates in athlete and non-athlete mice. 

Our aim in this study is to understand the reason for lower heart rates in endurance athletes. Participants will undergo repeat testing under experimental conditions to help determine the causes of low heart rates in athletes.

We hypothesize that ivabradine will be less effective in athletes, ie it will lower the heart rate of athletes less than nonathletes. This would suggest that bradycardia in athletes is associated with changes within the heart rather than reversible changes in neural inputs. This may provide some insights into the mechanism of atrial fibrillation in athletes.

Trial website

https://www.baker.edu.au/research/clinical-trials/endurance-athletes

Trial related presentations / publications

Public notes

Attachments [1]

/AnzctrAttachments/373222-Advertisement V4 4.12.17.pdf (Other)

Contacts

Principal investigator

Name

A/Prof Andre La Gerche

Address

Baker Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne, VIC 3004

Country

Australia

Phone

+61 3 8532 1143

Fax

andre.lagerche@baker.edu.au

Contact person for public queries

Name

Darragh Flannery

Address

Baker Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne, VIC 3004

Country

Australia

Phone

+61 3 8532 1214

Fax

darragh.flannery@baker.edu.au

Contact person for scientific queries

Name

Andre La Gerche

Address

Baker Heart and Diabetes Institute
Level 4, Alfred Centre
99 Commercial Road
Melbourne, VIC 3004

Country

Australia

Phone

+ 61 3 8532 1143

Fax

andre.lagerche@baker.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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