Testing of a Valsalva Assist Device (VAD) in Healthy Volunteers Performing a Valsalva Manoeuvre

• Sponsor: University of Exeter (Other)
• Overall Status: Completed
• CT.gov ID: NCT03298880
• Collaborator: Royal Devon and Exeter NHS Foundation Trust (Other)
• Enrollment: 75
• Location: 1
• Arm: 1
• Actual Duration (Months): 3.2
• Patients Per Site Per Month: 23.8

Study Details

Study Description

Brief Summary

A prototype for a Valsalva Assist Device (VAD), which provides resistance to exhalation, has been developed and is ready for testing in healthy volunteers. There is a need to ensure the device can deliver the required strain and evaluate the physiological response (lowered heart rate) when used to deliver a Valsalva manoeuvre (VM) with and without postural modification.

Condition or Disease	Intervention/Treatment	Phase
SVT; Vagal Bradycardia	Device: Supine VM VAD; Device: Supine VAD manometer; Other: Modified VM VAD; Other: Modified VM Manonmeter	N/A

Detailed Description

The aim of this study is to evaluate the performance of a novel Valsalva assist device (VAD) in healthy volunteer and to confirm the physiological effects of a modified VM.

Specific Objectives:

To measure and compare peak strain pressure and duration produced using the device compared to a standard manometer in supine and modified postures

To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy volunteers performing a VM using the VAD versus manometer.

To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy volunteers performing a modified VM versus a standard supine VM using the VAD.

To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy volunteers performing a modified VM versus a standard supine VM using a manometer.

The investigators will conduct a single centre repeated measures observational study of use of the device to generate a Valsalva strain in a sample of healthy adult volunteers from the University of Exeter or RD&E Hospital staff. All participants will be screened for eligibility and undergo informed written consent prior to participation. If participants fail screening due to abnormal clinical readings or vital signs, the chief investigator will review them, any urgent abnormalities (very unlikely) would be reviewed by the chief investigator or delegated emergency department doctor as soon as they are discovered. Depending on the severity, if treatment is required urgently then they will be treated in the emergency department. Otherwise, they will be referred back to their GP. Potential participants will be given written information about the study at least 24 hours prior to recruitment and interested individuals invited to attend screening, recruitment and testing.

Potential participants will be invited to express an interest in taking part by responding to the trial poster. These posters will be displayed in the medical student common rooms ED department notice board. The potential participant contacts the researcher leading the practical aspects of the trial by phone or email. Respondents will be asked how they would like to receive further information (post, email, and phone) and offered an appointment at the Clinical Research Facility (CRF) for screening and written consent if eligible, at their convenience but at least 24 hours after receiving the information sheet. Given the simple, safe and quick nature of the interventions, participants will be given the choice to take part after written consent or to return on another date, whichever they would prefer, to ensure minimal visits whilst giving participants further time to consider taking part should they wish.

The VM is an extremely safe, physiological manoeuvre which is used in everyday life (eg straining at stool) and has been used in trial conditions and clinical practice many thousands of times with no serious adverse events. The investigators will exclude participants who could conceivably be at any risk of harm from performing a VM or from the use of the device.

The screening will include 12 lead ECG and physical examination including observations of heart rate, oxygen saturations, respiratory rate and blood pressure. Any participants with any detected abnormalities, whether they are excluded from participation or not, will be informed and referred to their primary care physician as appropriate. All testing will be conducted in the clinical research facility (CRF) of the Royal Devon & Exeter Hospital, according to a strict trial protocol.

Test Valsalva Manoeuvres:

Participants will undergo a total of 4 VMs of the following 4 variations in random order, stratified by method of strain generation to ensure balance between the order of manometer and device use:

1. Supine VM using a manometer. Supine Valsalva strain using a manometer visible to the participant with a target of 40mmHg for 15 seconds

2. Supine VM using the device. Supine Valsalva strain using the device connected to manometer invisible to the participant but visible to a researcher for 15 seconds

3. Modified VM using a manometer. Semi-recumbent (at 45 degrees) Valsalva stain using a manometer visible to the participant with a target of 40mmHg for 15 seconds followed by supine positioning and passive 45-degree leg lift immediately at the end of the strain for a further 15 seconds (the modified VM)

4. Modified VM using the device. Semi-recumbent (at 45 degrees) Valsalva strain using the device connected to manometer invisible to the participant but visible to a researcher for 15 seconds followed by supine positioning and passive 45-degree leg lift immediately at the end of the strain for a further 15 seconds (the modified VM)

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Four repeated measures in each participant in random orderFour repeated measures in each participant in random order
• Masking: None (Open Label)
• Masking Description: Participants will not be able see manometer when using VAD Analysis of ECG traces will be blind to intervention as traces will be marked with a code, interventions carried out in random order and analysed in batches
• Primary Purpose: Other
• Official Title: Testing of a Valsalva Assist Device (VAD) to Assess Effects on Vagal Tone and Strain Pressures Achieved Compared to a Standard Manometer in Healthy Volunteers Performing Standard and Modified Valsalva Manoeuvres.
• Actual Study Start Date: Nov 1, 2017
• Actual Primary Completion Date: Feb 5, 2018
• Actual Study Completion Date: Feb 5, 2018

Arms and Interventions

Arm

Intervention/Treatment

Other: Four VM's Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter

Device: Supine VM VAD; Valsalva strain delivered using VAD; Other Names: Valsalva Assist Device supine ; Device: Supine VAD manometer; supine Valsalva strain delivered using manometer; Other Names: Valsalva Assist Device ; Other: Modified VM VAD; modified VM using VAD; Other Names: Standard (supine) position ; Other: Modified VM Manonmeter; Postural modified position VM using manometer; Other Names: Modified VM position

Outcome Measures

Primary Outcome Measures

1. Assessing Heart Rate During the Supine and Modified VM and Assessing Heart Rate While Using the VAD and Manometer [3 minutes (4 repetitions of 45 seconds)]

   Assessing the effects on heart rate of a supine valsalva manoeuvre compared to the modified Valsalva manoeuvres in healthy volunteers.The investigators will measure the longest RR (length between each r wave) length in mm during the 15 seconds during the manoeuvre and the 15 seconds afterwards on an 3 lead ECG trace. The investigators will measure pre strain heart rate using the 15 seconds of baseline heart rate before the maneouvre on the 3 lead ECG. Using an average of the RR length(mm). The heart rate in beats per minute will then be worked out using a calculation from the RR length. RR length (mm) x0.04 = RR in seconds. (10/RR in seconds)x60 = beats per minute. These arms are combined so as to make the data easier to understand. The higher the number the better the outcome. maximum score is minimum score is 25.9 with maximum 33.6

Secondary Outcome Measures

1. Percentage of Participants Who Acheived a 15 Second Strain Duration During a VM Comparing a Valsalva Assist Device and a Standard Manometer [1 minute (4 repetitions of 15 seconds)]

   The investigators measured the time each Valsalva manoeuvre managed to keep to a 15-second drain if they managed 15 seconds at a pressure of 35-45mmHg this would count as an achieved strain.

2. Peak Sustained Pressure Testing of a Valsalva Assist Device (VAD) Compared to the Standard Manometer [15 seconds (4 repetitions of 15 seconds)]

   The investigators will measure the highest pressure achieved for more than a second using a manometer in mmHg and compare these done with the VAD and the manometer

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Adult Volunteers between 18 and 60 years old from University of Exeter or RD&E Hospital staff

• Sinus rhythm on initial ECG

• Self-reported good health

Exclusion Criteria:

• Any regular medication other than the oral contraceptive

• Previous cardiovascular or respiratory disease

• Any contraindication to performing a VM strain. (Eg. Known aortic stenosis, recent myocardial infarction, glaucoma, retinopathy)

• Pregnancy

• Any ECG abnormality

• Any contra-indication to postural modification (any reason the participant can't lie flat and have both legs lifted to 45 degrees, eg prosthetic hip

• Inability or refusal to give written consent to take part

• Observations of heart rate, oxygen saturations, respiratory rate or blood pressure outside the normal range. Specifically blood pressure less than 100 systolic

• Caffeinated drinks within 6 hours prior to testing

• The use of stimulant drugs or alcohol within 24 hours prior to testing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Devon & Exeter NHS FT	Exeter	Devon	United Kingdom	EX4 7DW

Sponsors and Collaborators

• University of Exeter
• Royal Devon and Exeter NHS Foundation Trust

Investigators

• Principal Investigator: Andrew Appelboam, MBBS, Royal Devon & Exeter Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 24, 2017
• Informed Consent Form - Nov 1, 2017

More Information

Publications

None provided.

• Responsible Party: University of Exeter
• ClinicalTrials.gov Identifier: NCT03298880
• Other Study ID Numbers: 1617/043
• First Posted: Oct 2, 2017
• Last Update Posted: Jun 10, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Exeter: Valsalva manoeuvre; Vagal tone; Modified Valsalva; Valsalva Assist Device
• Additional relevant MeSH terms: Bradycardia

Study Results

Participant Flow

Arm/Group Title	Four VM's
Arm/Group Description	Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter Supine VM VAD: Valsalva strain delivered using VAD Supine VAD manometer: supine Valsalva strain delivered using manometer Modified VM VAD: modified VM using VAD Modified VM Manonmeter: Postural modified position VM using manometer
Period Title: Overall Study
STARTED	75
COMPLETED	75
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Four VM's
Arm/Group Description	Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter Supine VM VAD: Valsalva strain delivered using VAD Supine VAD manometer: supine Valsalva strain delivered using manometer Modified VM VAD: modified VM using VAD Modified VM Manonmeter: Postural modified position VM using manometer
Overall Participants	75
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	75 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	26.19
Sex: Female, Male (Count of Participants)
Female	45 60%
Male	30 40%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United Kingdom	75 100%

Outcome Measures

1. Primary Outcome

Title	Assessing Heart Rate During the Supine and Modified VM and Assessing Heart Rate While Using the VAD and Manometer
Description	Assessing the effects on heart rate of a supine valsalva manoeuvre compared to the modified Valsalva manoeuvres in healthy volunteers.The investigators will measure the longest RR (length between each r wave) length in mm during the 15 seconds during the manoeuvre and the 15 seconds afterwards on an 3 lead ECG trace. The investigators will measure pre strain heart rate using the 15 seconds of baseline heart rate before the maneouvre on the 3 lead ECG. Using an average of the RR length(mm). The heart rate in beats per minute will then be worked out using a calculation from the RR length. RR length (mm) x0.04 = RR in seconds. (10/RR in seconds)x60 = beats per minute. These arms are combined so as to make the data easier to understand. The higher the number the better the outcome. maximum score is minimum score is 25.9 with maximum 33.6
Time Frame	3 minutes (4 repetitions of 45 seconds)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mean Drop in Heart Rate Using the Modified VM	Mean Drop in Heart Rate of Supine VM	Mean Drop in Heart Rate Using VAD	Mean Drop in Heart Rate From Using the Manometer
Arm/Group Description	This measures the mean drop in heart rate before and after the modified valsalva manoeuvre using both the VAD and monometer	This measures the mean drop in heart rate before and after the supine valsalva manouevre using the both the VAD and monometer	This measures the mean drop in heart rate before and after healthy participants undertook the modified and supine Valsalva manoeuvres while using the VAD	This measures the mean drop in heart rate before and after healthy participants undertook the modified and supine Valsalva manoeuvres while using the manometer
Measure Participants	75	75	75	75
Mean (Full Range) [beat per minute]	33.6	25.9	28.7	30.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mean Drop in Heart Rate Using the Modified VM, Mean Drop in Heart Rate of Supine VM
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	mixed linear regression
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.7
	Confidence Interval	(2-Sided) 95%; 2.1 to 5.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.12
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mean Drop in Heart Rate Using the Modified VM, Mean Drop in Heart Rate of Supine VM
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	mixed linear regression
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.3
	Confidence Interval	(2-Sided) 95%; 0.8 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants Who Acheived a 15 Second Strain Duration During a VM Comparing a Valsalva Assist Device and a Standard Manometer
Description	The investigators measured the time each Valsalva manoeuvre managed to keep to a 15-second drain if they managed 15 seconds at a pressure of 35-45mmHg this would count as an achieved strain.
Time Frame	1 minute (4 repetitions of 15 seconds)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	% Who Achieved 15 Second Strain Using a VAD	% Who Achieved 15 Second Strain Using a Manometer
Arm/Group Description	percentage of participants utilising the Valsalva assist device to achieve a valsalva manoeuvre who achieved the full 15 second strain using the Valsalva assist device	percentage of participants utilising the manometer to achieve a valsalva manoeuvre who achieved the full 15 second strain using the manometer
Measure Participants	75	75
Count of Participants [Participants]	56 74.7%	73 NaN

3. Secondary Outcome

Title	Peak Sustained Pressure Testing of a Valsalva Assist Device (VAD) Compared to the Standard Manometer
Description	The investigators will measure the highest pressure achieved for more than a second using a manometer in mmHg and compare these done with the VAD and the manometer
Time Frame	15 seconds (4 repetitions of 15 seconds)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peak Pressures Acheived by VAD	Peak Pressures Acheived by Manometer
Arm/Group Description	peak pressure acheived by VAD	Peak pressures achieved by manometer
Measure Participants	75	75
Mean (Full Range) [mean (mmHg) of peak pressures acheived]	42.46	39.96

Adverse Events

Time Frame	15 minutes as each patient was taking part
Adverse Event Reporting Description	this was a very low risk study
Arm/Group Title	Four VM's
Arm/Group Description	Healthy volunteers undergo repeated VM's - Device: Supine VM VAD, Supine VAD manometer Modified VM VAD, Modified VM Manonmeter Supine VM VAD: Valsalva strain delivered using VAD Supine VAD manometer: supine Valsalva strain delivered using manometer Modified VM VAD: modified VM using VAD Modified VM Manonmeter: Postural modified position VM using manometer
All Cause Mortality
	Four VM's
	Affected / at Risk (%)	# Events
Total	0/75 (0%)
Serious Adverse Events
	Four VM's
	Affected / at Risk (%)	# Events
Total	0/75 (0%)
Other (Not Including Serious) Adverse Events
	Four VM's
	Affected / at Risk (%)	# Events
Total	17/75 (22.7%)
Nervous system disorders
headache	17/75 (22.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.