Hypertrophic CardiomyopathyPhase 1NCT00504647
Biventricular Pacing in Hypertrophic Cardiomyopathy
A Phase 1 study testing Biventricular Pacemaker in people with Hypertrophic Cardiomyopathy, run by University Hospital Birmingham at 3 sites in United Kingdom.
Trial summary
Hypertrophic Cardiomyopathy is an inherited condition characterized by thickening (hypertrophy) of the heart muscle. Many patients who have this condition have a reduced ability to exercise because of breatlessness, which can in some cases be severe. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Hypertrophic Cardiomyopathy
- What is being tested?
- Biventricular Pacemaker
- Type of treatment
- Medical device
- How many people
- 30 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Jun 2006to Aug 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of Hypertrophic Cardiomyopathy
- Ability to perform peak exercise oxygen consumption test.
Who cannot join
- Left ventricular outflow tract gradient more than 30mmHg
- Peak Oxygen consumption more than 75% of maximum predicted.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Recruiting
The Queen Elizabeth, University Hospital Birmingham
Birmingham, B15 2TH
- Recruiting
University Hospital of Wales
Cardiff, CF14 4XW
- Recruiting
The Heart Hospital
London, W1G 8PH
About this study
Official title: Diastolic Ventricular Interaction and the Effects Of Biventricular Pacing in Hypertrophic Cardiomyopathy
Hypertrophic Cardiomyopathy is an inherited condition characterized by thickening (hypertrophy) of the heart muscle. Many patients who have this condition have a reduced ability to exercise because of breatlessness, which can in some cases be severe. This appears in most cases to be due to an impairment of the filling of the heart, especially on exercise this limits the amount of blood the heart is able to pump. Several factors may contribute to this slow filling of the heart, including (1) The heart contracts and relaxes in an incoordinate way (called 'dyssynchrony') which is inefficient, and (2) The filling of the main pumping chamber (the left ventricle) may be impeded by high pressure in the other ventricle(the right ventricle)- in other words the left ventricle is 'squashed' by the right ventricle. This is known as diastolic ventricular interaction.
Although drugs can improve the filling of the heart and relieve symptoms, some patients remain very symptomatic despite these drugs.
Read more
The mechanisms responsible for the filling abnormality in patients with Hypertrophic Cardiomyopathy are similar to those seen in the much more common condition known as Heart Failure. A special type of pacemaker technique called 'Biventricular Pacing' has been shown to markedly improve symtoms in patients with heart failure. This form of pacing has been shown to improve both 'dyssynchrony' ( incoordination) and 'ventricular interaction' (squashed left heart) in patients with Heart Failure.
We propose that Biventricular pacing may similarly improve these abnormalities in patients with Hypertrophic Cardiomyopathy, resulting in an improvement of symptoms. The study will focus on patients with the condition who have severe symtoms despite being on optimal currently available drug therapy.
Read the detailed description
SUBJECTS Forty Participants, who fufil the entry criteria, will be selected. These Participants will be recruited from Cardiomyopathy clinics run at two sites. These are the Cardiomyopathy Clinics at the Heart Hospital, University College London, and from the Queen Elizabeth Hospital, Birmingham.
CONSENT Written informed consent will be obtained from all participants.
CLINICAL ASSESSMENT
A History will be taken and a Clinical Examination will be carried out. A validated Quality of life questionaire will be completed ( Minnesota Living with Heart Failure).
Maximal Cardiopulmonary exercise testing will be performed on a treadmill, with breath by breath respiratory gas sampling, using a face mask.
A 12 lead ECG will be obtained. 48hr Ambulatory Heart Rhythm Monitoring
CARDIAC ULTRASOUND SCAN ASSESSMENT
To assess the function of the Heart during its contraction and filling phases, including the degree of incoordination of the Heart muscle.
PACEMAKER IMPLANTATION
A pacemaker capable of Biventricular pacing will be implanted, using a standard established technique at one of three sites ( The Heart Hospital London, St Peters Hospital Chertsey, or Queen Elizabeth Hospital Birmingham ).
24hr POST PACEMAKER IMPLANT. Assessment of mechanical dyssynchrony will be made using Ultrasound techniques which will include 2D/ M mode Echocardiography, Doppler studies, and Tissue doppler imaging. This assessment will be made with the Pacemaker off, and in Left and Right heart pacing mode.
HAEMODYNAMIC STUDIES
These will be carried out approximately two weeks following pacemaker implantation.
The test will involve Nuclear Heart Scans (Gated Equilibrium Radionuclide Ventriculography) and Acute Volume Unloading of the right and left heart chambers.
This will be carried out at the University Of Birmingham, Department of Cardiovascular Sciences We shall apply these techniques while the heart is paced in four different modes.
The nuclear heart scan is a method by which we can measure the volume of the left heart chamber. The study will involve the placement of small needle into a vein of the patients forearm. Through this we will inject a primer which will make participants red blood cells very sticky. After twenty minutes we will take a blood sample from the same needle. This sample of blood will be mixed with a radioactive tracer. The tracer will be re-injected through the same needle into the participants' vein. This tracer will allow us to measure the amount of blood inside the chambers of the participants' heart with a special camera, a gamma camera. The pictures will be taken with the participants lying on a bed throughout.
The bed we will ask participants to lie on is called a Lower Body Negative Pressure Bed. When lying on this bed the participants' legs will be inside a see through plastic dome. A belt will be placed around the participants' waist in order to create an airtight seal around their legs. The bed is attached to a vacuum that allows us to create a low pressure environment around participants' legs. This causes blood to pool inside the veins of participants' legs. This leads to Acute Volume unloading of the right and left heart chambers.
Once participants have received the injection of the radioactive tracer and are lying comfortably in the Lower Body Negative Pressure Bed we will then take measurements of the amount of blood in the participants' heart. We shall do this using the special camera.
We shall take measurements with the pacemaker in its four different pacemaker modes, and then repeat these measurements but this time with a low pressure environment produced around participants' legs in order to reduce the pressure on your heart. The test is painless apart from mild discomfort from placing one needle at the beginning. The whole test will take between one and one and half hours.
The method of administration has been performed safely by our team for a number of years now.
After a 1 hour break the Participants will do Exercise component of the Nuclear Heart Scan. This component of the study will involve no further doses of radiation, and no new needles.
Participants will be asked to lie, semi-erect, on an exercise bed for up to 90 minutes. The exercise will be in the form of a pedal bike. The pacemaker will be programmed into four different modes of heart pacing. Whilst in each mode participants will be asked to exercise to three different stages of exercise. Each stage will last 4 minutes. The levels of difficulty will be worked out from a treadmill exercise test completed by the participants prior to the pacemaker implantation. Participants will be allowed to rest between each stage of exercise. If participants complete the whole study they will have cycled for a total of 48 minutes. During each stage 4ml of blood will be taken from the needle that will have been placed in a vein during the earlier part of the study.
During each stage of exercise an image of the heart will be taken with the gamma camera, as done earlier in the study.
From these measurements we will be able to calculate the effect of the different pacing modes on the ability of the heart to pump blood on exercise.
Participants are free to stop the exercise at any time they feel they cannot continue.
RANDOMISATION AND FOLLOW UP. Following pacemaker implant, pressure studies, and Ultrasound assessment, participants will be randomized in a double blind fashion to have their pacemaker programmed to either one of the following (1) Pacemaker Off mode, ( 2 ) Left and Right Heart chamber pacemaker mode. The Participants will be paced in that specific mode for four months before repeat Clinical and Cardiac Ultrasound assessments. The mode of pacing will then be changed, and maintained for a further four months, before repeat Clinical and Ultrasound assessment. The pacing mode will be randomly selected, but no pacing mode will be repeated in any one participant. The participant and the member of the research team performing the Clinical and Ultrasound assessment of the participant, shall be blinded to the pacemaker mode.
- Conditions
- Hypertrophic Cardiomyopathy
- Being tested
- Biventricular Pacemaker
- Keywords
- Hypertrophic, Cardiomyopathy, Diastolic, Ventricular, Interaction, Biventricular, Pacemaker
- Medical subject headings
- Cardiomyopathy, Hypertrophic, Hypertrophy, Cardiomyopathies, Heart Murmurs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biventricular PacemakerDevice
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Exercise Oxygen Consumption.
Measured: 4 month
Secondary outcomes (2)
Myocardial Asynchrony Index
Measured: 4 months
Minnesota Quality of Life Questionnaire
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2007 (estimated)
- Study startJun 2006
- Study completionAug 2008 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypertrophic CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- British Heart Foundation, Medtronic
- Investigators
- Michael P Frenneaux, MBBS(Hons), Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00504647
- Sponsor's protocol ID
- 05/Q2707/352
- Status last verified
- Jul 2007
- First submitted
- 18 Jul 2007
- Last updated
- 20 Jul 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Ahmed I, Loudon BL, Abozguia K, Cameron D, Shivu GN, Phan TT, Maher A, Stegemann B, Chow A, Marshall H, Nightingale P, Leyva F, Vassiliou VS, McKenna WJ, Elliott P, Frenneaux MP. Biventricular pacemaker therapy improves exercise capacity in patients with non-obstructive hypertrophic cardiomyopathy via augmented diastolic filling on exercise. Eur J Heart Fail. 2020 Jul;22(7):1263-1272. doi: 10.1002/ejhf.1722. Epub 2020 Jan 23.
PubMed 31975494
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diastolic Ventricular Interaction and the Effects Of Biventricular Pacing in Hypertrophic Cardiomyopathy
- ClinicalTrials.gov ID
- NCT00504647
- Acronym / sponsor ID
- 05/Q2707/352
- Conditions
- Hypertrophic Cardiomyopathy
- Keywords
- Hypertrophic, Cardiomyopathy, Diastolic, Ventricular, Interaction, Biventricular, Pacemaker
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital BirminghamUniversity, hospital or other
- Collaborators
- British Heart Foundation, Medtronic
- Study start
- Jun 2006
- Study completion
- Aug 2008 (estimated)
- First posted
- 20 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypertrophic Cardiomyopathy is an inherited condition characterized by thickening (hypertrophy) of the heart muscle. Many patients who have this condition have a reduced ability to exercise because of breatlessness, which can in some cases be severe. This appears in most cases to be due to an impairment of the filling of the heart, especially on exercise this limits the amount of blood the heart is able to pump. Several factors may contribute to this slow filling of the heart, including (1) The heart contracts and relaxes in an incoordinate way (called 'dyssynchrony') which is inefficient, and (2) The filling of the main pumping chamber (the left ventricle) may be impeded by high pressure in the other ventricle(the right ventricle)- in other words the left ventricle is 'squashed' by the right ventricle. This is known as diastolic ventricular interaction.
Although drugs can improve the filling of the heart and relieve symptoms, some patients remain very symptomatic despite these drugs.
The mechanisms responsible for the filling abnormality in patients with Hypertrophic Cardiomyopathy are similar to those seen in the much more common condition known as Heart Failure. A special type of pacemaker technique called 'Biventricular Pacing' has been shown to markedly improve symtoms in patients with heart failure. This form of pacing has been shown to improve both 'dyssynchrony' ( incoordination) and 'ventricular interaction' (squashed left heart) in patients with Heart Failure.
We propose that Biventricular pacing may similarly improve these abnormalities in patients with Hypertrophic Cardiomyopathy, resulting in an improvement of symptoms. The study will focus on patients with the condition who have severe symtoms despite being on optimal currently available drug therapy.
Detailed description
SUBJECTS Forty Participants, who fufil the entry criteria, will be selected. These Participants will be recruited from Cardiomyopathy clinics run at two sites. These are the Cardiomyopathy Clinics at the Heart Hospital, University College London, and from the Queen Elizabeth Hospital, Birmingham.
CONSENT Written informed consent will be obtained from all participants.
CLINICAL ASSESSMENT
A History will be taken and a Clinical Examination will be carried out. A validated Quality of life questionaire will be completed ( Minnesota Living with Heart Failure).
Maximal Cardiopulmonary exercise testing will be performed on a treadmill, with breath by breath respiratory gas sampling, using a face mask.
A 12 lead ECG will be obtained. 48hr Ambulatory Heart Rhythm Monitoring
CARDIAC ULTRASOUND SCAN ASSESSMENT
To assess the function of the Heart during its contraction and filling phases, including the degree of incoordination of the Heart muscle.
PACEMAKER IMPLANTATION
A pacemaker capable of Biventricular pacing will be implanted, using a standard established technique at one of three sites ( The Heart Hospital London, St Peters Hospital Chertsey, or Queen Elizabeth Hospital Birmingham ).
24hr POST PACEMAKER IMPLANT. Assessment of mechanical dyssynchrony will be made using Ultrasound techniques which will include 2D/ M mode Echocardiography, Doppler studies, and Tissue doppler imaging. This assessment will be made with the Pacemaker off, and in Left and Right heart pacing mode.
HAEMODYNAMIC STUDIES
These will be carried out approximately two weeks following pacemaker implantation.
The test will involve Nuclear Heart Scans (Gated Equilibrium Radionuclide Ventriculography) and Acute Volume Unloading of the right and left heart chambers.
This will be carried out at the University Of Birmingham, Department of Cardiovascular Sciences We shall apply these techniques while the heart is paced in four different modes.
The nuclear heart scan is a method by which we can measure the volume of the left heart chamber. The study will involve the placement of small needle into a vein of the patients forearm. Through this we will inject a primer which will make participants red blood cells very sticky. After twenty minutes we will take a blood sample from the same needle. This sample of blood will be mixed with a radioactive tracer. The tracer will be re-injected through the same needle into the participants' vein. This tracer will allow us to measure the amount of blood inside the chambers of the participants' heart with a special camera, a gamma camera. The pictures will be taken with the participants lying on a bed throughout.
The bed we will ask participants to lie on is called a Lower Body Negative Pressure Bed. When lying on this bed the participants' legs will be inside a see through plastic dome. A belt will be placed around the participants' waist in order to create an airtight seal around their legs. The bed is attached to a vacuum that allows us to create a low pressure environment around participants' legs. This causes blood to pool inside the veins of participants' legs. This leads to Acute Volume unloading of the right and left heart chambers.
Once participants have received the injection of the radioactive tracer and are lying comfortably in the Lower Body Negative Pressure Bed we will then take measurements of the amount of blood in the participants' heart. We shall do this using the special camera.
We shall take measurements with the pacemaker in its four different pacemaker modes, and then repeat these measurements but this time with a low pressure environment produced around participants' legs in order to reduce the pressure on your heart. The test is painless apart from mild discomfort from placing one needle at the beginning. The whole test will take between one and one and half hours.
The method of administration has been performed safely by our team for a number of years now.
After a 1 hour break the Participants will do Exercise component of the Nuclear Heart Scan. This component of the study will involve no further doses of radiation, and no new needles.
Participants will be asked to lie, semi-erect, on an exercise bed for up to 90 minutes. The exercise will be in the form of a pedal bike. The pacemaker will be programmed into four different modes of heart pacing. Whilst in each mode participants will be asked to exercise to three different stages of exercise. Each stage will last 4 minutes. The levels of difficulty will be worked out from a treadmill exercise test completed by the participants prior to the pacemaker implantation. Participants will be allowed to rest between each stage of exercise. If participants complete the whole study they will have cycled for a total of 48 minutes. During each stage 4ml of blood will be taken from the needle that will have been placed in a vein during the earlier part of the study.
During each stage of exercise an image of the heart will be taken with the gamma camera, as done earlier in the study.
From these measurements we will be able to calculate the effect of the different pacing modes on the ability of the heart to pump blood on exercise.
Participants are free to stop the exercise at any time they feel they cannot continue.
RANDOMISATION AND FOLLOW UP. Following pacemaker implant, pressure studies, and Ultrasound assessment, participants will be randomized in a double blind fashion to have their pacemaker programmed to either one of the following (1) Pacemaker Off mode, ( 2 ) Left and Right Heart chamber pacemaker mode. The Participants will be paced in that specific mode for four months before repeat Clinical and Cardiac Ultrasound assessments. The mode of pacing will then be changed, and maintained for a further four months, before repeat Clinical and Ultrasound assessment. The pacing mode will be randomly selected, but no pacing mode will be repeated in any one participant. The participant and the member of the research team performing the Clinical and Ultrasound assessment of the participant, shall be blinded to the pacemaker mode.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Clinical diagnosis of Hypertrophic Cardiomyopathy
- Ability to perform peak exercise oxygen consumption test.
Key exclusion criteria (2 listed)
- Left ventricular outflow tract gradient more than 30mmHg
- Peak Oxygen consumption more than 75% of maximum predicted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biventricular Pacemaker | Device | – |
Primary outcome
Peak Exercise Oxygen Consumption.
Time frame: 4 month
2 secondary outcomes
Myocardial Asynchrony Index
Time frame: 4 months
Minnesota Quality of Life Questionnaire
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2007.
- Derived from this study: PubMed 31975494Ahmed I, Loudon BL, Abozguia K, Cameron D, Shivu GN, Phan TT, Maher A, Stegemann B, Chow A, Marshall H, Nightingale P, Leyva F, Vassiliou VS, McKenna WJ, Elliott P, Frenneaux MP. Biventricular pacemaker therapy improves exercise capacity in patients with non-obstructive hypertrophic cardiomyopathy via augmented diastolic filling on exercise. Eur J Heart Fail. 2020 Jul;22(7):1263-1272. doi: 10.1002/ejhf.1722. Epub 2020 Jan 23.
Related trials for Hypertrophic Cardiomyopathy
Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
RecruitingPhase 1
Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HTX-001
Nonobstructive Hypertrophic Cardiomyopathy
Recruiting
Positron Emission Tomography to Assess the Effect of Camzyos on Ischaemia in HOCM: PEACH Trial
Hypertrophic Obstructive Cardiomyopathy \(HOCM\), Left Ventricular Outflow Tract Obstruction
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael P Frenneaux, MBBS(Hons) principal investigator
University of Birmingham
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Biventricular Pacemaker in people with Hypertrophic Cardiomyopathy, run by University Hospital Birmingham at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Jul 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ibrar Ahmed, MBChB (44(0) 121 414 5916, 01ahmedi@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Exercise Oxygen Consumption. (time frame: 4 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00504647, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2007.