Heart FailureAMENDNCT02116140
ASV Effects on Myocardial Energetics and Sympathetic Nerve Function in Heart Failure and Sleep Apnea.
A study testing [C11]Acetate and HED PET in people with Heart Failure and Obstructive Sleep Apnea, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
Trial summary
Obstructive sleep apnea (OSA), central sleep apnea (CSA) and heart failure (HF) are states of metabolic demand and sympathetic nervous system (SNS) activation. In patients with sleep apnea and HF, continuous positive airway pressure (CPAP) initially may reduce left ventricular (LV)stroke volume (SV) but subsequently… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Obstructive Sleep Apnea, Central Sleep Apnea
- What is being tested?
- [C11]Acetate and HED PET
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2012to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- American Heart Association (AHA) Stages B, C and D heart failure due to ischemic, idiopathic or hypertensive causes with;
- systolic dysfunction, ejection fraction (EF) ≤45% by echocardiography
- optimal medical therapy conforming to the AHA guidelines (and for this proposal, stable therapy for >4 weeks)
- sleep apnea with an Apnea/hypopnea Index ≥15, which will be divided into OSA (> 50% events obstructive), or CSA (> 50% of events central in nature)for patients with OSA, an Epworth Sleepiness Scale score of >10 and no or mild daytime sleepiness (by the International Classification of Sleep Disorders
- age >18 years;
- willingness to receive ASV therapy
- informed consent
Who cannot join
- Myocardial infarction, cardiac surgery or angioplasty within 3 months prior to enrollment,
- listed for heart transplantation,
- HF due to primary valvular heart disease,
- pregnancy
- current use of ASV or CPAP.
- awaiting revascularization;
Show all 11Show fewer
- previous cardiac transplant;
- life expectancy less than 6 months due to other co-morbidity;
- a large transmural scar defined on previous perfusion imaging (severe resting perfusion defect (<50% uptake) occupying >25% of the LV);
- concomitant treatment or use of: tricyclic antidepressants, cocaine or drugs which may alter catecholamine uptake.
- For heart rate variability (HRV) analysis additional exclusions will include: a) a permanent pacemaker; b) atrial fibrillation; c) significant ventricular arrhythmia or sinus node dysfunction; patients may be excluded from HRV analysis and still be eligible for the sub-study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Long Term Adaptive Servo Ventilation Therapy on Myocardial Energetics and Sympathetic Nerve Function in Heart Failure and Sleep Apnea. The AMEND Sub-study
Obstructive sleep apnea (OSA), central sleep apnea (CSA) and heart failure (HF) are states of metabolic demand and sympathetic nervous system (SNS) activation. In patients with sleep apnea and HF, continuous positive airway pressure (CPAP) initially may reduce left ventricular (LV)stroke volume (SV) but subsequently improves and LV function. This may relate to an early beneficial effect on myocardial energetics through early reduction in metabolic demand that subsequently leads to improved efficiency of LV contraction. However, it is not clear whether long-term adaptive servo-ventilation (ASV) favorably affects cardiac energetics. Any such benefit may also relate to reduced sympathetic nervous system (SNS) activation. However its effect on myocardial SNS function is also not well studied.
In a pilot study we demonstrated early (6 week) beneficial effects of CPAP in patients with OSA and HF. The current proposal (AMEND) is a unique substudy of the recently funded ADVENT-HF trial (Adaptive Servo Ventilation for Therapy of Sleep Apnea in HeartFailure) (NCT01128816; CIHR; D. Bradley, PI).
Read more
We propose to evaluate the long-term (6 month) effects of ASV on daytime 1) oxidative metabolism; 2) the work metabolic index (WMI) as an estimate of mechanical efficiency; 3) myocardial sympathetic nerve (SN) pre-synaptic function; and 4) heart rate (HR) variability in patients with HF and coexisting OSA or CSA. In conjunction with echocardiographic measures of LV stroke work, positron emission tomography (PET) derived [11C] acetate kinetics will be used as a measure of oxidative metabolism, to determine the WMI. [11C] hydroxyephedrine (HED) retention will be used to measure cardiac SN pre-synaptic function.
Primary Hypotheses: In patients with chronic stable HF and CSA or OSA without excessive daytime sleepiness (EDS), long-term (6-month) ASV therapy yields:
- Beneficial effects on daytime myocardial metabolism leading to a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging;
- Improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index.
Read the detailed description
DEFINITIONS Obstructive sleep apnea (OSA) is characterized by: episodes of partial or complete pharyngeal collapse leading to obstructive hypopnea and apnea during sleep. OSA often coexists with HF.
Central sleep apnea (CSA) is characterized by: reductions in central respiratory drive during sleep that leads to episodes of partial or complete cessation of airflow. CSA often co-exists with HF.
Continuous positive airway pressure(CPAP) delivers air through a nasal or oral interface to preserve upper airway patency. It is a treatment for symptomatic OSA or some patients with CSA.
Adaptive Servoventilation (ASV) is effective in alleviating OSA and CSA. It provides expiratory positive pressure to alleviate OSA, and inspiratory positive airway pressure to eliminate CSA.
Oxidative metabolism: utilization of substrates via the tricarboxylic acid cycle for Adenosine triphosphate (ATP) production; it is linked to myocardial oxygen consumption and can be measured with [11C]acetate PET.
The work-metabolic index (WMI) is the external work (minute-work) of the left ventricle corrected for the rate of oxidative metabolism and is an estimate of mechanical efficiency.
Myocardial sympathetic neuron (SN) presynaptic function is the measure of uptake and storage of neuronal catecholamines in the heart measured by [11C]hydroxyephedrine (HED) PET.
- Conditions
- Heart Failure, Obstructive Sleep Apnea, Central Sleep Apnea
- Being tested
- [C11]Acetate and HED PET
- Keywords
- positron emission tomography, [11C]hydroxyephedrine (HED), [11C]acetate, Adaptive Servoventilation (ASV), Myocardial Energetics, work-metabolic index (WMI), Myocardial sympathetic neuron (SN) presynaptic function continuous positive airway pressure, heart rate variability, overnight polysomnogram, Plasma Norepinephrine, Urine Normetanephrine, Quality of Life
- Medical subject headings
- Heart Failure, Sleep Apnea, Obstructive, Sleep Apnea, Central
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[C11]Acetate and HED PETOther
| Study group | Role | What they receive |
|---|---|---|
| [C11]Acetate HED PET | Experimental | AMEND is a single centre substudy of the ADVENT-HF trial. This substudy is a clinical physiologic proposal designed to determine the effects of long-term (6 months) ASV on cardiac energetics and SN function in patients with chronic stable HF and sleep apnea extending our previous evaluation of short-term CPAP in patients with OSA and HF.
All subjects consenting to the ADVENT primary trial will be eligible to participate in the substudy.
Substudy consenting patients will have [11C]acetate and [11C]HED PET imaging; HR variability; plasma norepinephrine (NE) levels, urine normetanephrine levels within 2 weeks of the sleep study. Baseline measurements will be repeated after 6 months in all patients. Receives: Other: [C11]Acetate and HED PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
ASV therapy yields a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging in patients with HF, OSA and/or CSA
Measured: 6 months
ASV therapy yields an improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index inpatients with HF, OSA and/or CSA.
Measured: 6 months
Secondary outcomes (2)
ASV for CSA or OSA in patients with HF and sleep apnea will normalize daytime myocardial SN pre-synaptic function measured by [11C]HED retention on PET imaging,
Measured: 6 months
ASV for CSA or OSA in patients with HF and sleep apnea will normalize daytime sympathetic contributions to heart rate variability
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2014 (estimated)
- Study startJul 2012
- Primary completionJun 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rob S Beanlands, MD, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02116140
- Sponsor's protocol ID
- 2011469-01
- Other IDs
- NA7158
- Acronym
- AMEND
- Status last verified
- Nov 2025
- First submitted
- 14 Apr 2014
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
Publications
Beanlands RS, Nahmias C, Gordon E, Coates G, deKemp R, Firnau G, Fallen E. The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study. Circulation. 2000 Oct 24;102(17):2070-5. doi: 10.1161/01.cir.102.17.2070.
PubMed 11044422Yoshinaga K, Burwash IG, Leech JA, Haddad H, Johnson CB, deKemp RA, Garrard L, Chen L, Williams K, DaSilva JN, Beanlands RS. The effects of continuous positive airway pressure on myocardial energetics in patients with heart failure and obstructive sleep apnea. J Am Coll Cardiol. 2007 Jan 30;49(4):450-8. doi: 10.1016/j.jacc.2006.08.059.
PubMed 17258090
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Long Term Adaptive Servo Ventilation Therapy on Myocardial Energetics and Sympathetic Nerve Function in Heart Failure and Sleep Apnea. The AMEND Sub-study
- ClinicalTrials.gov ID
- NCT02116140
- Acronym / sponsor ID
- AMEND / 2011469-01
- Conditions
- Heart Failure, Obstructive Sleep Apnea, Central Sleep Apnea
- Keywords
- positron emission tomography, [11C]hydroxyephedrine (HED), [11C]acetate, Adaptive Servoventilation (ASV), Myocardial Energetics, work-metabolic index (WMI), Myocardial sympathetic neuron (SN) presynaptic function continuous positive airway pressure, heart rate variability
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 16 Apr 2014 (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.
Obstructive sleep apnea (OSA), central sleep apnea (CSA) and heart failure (HF) are states of metabolic demand and sympathetic nervous system (SNS) activation. In patients with sleep apnea and HF, continuous positive airway pressure (CPAP) initially may reduce left ventricular (LV)stroke volume (SV) but subsequently improves and LV function. This may relate to an early beneficial effect on myocardial energetics through early reduction in metabolic demand that subsequently leads to improved efficiency of LV contraction. However, it is not clear whether long-term adaptive servo-ventilation (ASV) favorably affects cardiac energetics. Any such benefit may also relate to reduced sympathetic nervous system (SNS) activation. However its effect on myocardial SNS function is also not well studied.
In a pilot study we demonstrated early (6 week) beneficial effects of CPAP in patients with OSA and HF. The current proposal (AMEND) is a unique substudy of the recently funded ADVENT-HF trial (Adaptive Servo Ventilation for Therapy of Sleep Apnea in HeartFailure) (NCT01128816; CIHR; D. Bradley, PI).
We propose to evaluate the long-term (6 month) effects of ASV on daytime 1) oxidative metabolism; 2) the work metabolic index (WMI) as an estimate of mechanical efficiency; 3) myocardial sympathetic nerve (SN) pre-synaptic function; and 4) heart rate (HR) variability in patients with HF and coexisting OSA or CSA. In conjunction with echocardiographic measures of LV stroke work, positron emission tomography (PET) derived [11C] acetate kinetics will be used as a measure of oxidative metabolism, to determine the WMI. [11C] hydroxyephedrine (HED) retention will be used to measure cardiac SN pre-synaptic function.
Primary Hypotheses: In patients with chronic stable HF and CSA or OSA without excessive daytime sleepiness (EDS), long-term (6-month) ASV therapy yields:
- Beneficial effects on daytime myocardial metabolism leading to a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging;
- Improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index.
Detailed description
DEFINITIONS Obstructive sleep apnea (OSA) is characterized by: episodes of partial or complete pharyngeal collapse leading to obstructive hypopnea and apnea during sleep. OSA often coexists with HF.
Central sleep apnea (CSA) is characterized by: reductions in central respiratory drive during sleep that leads to episodes of partial or complete cessation of airflow. CSA often co-exists with HF.
Continuous positive airway pressure(CPAP) delivers air through a nasal or oral interface to preserve upper airway patency. It is a treatment for symptomatic OSA or some patients with CSA.
Adaptive Servoventilation (ASV) is effective in alleviating OSA and CSA. It provides expiratory positive pressure to alleviate OSA, and inspiratory positive airway pressure to eliminate CSA.
Oxidative metabolism: utilization of substrates via the tricarboxylic acid cycle for Adenosine triphosphate (ATP) production; it is linked to myocardial oxygen consumption and can be measured with [11C]acetate PET.
The work-metabolic index (WMI) is the external work (minute-work) of the left ventricle corrected for the rate of oxidative metabolism and is an estimate of mechanical efficiency.
Myocardial sympathetic neuron (SN) presynaptic function is the measure of uptake and storage of neuronal catecholamines in the heart measured by [11C]hydroxyephedrine (HED) PET.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [C11]Acetate HED PET | Experimental | Other: [C11]Acetate and HED PETAMEND is a single centre substudy of the ADVENT-HF trial. This substudy is a clinical physiologic proposal designed to determine the effects of long-term (6 months) ASV on cardiac energetics and SN function in patients with chronic stable HF and sleep apnea extending our previous evaluation of short-term CPAP in patients with OSA and HF. All subjects consenting to the ADVENT primary trial will be eligible to participate in the substudy. Substudy consenting patients will have [11C]acetate and [11C]HED PET imaging; HR variability; plasma norepinephrine (NE) levels, urine normetanephrine levels within 2 weeks of the sleep study. Baseline measurements will be repeated after 6 months in all patients. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- American Heart Association (AHA) Stages B, C and D heart failure due to ischemic, idiopathic or hypertensive causes with;
- systolic dysfunction, ejection fraction (EF) ≤45% by echocardiography
- optimal medical therapy conforming to the AHA guidelines (and for this proposal, stable therapy for >4 weeks)
- sleep apnea with an Apnea/hypopnea Index ≥15, which will be divided into OSA (> 50% events obstructive), or CSA (> 50% of events central in nature)for patients with OSA, an Epworth Sleepiness Scale score of >10 and no or mild daytime sleepiness (by the International Classification of Sleep Disorders
- age >18 years;
Key exclusion criteria (11 listed)
- Myocardial infarction, cardiac surgery or angioplasty within 3 months prior to enrollment,
- listed for heart transplantation,
- HF due to primary valvular heart disease,
- pregnancy
- current use of ASV or CPAP.
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 |
|---|---|---|
| [C11]Acetate and HED PET | Other | [C11]Acetate HED PET |
Primary outcome
ASV therapy yields a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging in patients with HF, OSA and/or CSA
Time frame: 6 months
ASV therapy yields an improvement in energy transduction from oxidative metabolism to stroke work as measured by an increase in the daytime work-metabolic index inpatients with HF, OSA and/or CSA.
Time frame: 6 months
2 secondary outcomes
ASV for CSA or OSA in patients with HF and sleep apnea will normalize daytime myocardial SN pre-synaptic function measured by [11C]HED retention on PET imaging,
Time frame: 6 months
ASV for CSA or OSA in patients with HF and sleep apnea will normalize daytime sympathetic contributions to heart rate variability
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Background: PubMed 11044422Beanlands RS, Nahmias C, Gordon E, Coates G, deKemp R, Firnau G, Fallen E. The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study. Circulation. 2000 Oct 24;102(17):2070-5. doi: 10.1161/01.cir.102.17.2070.
- Background: PubMed 17258090Yoshinaga K, Burwash IG, Leech JA, Haddad H, Johnson CB, deKemp RA, Garrard L, Chen L, Williams K, DaSilva JN, Beanlands RS. The effects of continuous positive airway pressure on myocardial energetics in patients with heart failure and obstructive sleep apnea. J Am Coll Cardiol. 2007 Jan 30;49(4):450-8. doi: 10.1016/j.jacc.2006.08.059.
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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.
Rob S Beanlands, MD principal investigator
Ottawa Heart Institute Research Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing [C11]Acetate and HED PET in people with Heart Failure and Obstructive Sleep Apnea, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
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 7 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ASV therapy yields a reduction in the rate of oxidative metabolism as measured by [11C]acetate kinetics using PET imaging in patients with HF, OSA and/or CSA (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT02116140, which also lists 2 linked publications.
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 Nov 2025.