Cardiac Resynchronization TherapyEarly Phase 1NCT02258061
Optimal Cardiac Resynchronization Therapy Pacing Rate
A Early Phase 1 study testing DDD-80 and DDD-60 in people with Cardiac Resynchronization Therapy and Heart Failure, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
The optimal pacing rate during cardiac resynchronization therapy (CRT) is not known. Investigators investigate the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Resynchronization Therapy, Heart Failure, Bi-ventricular Pacing
- What is being tested?
- DDD-80 and DDD-60
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2011to Jun 2013
- Phase
- Early 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis with idiopathic dilated cardiomyopathy
- CRT device implanted (with initial indication in accordance with European guidelines) at least 6 months prior to inclusion.
- New York Heart Association functional (NYHA) class II-IV
- Sinus rhythm,
- Hemodynamically stable
- Biventricular pacing > 90% of the time
- On optimal medical treatment for heart failure with no changes in medications during the past 3 months.
Who cannot join
- NYHA I
- unable to perform exercise test (e.g. chronic obstructive pulmonary disease, severe arthritis)
- cancer
- plasma creatinine > 200 micromole per litre
- an admission for decompensated HF or acute coronary syndrome in the preceding 3 months.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Rigshospitalet, University hospital of Copenhagen
Copenhagen, 2100
About this study
Official title: Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-ischemic Heart Failure Patients: a Randomized Crossover Pilot Trial.
The optimal pacing rate during cardiac resynchronization therapy (CRT) is not known. Investigators investigate the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).
Read the detailed description
This is a double-blinded randomized crossover pilot study testing two basal pacing rates: DDD-60 versus DDD-80. Each patient is paced for 2 periods of 90 days with DDD-60 and DDD-80 in a randomly sequence.
Blood samples NT-proBNP plasma levels are analysed at baseline and at the end of each phase using electrochemiluminescence-immunoassay. Patients rest for 15 minutes before the samples are taken.
These result are monitored by supervisory group to ensure that increase of more than 15% than baseline values result in termination of study.
Investigators conduct two distinct questionnaires (Minnesota Living with Heart Failure (LIfHE) questionnaire and Medical Outcome Survey Short Form (SF-36)) A symptom limiting bicycle (Ergoline, Baden-Württemberg, Germany) exercise test is performed to measure maximum work capacity and oxygen consumption at each phase.
Recordings of resting muscle sympathetic nerve activity (MSNA) are sought in all patients at both rates of pacing. All patients are studied on the same set-up in the semi-recumbent position after 30 minutes of rest. Tungsten microelectrodes (Iowa Bioengineering) are inserted into the common peroneal nerve just below the knee.
- Conditions
- Cardiac Resynchronization Therapy, Heart Failure, Bi-ventricular Pacing, Sympathetic Activity, Quality of Life
- Being tested
- DDD-80, DDD-60
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DDD-80Procedure or surgery
Basal pacing rate set to 80-bpm. Note:Patients have already pacemaker implanted before this study.
DDD-60Procedure or surgery
Basal pacing rate set to 60-bpm. Note:Patients have already pacemaker implanted before this study.
| Study group | Role | What they receive |
|---|---|---|
| DDD-80 pacing | Experimental | To investigate the impact of basal pacing rates of 80-bpm (DDD-80) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) and (iii) self-perceived quality of life (QoL). Receives: Procedure: DDD-80 |
| DDD-60 pacing | Sham comparator | To investigate the impact of basal pacing rates of 60-bpm (DDD-60) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) self-perceived quality of life (QoL). Receives: Procedure: DDD-60 |
What is being measured
The primary outcome is the main question the study is designed to answer.
N-terminal pro-brain natriuretic peptide
Observing the change in N-terminal pro-brain natriuretic peptide in 15 patients
Measured: 3 months
Secondary outcomes (3)
Autonomic nerve function
Autonomic nerve function by micro-neurography measured in bursts/min and bursts/cardiac cycle in 15 patients
Measured: 3 months
Peak oxygen consumption (pVO2)
pVO2 measured by a symptom limiting bicycle exercise test in 15 patients
Measured: 3 months
Self-perceived quality of life
Measured with the LIfHE and SF-36 questionnaires in 15 patients
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2014 (estimated)
- Study startAug 2011
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Cardiac Resynchronization TherapyStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Adam Ali Ghotbi, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Adam A Ghotbi, MD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02258061
- Sponsor's protocol ID
- H-3-2011-034
- Status last verified
- Oct 2014
- First submitted
- 29 Sep 2014
- Last updated
- 7 Oct 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kuniyoshi RR, Martinelli M, Negrao CE, Siqueira SF, Rondon MU, Trombetta IC, Kuniyoshi FH, Laterza MC, Nishioka SA, Costa R, Tamaki WT, Crevelari ES, Peixoto Gde L, Ramires JA, Kalil R. Effects of cardiac resynchronization therapy on muscle sympathetic nerve activity. Pacing Clin Electrophysiol. 2014 Jan;37(1):11-8. doi: 10.1111/pace.12254. Epub 2013 Aug 16.
PubMed 23952584Agostoni P, Corra U, Cattadori G, Veglia F, Battaia E, La Gioia R, Scardovi AB, Emdin M, Metra M, Sinagra G, Limongelli G, Raimondo R, Re F, Guazzi M, Belardinelli R, Parati G, Magri D, Fiorentini C, Cicoira M, Salvioni E, Giovannardi M, Mezzani A, Scrutinio D, Di Lenarda A, Mantegazza V, Ricci R, Apostolo A, Iorio A, Paolillo S, Palermo P, Contini M, Vassanelli C, Passino C, Piepoli MF; MECKI Score Research Group. Prognostic value of indeterminable anaerobic threshold in heart failure. Circ Heart Fail. 2013 Sep 1;6(5):977-87. doi: 10.1161/CIRCHEARTFAILURE.113.000471. Epub 2013 Jul 23.
PubMed 23881847Stockburger M, de Teresa E, Lamas G, Desaga M, Koenig C, Habedank D, Cobo E, Navarro X, Wiegand U. Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy. Europace. 2014 Jan;16(1):63-70. doi: 10.1093/europace/eut217. Epub 2013 Jul 16.
PubMed 23861381Brenyo A, Barsheshet A, Rao M, Huang DT, Zareba W, McNitt S, Hall WJ, Peterson DR, Solomon SD, Moss AJ, Goldenberg I. Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure. Circ Heart Fail. 2013 Sep 1;6(5):998-1004. doi: 10.1161/CIRCHEARTFAILURE.112.000174. Epub 2013 Jun 25.
PubMed 23801020Shukla A, Curtis AB, Mehra MR, Albert NM, Gheorghiade M, Heywood JT, Liu Y, O'Connor CM, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Factors associated with improvement in utilization of cardiac resynchronization therapy in eligible heart failure patients: findings from IMPROVE HF. Pacing Clin Electrophysiol. 2013 Apr;36(4):433-43. doi: 10.1111/pace.12090. Epub 2013 Feb 4.
PubMed 23380000Martin DO, Day JD, Lai PY, Murphy AL, Nayak HM, Villareal RP, Weiner S, Kraus SM, Stolen KQ, Gold MR. Atrial support pacing in heart failure: results from the multicenter PEGASUS CRT trial. J Cardiovasc Electrophysiol. 2012 Dec;23(12):1317-25. doi: 10.1111/j.1540-8167.2012.02402.x. Epub 2012 Jul 25.
PubMed 22830441Ghotbi AA, Sander M, Kober L, Philbert BT, Gustafsson F, Hagemann C, Kjaer A, Jacobsen PK. Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial. PLoS One. 2015 Sep 18;10(9):e0138124. doi: 10.1371/journal.pone.0138124. eCollection 2015.
PubMed 26382243
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-ischemic Heart Failure Patients: a Randomized Crossover Pilot Trial.
- ClinicalTrials.gov ID
- NCT02258061
- Acronym / sponsor ID
- H-3-2011-034
- Conditions
- Cardiac Resynchronization Therapy, Heart Failure, Bi-ventricular Pacing, Sympathetic Activity, Quality of Life
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 7 Oct 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.
The optimal pacing rate during cardiac resynchronization therapy (CRT) is not known. Investigators investigate the impact of changing basal pacing frequencies on autonomic nerve function, cardiopulmonary exercise capacity and self-perceived quality of life (QoL).
Detailed description
This is a double-blinded randomized crossover pilot study testing two basal pacing rates: DDD-60 versus DDD-80. Each patient is paced for 2 periods of 90 days with DDD-60 and DDD-80 in a randomly sequence.
Blood samples NT-proBNP plasma levels are analysed at baseline and at the end of each phase using electrochemiluminescence-immunoassay. Patients rest for 15 minutes before the samples are taken.
These result are monitored by supervisory group to ensure that increase of more than 15% than baseline values result in termination of study.
Investigators conduct two distinct questionnaires (Minnesota Living with Heart Failure (LIfHE) questionnaire and Medical Outcome Survey Short Form (SF-36)) A symptom limiting bicycle (Ergoline, Baden-Württemberg, Germany) exercise test is performed to measure maximum work capacity and oxygen consumption at each phase.
Recordings of resting muscle sympathetic nerve activity (MSNA) are sought in all patients at both rates of pacing. All patients are studied on the same set-up in the semi-recumbent position after 30 minutes of rest. Tungsten microelectrodes (Iowa Bioengineering) are inserted into the common peroneal nerve just below the knee.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DDD-80 pacing | Experimental | Procedure: DDD-80To investigate the impact of basal pacing rates of 80-bpm (DDD-80) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) and (iii) self-perceived quality of life (QoL). |
| DDD-60 pacing | Sham comparator | Procedure: DDD-60To investigate the impact of basal pacing rates of 60-bpm (DDD-60) in CRT patients on: (i) autonomic nerve function; assessed by micro-neurography, and N-terminal pro-brain natriuretic peptide (NT-proBNP) and (ii) peak oxygen consumption (pVO2) self-perceived quality of life (QoL). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis with idiopathic dilated cardiomyopathy
- CRT device implanted (with initial indication in accordance with European guidelines) at least 6 months prior to inclusion.
- New York Heart Association functional (NYHA) class II-IV
- Sinus rhythm,
- Hemodynamically stable
Key exclusion criteria (5 listed)
- NYHA I
- unable to perform exercise test (e.g. chronic obstructive pulmonary disease, severe arthritis)
- cancer
- plasma creatinine > 200 micromole per litre
- an admission for decompensated HF or acute coronary syndrome in the preceding 3 months.
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 |
|---|---|---|
| DDD-80Basal pacing rate set to 80-bpm. Note:Patients have already pacemaker implanted before this study. | Procedure or surgery | DDD-80 pacing |
| DDD-60Basal pacing rate set to 60-bpm. Note:Patients have already pacemaker implanted before this study. | Procedure or surgery | DDD-60 pacing |
Primary outcome
N-terminal pro-brain natriuretic peptide
Time frame: 3 months
Observing the change in N-terminal pro-brain natriuretic peptide in 15 patients
3 secondary outcomes
Autonomic nerve function
Time frame: 3 months
Peak oxygen consumption (pVO2)
Time frame: 3 months
Self-perceived quality of life
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2014.
- Background: PubMed 23952584Kuniyoshi RR, Martinelli M, Negrao CE, Siqueira SF, Rondon MU, Trombetta IC, Kuniyoshi FH, Laterza MC, Nishioka SA, Costa R, Tamaki WT, Crevelari ES, Peixoto Gde L, Ramires JA, Kalil R. Effects of cardiac resynchronization therapy on muscle sympathetic nerve activity. Pacing Clin Electrophysiol. 2014 Jan;37(1):11-8. doi: 10.1111/pace.12254. Epub 2013 Aug 16.
- Background: PubMed 23881847Agostoni P, Corra U, Cattadori G, Veglia F, Battaia E, La Gioia R, Scardovi AB, Emdin M, Metra M, Sinagra G, Limongelli G, Raimondo R, Re F, Guazzi M, Belardinelli R, Parati G, Magri D, Fiorentini C, Cicoira M, Salvioni E, Giovannardi M, Mezzani A, Scrutinio D, Di Lenarda A, Mantegazza V, Ricci R, Apostolo A, Iorio A, Paolillo S, Palermo P, Contini M, Vassanelli C, Passino C, Piepoli MF; MECKI Score Research Group. Prognostic value of indeterminable anaerobic threshold in heart failure. Circ Heart Fail. 2013 Sep 1;6(5):977-87. doi: 10.1161/CIRCHEARTFAILURE.113.000471. Epub 2013 Jul 23.
- Background: PubMed 23861381Stockburger M, de Teresa E, Lamas G, Desaga M, Koenig C, Habedank D, Cobo E, Navarro X, Wiegand U. Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy. Europace. 2014 Jan;16(1):63-70. doi: 10.1093/europace/eut217. Epub 2013 Jul 16.
- Background: PubMed 23801020Brenyo A, Barsheshet A, Rao M, Huang DT, Zareba W, McNitt S, Hall WJ, Peterson DR, Solomon SD, Moss AJ, Goldenberg I. Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure. Circ Heart Fail. 2013 Sep 1;6(5):998-1004. doi: 10.1161/CIRCHEARTFAILURE.112.000174. Epub 2013 Jun 25.
- Background: PubMed 23380000Shukla A, Curtis AB, Mehra MR, Albert NM, Gheorghiade M, Heywood JT, Liu Y, O'Connor CM, Reynolds D, Walsh MN, Yancy CW, Fonarow GC. Factors associated with improvement in utilization of cardiac resynchronization therapy in eligible heart failure patients: findings from IMPROVE HF. Pacing Clin Electrophysiol. 2013 Apr;36(4):433-43. doi: 10.1111/pace.12090. Epub 2013 Feb 4.
- Background: PubMed 22830441Martin DO, Day JD, Lai PY, Murphy AL, Nayak HM, Villareal RP, Weiner S, Kraus SM, Stolen KQ, Gold MR. Atrial support pacing in heart failure: results from the multicenter PEGASUS CRT trial. J Cardiovasc Electrophysiol. 2012 Dec;23(12):1317-25. doi: 10.1111/j.1540-8167.2012.02402.x. Epub 2012 Jul 25.
- Derived from this study: PubMed 26382243Ghotbi AA, Sander M, Kober L, Philbert BT, Gustafsson F, Hagemann C, Kjaer A, Jacobsen PK. Optimal Cardiac Resynchronization Therapy Pacing Rate in Non-Ischemic Heart Failure Patients: A Randomized Crossover Pilot Trial. PLoS One. 2015 Sep 18;10(9):e0138124. doi: 10.1371/journal.pone.0138124. eCollection 2015.
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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.
Adam A Ghotbi, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing DDD-80 and DDD-60 in people with Cardiac Resynchronization Therapy and Heart Failure, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 5 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: finished, as of the sponsor's last update on 7 Oct 2014. 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 Denmark. 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. Some participants in this study may receive a placebo. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
N-terminal pro-brain natriuretic peptide (time frame: 3 months). 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 NCT02258061, which also lists 7 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 7 Oct 2014.