Heart Transplant RecipientsAccHeartNCT01759966
Autonomic Cardiovascular Control After Heart Transplantation
An observational study of Heart Transplant Recipients, run by Oslo University Hospital at 1 site in Norway.
Trial summary
The purpose of this prospective study is to investigate denervation (ie. surgical cutting of autonomic nerves) and re-innervation (ie. growth of autonomic nerves) in heart transplant recipients. More specifically, we focus on: 1. Read more about this study
- Who is it for?
- Ages 17 to 69 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Transplant Recipients
- How many people
- 100 participants
- Where
- 1 siteNorway
- Study dates
- Jan 2013to Dec 2019
- Phase
- Observational
- 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 17 to 69 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: This study is to enroll 50 Heart Transplant Recipients (HTRs) and 50 healthy control subjects. HTRs are consecutively invited to participate. Baseline investigations are carried out 7-12 weeks after transplantation surgery. Follow-up investigations are scheduled to 6 months and 1, 2 and 3 years after transplantation Healthy control subjects will be recruited to matcht the distribution of age and gender among HTRs. The will be examined at one time point only; thus, the healthy controls are not subjected to prospective follow-up.
Who may be able to join
- Completed heart transplantation during the last 7-12 weeks
- Age > 16 years and < 70 years
- Age and gender matching the HTRs
Who cannot join
- Peri- or postoperative complications causing permanent dysfunction of the allograft (such as hyperacute rejection episodes, severe myocardial ischemia, etc.)
- Diabetes with HbA1C > 6,5 % and/or manifest diabetic complications
- Renal failure with plasma creatinine > 200 µmol/L
- ECG abnormalities (scattered ectopic beats ad minor conduction problems are allowed)
- Permanently bed-ridden
- Another chronic disease (such as diabetes mellitus)
- Permanent use of pharmaceuticals (including hormone drugs)
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this prospective study is to investigate denervation (ie. surgical cutting of autonomic nerves) and re-innervation (ie. growth of autonomic nerves) in heart transplant recipients. More specifically, we focus on:
- The physiological consequences of denervation, in particular its consequences for clinical symptoms, orthostatic tolerance (ie. the ability to stand upright) and exercise capacity. We hypothesize that denervation has negative consequences for all these factors.
- The pathological consequences of denervation and reinnervation, in particular its association to acute rejection and coronary artery disease (cardiac allograft vasculopathy, CAV). We hypothesize that reinnervation protects against acute rejection and development of CAV
- Donor and recipient factors associated with the reinnervation process. We hypothesize that characteristics of the surgical procedure (such as aorta cross-clamp time) as well as the rehabilitation process of the recipient (such as physical activity) impacts on the reinnervation process.
Read the detailed description
Heart transplantation is annually offered to more than 3500 patients worldwide. In Norway, the number is approximately 30/year, and all transplants are carried out at one single hospital (Oslo University Hospital, Rikshospitalet).
Normally, the heart function is intimately controlled by the autonomic nervous system (ANS), but all nervous connections are lost during the surgical transplantation procedure, and the transplanted heart thus becomes denervated. In time, regrowth of nerves may cause partial reinnervation of the new heart.
Some evidence suggests that reinnervation improves exercise capacity and reduces episodes of acute rejections and the development of cardiac allograft vasculopathy. The purpose of this study is further to investigate the changes over time with respect to all parts of the autonomic nervous system (the sympathetic, parasympathetic and sensoric part), and the associated physiological and pathological consequences.
The study may provide knowledge which ultimately could help us improve health and quality of live for heart transplant recipients.
- Conditions
- Heart Transplant Recipients
- Keywords
- Heart transplantation, Autonomic cardiovascular control, Acute rejection, Cardiac allograft vasculopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Heart transplant recipients | Patients receiving orthotopic heart transplant in the enrollment period | |
| Healthy controls | Healthy control subjects, having the same age and sex distribution as the heart transplant recipients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac allograft vasculopathy
Indications of cardiac allograft vasculopathy (CAV), assessed by intravascular ultrasound (IVUS) during coronary catheterization.
Measured: 1 year
Acute rejections
The frequency of acute rejections episodes and time to first rejection (combined time/event outcome), as assessed by analyses of heart biopsy specimens
Measured: 1 year
Secondary outcomes (13)
Cardiac allograft vasculopathy
Cf. above
Measured: 3 years
Acute rejections
Cf. above
Measured: 2 and 3 years
Autonomic cardiovascular responses
Autonomic cardiovascular responses (such as changes in blood pressures, heart rate, cardiac output, total peripheral resistance and heart rate variability) during head-up tilt-test, valsalva maneuver and isometric exercise
Measured: 6 months, 1, 2 and 3 years
Exercise capacity
Cardio-pulmonary responses to a standardized exercise tolerance test (treadmill), such as maximal oxygen consumption(maxVO2), heart rate increase, blood pressure increase, etc.
Measured: 1, 2 and 3 years
Activity recordings
Number of steps/day during 7 consecutive days, assessed by an accelerometer
Measured: 6 months, 1, 2 and 3 years
Hormonal levels
The levels of catecholamines, cortisol and other hormones influenced by autonomic nervous activity in blood, urine and saliva
Measured: 6 months, 1, 2 and 3 years
General immune activity
The blood levels of cytokines and other markers of immune function, as well as whole blood gene expression.
Measured: 6 months, 1, 2 and 3 years
Pain threshold
Assessment of pain sensitivity by means of an algometer. Anatomically well-defined "trigger-points" are subjected to increasing pressure; the patients alert at the point where the pressure is perceived to be painful
Measured: 6 months, 1, 2 and 3 years
Clinical symptoms
Validated questionnaires assessing: symptoms of autonomic dysfunction, quality of life, pain, fatigue, anxiety, depression and sleep problems.
Measured: 6 months, 1, 2 and 3 years
MetaIodoBenzylGuanidin-scan
The degree of sympathetic cardiac reinnervation as assessed by the scintigraphic method MetaIodoBenzylGuanidin-scan
Measured: 1 and 3 years
Echocardiographic indices
Echocardiographic indices of cardiac function, such as as systolic and diastolic velocities of the ventricular myocardium based on Tissue Doppler Imaging
Measured: 1, 2 and 3 years
Ambulant blood pressure recording
24 hours ambulant blood pressure recordings
Measured: 1, 2 and 3 years
Cardiac catheterization
Routine data from surveillance cardiac catheterization procedures, such as pressure recordings, angiograms and biopsy assessments
Measured: 1, 2 and 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2013 (estimated)
- Study startJan 2013
- Primary completionMar 2016
- Study completionDec 2019 (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 Heart Transplant RecipientsStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- South-Eastern Norway Regional Health Authority
- Responsible party
- Principal investigator, Vegard Bruun Wyller, Oslo University Hospital
- Investigators
- Vegard B Wyller, MD,PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01759966
- Sponsor's protocol ID
- 2012/1428
- Acronym
- AccHeart
- Status last verified
- Apr 2018
- First submitted
- 28 Dec 2012
- Last updated
- 11 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Christensen AH, Nygaard S, Rolid K, Nytroen K, Gullestad L, Fiane A, Thaulow E, Dohlen G, Saul JP, Wyller VBB. Early Signs of Sinoatrial Reinnervation in the Transplanted Heart. Transplantation. 2021 Sep 1;105(9):2086-2096. doi: 10.1097/TP.0000000000003580.
PubMed 33323767
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autonomic Cardiovascular Control After Heart Transplantation
- ClinicalTrials.gov ID
- NCT01759966
- Acronym / sponsor ID
- AccHeart / 2012/1428
- Conditions
- Heart Transplant Recipients
- Keywords
- Heart transplantation, Autonomic cardiovascular control, Acute rejection, Cardiac allograft vasculopathy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- South-Eastern Norway Regional Health Authority
- Study start
- Jan 2013 (actual)
- Primary completion
- Mar 2016 (actual)
- Study completion
- Dec 2019 (estimated)
- First posted
- 3 Jan 2013 (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 purpose of this prospective study is to investigate denervation (ie. surgical cutting of autonomic nerves) and re-innervation (ie. growth of autonomic nerves) in heart transplant recipients. More specifically, we focus on:
- The physiological consequences of denervation, in particular its consequences for clinical symptoms, orthostatic tolerance (ie. the ability to stand upright) and exercise capacity. We hypothesize that denervation has negative consequences for all these factors.
- The pathological consequences of denervation and reinnervation, in particular its association to acute rejection and coronary artery disease (cardiac allograft vasculopathy, CAV). We hypothesize that reinnervation protects against acute rejection and development of CAV
- Donor and recipient factors associated with the reinnervation process. We hypothesize that characteristics of the surgical procedure (such as aorta cross-clamp time) as well as the rehabilitation process of the recipient (such as physical activity) impacts on the reinnervation process.
Detailed description
Heart transplantation is annually offered to more than 3500 patients worldwide. In Norway, the number is approximately 30/year, and all transplants are carried out at one single hospital (Oslo University Hospital, Rikshospitalet).
Normally, the heart function is intimately controlled by the autonomic nervous system (ANS), but all nervous connections are lost during the surgical transplantation procedure, and the transplanted heart thus becomes denervated. In time, regrowth of nerves may cause partial reinnervation of the new heart.
Some evidence suggests that reinnervation improves exercise capacity and reduces episodes of acute rejections and the development of cardiac allograft vasculopathy. The purpose of this study is further to investigate the changes over time with respect to all parts of the autonomic nervous system (the sympathetic, parasympathetic and sensoric part), and the associated physiological and pathological consequences.
The study may provide knowledge which ultimately could help us improve health and quality of live for heart transplant recipients.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Heart transplant recipients | – | –Patients receiving orthotopic heart transplant in the enrollment period |
| Healthy controls | – | –Healthy control subjects, having the same age and sex distribution as the heart transplant recipients |
Who may qualify
- Ages
- 17 to 69 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study is to enroll 50 Heart Transplant Recipients (HTRs) and 50 healthy control subjects. HTRs are consecutively invited to participate. Baseline investigations are carried out 7-12 weeks after transplantation surgery. Follow-up investigations are scheduled to 6 months and 1, 2 and 3 years after transplantation Healthy control subjects will be recruited to matcht the distribution of age and gender among HTRs. The will be examined at one time point only; thus, the healthy controls are not subjected to prospective follow-up.
Key inclusion criteria (3 listed)
- Completed heart transplantation during the last 7-12 weeks
- Age > 16 years and < 70 years
- Age and gender matching the HTRs
Key exclusion criteria (8 listed)
- Peri- or postoperative complications causing permanent dysfunction of the allograft (such as hyperacute rejection episodes, severe myocardial ischemia, etc.)
- Diabetes with HbA1C > 6,5 % and/or manifest diabetic complications
- Renal failure with plasma creatinine > 200 µmol/L
- ECG abnormalities (scattered ectopic beats ad minor conduction problems are allowed)
- Permanently bed-ridden
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cardiac allograft vasculopathy
Time frame: 1 year
Indications of cardiac allograft vasculopathy (CAV), assessed by intravascular ultrasound (IVUS) during coronary catheterization.
Acute rejections
Time frame: 1 year
The frequency of acute rejections episodes and time to first rejection (combined time/event outcome), as assessed by analyses of heart biopsy specimens
13 secondary outcomes
Cardiac allograft vasculopathy
Time frame: 3 years
Acute rejections
Time frame: 2 and 3 years
Autonomic cardiovascular responses
Time frame: 6 months, 1, 2 and 3 years
Exercise capacity
Time frame: 1, 2 and 3 years
Activity recordings
Time frame: 6 months, 1, 2 and 3 years
Hormonal levels
Time frame: 6 months, 1, 2 and 3 years
General immune activity
Time frame: 6 months, 1, 2 and 3 years
Pain threshold
Time frame: 6 months, 1, 2 and 3 years
Clinical symptoms
Time frame: 6 months, 1, 2 and 3 years
MetaIodoBenzylGuanidin-scan
Time frame: 1 and 3 years
Echocardiographic indices
Time frame: 1, 2 and 3 years
Ambulant blood pressure recording
Time frame: 1, 2 and 3 years
Cardiac catheterization
Time frame: 1, 2 and 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2018.
- Derived from this study: PubMed 33323767Christensen AH, Nygaard S, Rolid K, Nytroen K, Gullestad L, Fiane A, Thaulow E, Dohlen G, Saul JP, Wyller VBB. Early Signs of Sinoatrial Reinnervation in the Transplanted Heart. Transplantation. 2021 Sep 1;105(9):2086-2096. doi: 10.1097/TP.0000000000003580.
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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.
Vegard B Wyller, MD,PhD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Transplant Recipients, run by Oslo University Hospital at 1 site in Norway.
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 3 inclusion and 8 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 11 Apr 2018. 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 Norway. 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?
Results are not available in the source record.
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?
Cardiac allograft vasculopathy (time frame: 1 year). 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 NCT01759966, 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 11 Apr 2018.