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Autonomic Cardiovascular Control After Heart Transplantation (AccHeart)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Oslo University Hospital
Sponsor:
Collaborator:
South-Eastern Norway Regional Health Authority
Information provided by (Responsible Party):
Vegard Bruun Wyller, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT01759966
First received: December 28, 2012
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

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. 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.
  2. 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
  3. 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.

Condition
Heart Transplant Recipients

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Autonomic Cardiovascular Control After Heart Transplantation

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • Cardiac allograft vasculopathy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Indications of cardiac allograft vasculopathy (CAV), assessed by intravascular ultrasound (IVUS) during coronary catheterization.

  • Acute rejections [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The frequency of acute rejections episodes and time to first rejection (combined time/event outcome), as assessed by analyses of heart biopsy specimens


Secondary Outcome Measures:
  • Cardiac allograft vasculopathy [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Cf. above

  • Acute rejections [ Time Frame: 2 and 3 years ] [ Designated as safety issue: No ]
    Cf. above

  • Autonomic cardiovascular responses [ Time Frame: 6 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    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

  • Exercise capacity [ Time Frame: 1, 2 and 3 years ] [ Designated as safety issue: No ]
    Cardio-pulmonary responses to a standardized exercise tolerance test (treadmill), such as maximal oxygen consumption(maxVO2), heart rate increase, blood pressure increase, etc.

  • Activity recordings [ Time Frame: 6 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    Number of steps/day during 7 consecutive days, assessed by an accelerometer

  • Hormonal levels [ Time Frame: 6 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    The levels of catecholamines, cortisol and other hormones influenced by autonomic nervous activity in blood, urine and saliva

  • General immune activity [ Time Frame: 6 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    The blood levels of cytokines and other markers of immune function, as well as whole blood gene expression.

  • Pain threshold [ Time Frame: 6 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    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

  • Clinical symptoms [ Time Frame: 6 months, 1, 2 and 3 years ] [ Designated as safety issue: No ]
    Validated questionnaires assessing: symptoms of autonomic dysfunction, quality of life, pain, fatigue, anxiety, depression and sleep problems.

  • MetaIodoBenzylGuanidin-scan [ Time Frame: 1 and 3 years ] [ Designated as safety issue: No ]
    The degree of sympathetic cardiac reinnervation as assessed by the scintigraphic method MetaIodoBenzylGuanidin-scan

  • Echocardiographic indices [ Time Frame: 1, 2 and 3 years ] [ Designated as safety issue: No ]
    Echocardiographic indices of cardiac function, such as as systolic and diastolic velocities of the ventricular myocardium based on Tissue Doppler Imaging

  • Ambulant blood pressure recording [ Time Frame: 1, 2 and 3 years ] [ Designated as safety issue: No ]
    24 hours ambulant blood pressure recordings

  • Cardiac catheterization [ Time Frame: 1, 2 and 3 years ] [ Designated as safety issue: No ]
    Routine data from surveillance cardiac catheterization procedures, such as pressure recordings, angiograms and biopsy assessments


Biospecimen Retention:   Samples With DNA
  1. Blood samples for analyses of: genomic DNA, RNA-transcription in whole blood, cytokines, cathecholamines, other blood biomarkers
  2. Urine samples for analyses of: catecholamines, cortisol, other urine biomarkers
  3. Saliva samples for analyses of: cortisol
  4. Heart biopsy specimen for analyses of: acute and chronic rejection (routine surveillence procedure)

Estimated Enrollment: 100
Study Start Date: January 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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.

  Eligibility

Ages Eligible for Study:   17 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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.

Criteria

Inclusion Criteria HTRs:

  • Completed heart transplantation during the last 7-12 weeks
  • Age > 16 years and < 70 years

Exclusion criteria HTRs:

  • 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

Inclusion criteria healthy controls:

- Age and gender matching the HTRs

Exclusion criteria healthy controls:

  • Another chronic disease (such as diabetes mellitus)
  • Permanent use of pharmaceuticals (including hormone drugs)
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01759966

Contacts
Contact: Sissel I Nygaard, MD +47 23070000 UXSIYG@ous-hf.no
Contact: Vegard B Wyller, MD, PhD brwylle@online.no

Locations
Norway
Dept. of Cardiology, Oslo University Hospital Recruiting
Oslo, Norway, N-0027
Contact: Sissel I Nygaard, MD    +47 23070000    UXSIYG@ous-hf.no   
Contact: Vegard B Wyller, MD,PhD       brwylle@online.no   
Principal Investigator: Vegard B Wyller, MD,PhD         
Sponsors and Collaborators
Oslo University Hospital
South-Eastern Norway Regional Health Authority
Investigators
Principal Investigator: Vegard B Wyller, MD,PhD Oslo University Hospital
  More Information

No publications provided

Responsible Party: Vegard Bruun Wyller, MD, PhD Dept of Pediatrics, Oslo University Hospital, Norway, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT01759966     History of Changes
Other Study ID Numbers: 2012/1428
Study First Received: December 28, 2012
Last Updated: January 18, 2013
Health Authority: Norway: Regional Ethics Commitee
Norway: Data Protection Authority

Keywords provided by Oslo University Hospital:
Heart transplantation
Autonomic cardiovascular control
Acute rejection
Cardiac allograft vasculopathy

ClinicalTrials.gov processed this record on September 16, 2014