Autonomic Cardiovascular Control After Heart Transplantation

Heart Transplant Recipients Clinical Trial

— AccHeart  

Official title:

Autonomic Cardiovascular Control After Heart Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01759966
• Other study ID #: 2012/1428
• Status: Active, not recruiting
• First received: December 28, 2012
• Last updated: April 10, 2018
• Start date: January 2013
• Est. completion date: December 2019

Study information

• Verified date: April 2018
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2019
• Est. primary completion date: March 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 17 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Transplant Recipients

Locations

Country	Name	City	State
Norway	Dept. ???of Cardiology, Oslo University Hospital	Oslo

Sponsors (2)

Lead Sponsor	Collaborator
Oslo University Hospital	South-Eastern Norway Regional Health Authority

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac allograft vasculopathy	Indications of cardiac allograft vasculopathy (CAV), assessed by intravascular ultrasound (IVUS) during coronary catheterization.	1 year
Primary	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	1 year
Secondary	Cardiac allograft vasculopathy	Cf. above	3 years
Secondary	Acute rejections	Cf. above	2 and 3 years
Secondary	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	6 months, 1, 2 and 3 years
Secondary	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.	1, 2 and 3 years
Secondary	Activity recordings	Number of steps/day during 7 consecutive days, assessed by an accelerometer	6 months, 1, 2 and 3 years
Secondary	Hormonal levels	The levels of catecholamines, cortisol and other hormones influenced by autonomic nervous activity in blood, urine and saliva	6 months, 1, 2 and 3 years
Secondary	General immune activity	The blood levels of cytokines and other markers of immune function, as well as whole blood gene expression.	6 months, 1, 2 and 3 years
Secondary	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	6 months, 1, 2 and 3 years
Secondary	Clinical symptoms	Validated questionnaires assessing: symptoms of autonomic dysfunction, quality of life, pain, fatigue, anxiety, depression and sleep problems.	6 months, 1, 2 and 3 years
Secondary	MetaIodoBenzylGuanidin-scan	The degree of sympathetic cardiac reinnervation as assessed by the scintigraphic method MetaIodoBenzylGuanidin-scan	1 and 3 years
Secondary	Echocardiographic indices	Echocardiographic indices of cardiac function, such as as systolic and diastolic velocities of the ventricular myocardium based on Tissue Doppler Imaging	1, 2 and 3 years
Secondary	Ambulant blood pressure recording	24 hours ambulant blood pressure recordings	1, 2 and 3 years
Secondary	Cardiac catheterization	Routine data from surveillance cardiac catheterization procedures, such as pressure recordings, angiograms and biopsy assessments	1, 2 and 3 years