Autonomic Cardiovascular Control After Heart Transplantation

NCT01759966 | Unknown

• 1 other identifier: 2012/1428
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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. 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.

Conditions

Heart Transplant Recipients

Keywords

Heart transplantation; Autonomic cardiovascular control; Acute rejection; Cardiac allograft vasculopathy

Outcome Measures

Primary Outcomes (2)

• Cardiac allograft vasculopathy

  Indications of cardiac allograft vasculopathy (CAV), assessed by intravascular ultrasound (IVUS) during coronary catheterization.

  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

  1 year

Secondary Outcomes (13)

• Cardiac allograft vasculopathy

  3 years

• Acute rejections

  2 and 3 years

• Autonomic cardiovascular responses

  6 months, 1, 2 and 3 years

• Exercise capacity

  1, 2 and 3 years

• Activity recordings

  6 months, 1, 2 and 3 years

Study Arms (2)

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

Eligibility Criteria

• Age: 17 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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
• \- Age and gender matching the HTRs
• Another chronic disease (such as diabetes mellitus)
• Permanent use of pharmaceuticals (including hormone drugs)
• Pregnancy

Sponsors & Collaborators

• Oslo University Hospital: lead
• South-Eastern Norway Regional Health Authority: collaborator

Study Sites (1)

Dept. of Cardiology, Oslo University Hospital

Oslo, N-0027, Norway

Location

Related Publications (1)

• 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.

  PMID: 33323767 DERIVED

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)

Study Officials

• Vegard B Wyller, MD,PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD Dept of Pediatrics, Oslo University Hospital, Norway

Study Record Dates

• First Submitted: December 28, 2012
• First Posted: January 3, 2013
• Study Start: January 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: December 1, 2019
• Last Updated: April 11, 2018

Record last verified: 2018-04

Locations

NO (1)