Clinical trial NCT05994274: A Clinical Study of Association Between Postoperative Dyslipidemia and Organ Rejection in Transplant Patients
Official title: A Prospective Clinical Study of Association Between Postoperative Dyslipidemia and Organ
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Transplant Failure and Rejection
Keywords: heart transplantation
Macrophages
Fatty acid
PCSK9
Lipid metabolism
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2023-08-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients who have undergone heart transplant.

Brief summary: Abnormal lipid metabolism is a common complication after organ transplantation, with pathological changes in lipid parameters occurring in approximately 60-80% of cardiac transplant recipients receiving triple immunotherapy with cyclosporine, imid azathioprine, and methylprednisolone. With the significant increase in long-term survival and increasing age of transplant patients, atherosclerotic cardiovascular diseases, such as those caused by dyslipidemia, have become a major cause of transplant organ failure and recipient death. However, the causes of dyslipidemia after organ transplantation, as well as the effects and mechanisms of dyslipidemia on transplant rejection, are unknown.

Previous studies have found that 1. increased lipid levels occur in recipients after heart transplantation; 2. during rejection, hepatic PCSK9 expression is increased in recipients; 3. a high-fat environment increases the immunoreactivity of human peripheral blood lymphocytes. It is suggested that PCSK9-lipid disorder-immune cell interactions may be associated with the development of transplant rejection.

In this project, we propose to (1) establish a long-term follow-up system for postoperative cardiac transplantation patients in our department to track the characteristics of lipid changes in transplantation patients, to clarify the link between dyslipidemia and rejection, and to provide a strong evidence-based medical basis for the management of lipids during the perioperative period and in the postoperative period; (2) expand the dimensions of lipid-related assays under the support of the above system, and to incorporate transcriptomic, proteomic, and metabolomic research methods to elucidate transplantation rejection in a multidimensional manner. (ii) Expanding the dimensions of lipid-related assays to include transcriptomic, proteomic, and metabolomic studies to elucidate the relationship between PCSK9 and dyslipidemia in transplant patients; (iii) Adopting single-cell sequencing technology to deeply reveal the potential mechanism by which changes in lipids affect T-cell-mediated rejection of cardiac transplants. The mechanism of T-cell-mediated cardiac transplantation rejection is revealed by single-cell sequencing.


Eligibility criteria: Inclusion Criteria:

* After heart transplantation
* Age ≥ 18
* Disease duration: symptomatic heart failure ≥ 6 months prior to screening date
* The patient's informed consent

Exclusion Criteria:

* Refusal of the patient to provide consent
* Suspected poor capability to follow instructions and cooperate
* Another life-threatening disease with poor prognosis (survival less than 2 years)
* Participation in any other clinical study within less than 30 days prior to screening date

Primary outcomes:
measure: Blood lipid measurements
timeFrame: 4 years
measure: Graft/Patient survival
timeFrame: 4 years
Secondary outcomes:
measure: Left ventricular ejection fraction (LVEF) at rest
timeFrame: 4 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan Union Hospital
Study officials:
References: