Clinical trial NCT03399227: Liver Transplantation: Skeletal Effects
Official title: Skeletal Effects of Liver Transplantation
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Liver Diseases
Transplant-Related Disorder
Osteoporosis
Keywords: Bone microarchitecture
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2018-01-16
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 50 patients awaiting liver transplantation and 50 age and gender matched healthy controls

Brief summary: Fifty patients awaiting liver transplantation and 50 age and gender matched control subjects with normal liver function will be included in the study. The aim of this project is to compare liver transplantation recipients'bone microarchitecture with healthy controls and to evaluate patients' changes within one year after transplantation

Detailed description: Background: Solid organ transplantation recipients have a high prevalence of osteoporosis and fragility fractures. Deteriorated bone architecture has been shown by high resolution computed tomography (HR-pQCT) in kidney and lung transplantation recipients. In liver transplantation (LeTx) recipients, bone microarchitecture has only been evaluated using the trabecular bone score in a retrospective cohort study; a degraded or partially degraded microarchitecture was detected in most of the patients.

Aim: The aim of this project is to compare LeTx recipients' bone microarchitecture with healthy controls and to evaluate patients' changes within one year after transplantation.

Methods: HR-pQCT scans of the distal radius and tibia as well as areal bone mineral density measurement of the lumbar spine and hip region will be performed before Tx, 1 and 12 months after Tx in 50 patients. Anabolic and catabolic markers of bone turnover (sclerostin, dickkopf 1, periostin) and traditional bone turnover markers will be evaluated preoperatively, on the day of surgery, and 4 times within the first year after LeTx. In healthy age- and sex-matched controls HR-pQCT, bone mineral density and laboratory parameters will be assessed once.

Hypotheses: Based on the HR-pQCT data of kidney and lung transplantation recipients and the trabecular bone score of LeTx recipients, the investigators hypothesize that LeTX recipients have deteriorated bone microarchitecture.

Expected outcome: Since bone fragility is not only determined by BMD but bone architecture as well, HR-pQCT data give important information on the patients' bone fragility. The knowledge of the course of bone microarchitecture after liver transplantation may help to develop strategies preventing fragility fractures in LeTx recipients.

Eligibility criteria: Inclusion Criteria:

* Women, men awaiting liver Transplantation
* 20-70 years of age

Exclusion Criteria:

* Subjects with a history of prior solid organ transplantation
* Subjects awaiting a combined liver-kidney transplantation
* Cancer within the previous 5 years - except for hepatocellular carcinoma, neuroendocrine tumors and hemangioendothelioma with indication for liver transplantation
* Rheumatoid arthritis
* Severe renal insufficiency (chronic kidney disease IV, V)
* Immobilisation
* Intake of drugs with potential effects on BMD like lithium, estrogen-replacement therapy, selective Estrogen-receptor modulators, oral bisphosphonates in the last three months, denosumab and parenteral bisphosphonates in the last year - except calcium, vitamin D and medication necessary for the underlying disease
* Non-osteoporotic bone disease
* Recent fragility fracture within 6 months

Control group:

Inclusion Criteria:

* Women, men
* 20-70 years of age
* Normal liver function (defined as liver function parameters and transaminases, such as albumin, thromboplastin time, alanine-aminotransferase, aspartate-aminotransferase, and gamma-glutamyl-transferase within the normal range)

Additional exclusion Criteria:

* Osteoporosis according to BMD measurement or osteopenia plus fragility fracture
* Liver disease (defined as evidence of significant liver disease according to laboratory testing)

Primary outcomes:
measure: Bone microarchitecture of the distal radius
timeFrame: 12 months to posttransplantation
Secondary outcomes:
measure: Bone microarchitecture of the distal radius
timeFrame: pretransplantation to 12 after transplantation
measure: Bone microarchitecture of the distal radius
timeFrame: pretransplantation to 12 after transplantation
measure: Bone microarchitecture of the distal radius
timeFrame: pretransplantation to 12 after transplantation
measure: Bone microarchitecture of the distal radius
timeFrame: pretransplantation to 12 after transplantation
measure: Bone microarchitecture of the distal radius
timeFrame: pretransplantation to 12 months after transplantation
Other outcomes:
measure: Bone mineral density
timeFrame: pretransplantation to 12 after transplantation
measure: Bone mineral density
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
measure: Biochemical
timeFrame: pretransplantation to 12 after transplantation
Locations:
Study officials:
affiliation: Medical University of Vienna
name: Katharina Kerschan-Schindl, MD
role: PRINCIPAL_INVESTIGATOR
References: