Investigation of Pain Incidence After FK506 Immunosuppressive Therapy in Liver Transplantation Patients

Study Overview
=================
Brief Summary
-----------------
FK506 (tacrolimus), a calcineurin inhibitor, is widely used as an immunosuppressant to lower the risk of organ rejection after organ transplantation, and to treat T cell-mediated diseases such as eczema and atopic dermatitis. FK506 treatment often accompanies pain sensation in patients with atopic dermatitis or after organ transplantation. In previous studies, we confirmed that FK506 treatment increased neuronal activity of primary afferent neurons and causes pain behavior in naïve mice. In order to further search for objective clinical evidence, we proposed to investigate pain incidence after FK506 immunosuppressive therapy in liver transplantation patients. We will investigate pain incidence and pain intensity in patients who underwent liver transplant from September of 2011 to May of 2018 in the Liver Health Rehabilitation Association. The patients who were divided into two groups based on whether or not FK506 was used in the immunosuppressive therapy. The patients in control group (without FK506 treatment) and FK506-treated group report pain sensation 3 months and 12 months after liver transplant. We will compare the pain incidence between the two groups at both time points. On the other hand, we will further investigate changes in pain sensation after 1st and 2nd reductions of FK506 dose. Pain is reported subjectively by the patient using the visual analogue scale (VAS) 1 month after dose reduction. In our study, 1st and 2nd reductions of FK506 dose refers to the first two dose-adjustments (approximately 6 months apart) that occurred 3-6 months after the liver transplantation.

Official Title
-----------------
Investigation of Pain Incidence After FK506 Immunosuppressive Therapy in Liver Transplantation Patients

Conditions
-----------------
Chronic Pain, Liver Transplantation

Intervention / Treatment
-----------------
* Drug: FK506


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: had liver transplantation for end-stage liver disease was ≥18 years of age at the time of liver transplantation - Exclusion Criteria: liver cancer acute (fulminant) liver failure multiorgan transplant chronic postsurgical pain fibromyalgia, osteoarthritis, low back pain and inflammatory pain of any origin peripheral and central neuropathic pain of any origin chronic secondary visceral pain chronic cancer-related pain that is due to cancer or its treatment -

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| FK506-treated group<br>In FK506-treated group, the patients who underwent liver transplant are treated with FK506 immunosuppressive therapy. | Drug: FK506<br>* FK506 (tacrolimus), a calcineurin inhibitor, is widely used as an immunosuppressant to lower the risk of organ rejection after organ transplantation<br>|
| control group without FK506 treatment<br>In control group, the patients who underwent liver transplant are treated without FK506. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pain incidence | Pain is defined as painful sensation that lasts or recurs for 1-3 months within 3 months after liver transplantation, or for longer than 3 months within 12 months after liver transplantation. | within 2 years after liver transplantation | 
| pain intensity | Pain is reported subjectively by the patient using the visual analogue scale (VAS) | within 2 years after liver transplantation | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Pain, Liver Transplantation, FK506