Sertraline Effect in Uremic Pruritis

Study Overview
=================
Brief Summary
-----------------
This study aims to assess the effect of sertraline on uremic pruritis in patients undergoing regular haemodialysis.

Detailed Description
-----------------
The reported prevalence of uremic pruritus in adult hemodialysis patients has varied over the years, and some studies suggest the prevalence may be decreasing with more effective dialysis. One of the largest trials (the Dialysis Outcomes and Practice Patterns Study [DOPPS]) reported that the prevalence of moderate pruritus remained constant at 18 percent until 2015. A direct role for proinflammatory T cells and cytokines is suggested by studies that showed higher levels of proinflammatory T helper-1 (TH1) cells, C-reactive protein, interleukin-6, and interleukin-2 levels among hemodialysis patients versus those without pruritus. Also, histamine release from mast cells, other pruritogens and xerosis have been all implicated in the pathogenesis of uremic pruritus. Less convincing associations have also been made to anemia, male sex, increased beta-2 microglobulin levels, serotype human leukocyte antigen (HLA)-B35, and comorbidities including congestive heart failure and neurologic disease. The risk of uremic pruritis appears to be independent of ethnicity, type of dialysis, and underlying renal disease. No single cause underlying uremic pruritus has been identified. Multiple factors have been associated in observational studies, and supportive therapies that are used to treat uremic pruritus have targeted such factors. High quality evidence on which to base recommendations for the treatment of uremic pruritus is limited. Many pharmacologic treatments have been proposed for uremic pruritis through different clinical trials. However, the results were quite variable and most of these studies were small uncontrolled trials and hence they were flawed. Several studies have revealed that the selective serotonin reuptake inhibitors (SSRI) could reduce the severity of pruritus. Sertraline hydrochloride is a selective serotonin reuptake inhibitor which established improvement in itching in patients with cholestatic pruritis. This was supported by Browning et al. (2003) whose study showed 86% of subjects who had been given sertraline for another indication improved considerably with pruritus disappearing in 30% of the subjects. Generally, most of the previous research has tended to focus on cholestatic pruritis rather than uremic pruritis. Although enough is known to determine a reasonable approach to a patient with uremic pruritus, more research is needed to understand the pathophysiology of this condition and to establish more reliable treatments. Hence, this study is organized in an attempt to find out the effect of sertraline on alleviation of uremic pruritus.

Official Title
-----------------
Effectiveness of Sertraline in Alleviating Uremic Pruritis in Hemodialysis Patients

Conditions
-----------------
Uremic Pruritis

Intervention / Treatment
-----------------
* Drug: sertraline
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ≥1 month of maintenance haemodialysis, 3 times per week for 4 hours. Adult patients with ages between 18-80 years. Exclusion Criteria: Primary skin diseases (eczema, psoriasis, allergic dermatitis or drug rash). Peripheral neuropathy, thyroid disease, leukemia, lymphoma, liver disease, Systemic lupus erythematosus or pregnancy. Patients who consumed emollients cream, antihistamine, opioid antagonist, immunosuppressants, cholestyramine, corticosteroids or UVB phototherapy 1 month before study. calcium X phosphorus (Ca X P) >55.0 mg/dl, P >5.5 mg/dl, parathyroid hormone (PTH) >450 pg/ml. Selective serotonin reuptake inhibitors intolerance.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This research is a double-blinded randomized multicentric clinical trial in which 50 haemodialysis patients will be randomly assigned to one of the study groups using block randomization with a ratio of 1:1. Group A: 25 patients will receive sertraline at the intended dose of 50 mg twice daily for 8 weeks. Group B: 25 patients will receive a placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sertraline<br>they will receive sertraline at the intended dose of 50 mg twice daily for 8 weeks. | Drug: sertraline<br>* sertraline at the intended dose of 50 mg twice daily for 8 weeks.<br>|
| Placebo Comparator: placebo<br>They will receive a placebo in the form of multivitamin tablets similar to the experimental drug with the same regimen, as one tablet /day for 8 weeks | Drug: placebo<br>* a placebo in the form of multivitamin tablets similar to the experimental drugs with the same regimen (one tablet /day for 8 weeks)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in uremic pruritis intensity | Assessment of pruritis will be done before and after the course of treatment (8 weeks) through the following scores: I) Visual analogue scale (VAS) II) 5D itch scale | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
sertraline, hemodialysis