Treatment of Chronic Itch in Patients Under Arsenic Exposure With Sublingual Naloxone: A Double-blind Randomized Controlled Trial
Phase: PHASE1
Conditions: Chronic Pruritus
Sponsor: Xiangya Hospital of Central South University

Study Protocol and Statistical Analysis Plan 
 
Treatment of Chronic Itch in Patients Under Arsenic Exposure With Sublingual Naloxone: A Double-
blind Randomized Controlled Trial 
 
NCT number: 2018/NAL/CSU/PRU 
Date: 2020.10.1 
 
Study design 
To test whether the inhibition of β-endorphin (μ-opioid) receptor alleviates itch in patients under chronic 
arsenic exposure, we conducted a randomized, double-blind, placebo-controlled trial. We randomly assigned 
patients to naloxone (0.4 mg/qd, sublingual) and placebo (0.4 mg/qd, sublingual) using a computer-generated 
sequence of random numbers during January 2019 to March 2019. The trial consisted of a one-week 
treatment period and a one-week withdrawl period. The primary outcome (severity of itch) was evaluated 
using the NRS through a face-to-face interview on baseline (Day 0) and the last day of the treatment period 
(Day 7), and a telephone interview on the last day of the withdrawl period (Day 14). The participants were 
also inquired about the possible adverse events of naloxone such as headache, sleep difficulty, sickness, and 
dizziness in each interview. 
 
Inclusion and exclusion criteria 
The inclusion criteria include: the participants must be above 18 years, be able to understand the study 
protocol and sign informed consent voluntarily, and report moderate-to-severe itch (NRS≥3). Participants 
were excluded if they used anti-histamines, anti- inflammatory, anti-pruritic, analgesic, antidepressant, or 
anti-epileptic agents within 2 weeks prior to the study, or had a history of pruritic skin diseases such as 
eczema and psoriasis. 
 
Statistical analysis 
In the randomized controlled trial, an intention-to-treat (ITT) analysis was performed to evaluate the efficacy of 
naloxone. The last observation carry-forward (LOCF) imputation method was used for unmeasured data in 
drop-out participants. Mixed effect models were used to estimate the efficacy, by constructing a model: Y 
= β0 + β1Group + β2Time + β3(Group×Time) + ei + υij, where β3 is the estimate for efficacy; ei and υij refer to 
the errors between individuals and within an individual (repeated measurements), respectively. Statistical 
analyses were performed in R Statistical Software 3.4.1. The significance level for all statistical tests was 0.05.