Chronic Pruritus
Conditions
Keywords
arsenic exposure, naloxone, placebo, single-blind randomized trial
Brief summary
The purpose of this study is to assess the efficacy and safety of sublingual naloxone in the treatment of chronic itch in patients under arsenic exposure.
Detailed description
This study aims to determine the efficacy and safety of sublingual naloxone in the treatment of chronic, refractory itch in patients under long-term arsenic exposure. In this study, 120 subjects with a moderate-to-severe symptom of itching (numeric rating scale, NRS≥3) will be recruited and randomly treated with either sublingual naloxone (60 subjects) or placebo (60 subjects). The severity of itching will be evaluated in the wash out phase, baseline, and one week after the treatment through reporting of subjective symptomatology (itch NRS) via the interview. Quality of sleep measured by the Pittsburgh Sleep Quality Index (PSQI) and Dermatology Life Quality Index (DLQI) will serve as the secondary outcome.
Interventions
DRUGNaloxone
Naloxone at an sublingual dose of 0.4 mg daily for one week will be given to each subject. Subjects will self-administer the drug at supervision in the primary care center.
DRUGPlacebo
Placebo will be given to each subject for one week. Subjects will self-administer the drug at supervision in the primary care center.
Sponsors
Xiangya Hospital of Central South University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The participants will not be informed whether the drug they received is naloxone or placebo. The investigators will remove the package of the drugs and use the unified package for both of the drugs.
Intervention model description
Participants will be randomly assigned to two arms using a computer-generalized sequence of random numbers.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or over and without diseases except arsenic-related pruritus 2. Ability to study protocol and to give informed consent by himself/herself voluntarily 3. The number of male or female subjects is required more than 1/3 of the total number of subjects 4. Numeric Rating Sscale≥3 at the baseline 5. Subjects taking hormone-containing medications must be on a stable dose for 6 months prior to study start to avoid any confounding influence on sensory and pain perception
Exclusion criteria
1. Use of oral anti-inflammatory medications for 2 weeks prior to the study start. 2. Use of oral anti-histamines for 2 weeks prior to the study start. 3. Use of topical or oral anti-pruritic agents for 2 weeks prior to the study start. 4. Use of oral neuromodulatory agents for 2 months prior to study start. 5. Current use of chronic pain medications (including opioids, antidepressants and anti-epileptic drugs). 6. Use of nicotine-containing products for the past 6 months prior to study start. 7. History of basic itchy dermatological diseases before such as eczema wich may influence the judgement of drug efficacy. 8. Unstable thyroid function within the past 6 months prior to study start to exclude thyroid-related neuropathy. 9. Known history of central or peripheral nervous system dysfunction. 10. History of acute hepatitis, chronic liver disease or end stage liver disease. 11. History of human immunodeficiency virus (HIV) or acquired immune deficiency syndrome. 12. History of neuropathy associated with chronic obstructive pulmonary disease, diabetes mellitus, documented exposure to organophosphates or heavy metals or polychlorinated biphenyls. 13. Known nutritional deficiency (vitamin B12, vitamin D, iron or zinc) within 3 months prior to the study start. 14. Use of illicit drugs within the past 6 months prior to study start. 15. Lyme disease, porphyria, rheumatoid arthritis, Hansen's disease (leprosy) or use of antineoplastic chemotherapeutic agents. 16. Patients considered by researchers that are not suitable to the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numeric Rating Scale for Itch | 1 week | Participants will be invited to report the severity of itch using the Numeric Rating Scale (NRS) for Itch at the baseline and week 1 of the trial. Numeric Rating Scale (NRS) for Itch is a self-reported scale to measure the intensity of itch, with a range of score from 0 to 10. Higher scores indicate stronger itching, with a score of 1 or 2 suggesting mild itching, a score between 3 and 6 suggesting moderate itching, and a greater than 7 indicating severe itching. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pittsburgh Sleep Quality Index (PSQI) | 1 week | Measured by the Pittsburgh Sleep Quality Index (PSQI) at baseline and week 1 of the trial. Each component score of the PSQI ranges from 0 to 3, with 3 indicating the greatest dysfunction or disturbance. The seven component scores are then summed to obtain a global PSQI score, which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties. |
| Serological Indicator | 1 week | Level of serum beta-endorphin will be tested at baseline and week 1 of the trial |
| Dermatology Life Quality Index (DLQI) | 1 week | Dermatology Life Quality Index (DLQI) at baseline and week 1 of the trial. It consists of ten questions which ask about symptoms, feelings, daily activities, leisure, work, school, personal relationships, and treatment. Every question asked relates to the previous week. The user can tick a box in either: 'not at all', 'a little', 'a lot' or 'very much'. Questions are scored from 0 to 3 and totalled, giving an overall score out of 30. The final score ranges from 0 (no impact on quality of life) to 30 (maximum impairment). |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Naloxone Naloxone at an sublingual dose of 0.4 mg daily will be given to each subject.
Naloxone: Naloxone at an sublingual dose of 0.4 mg daily for one week will be given to each subject. Subjects will self-administer the drug at supervision in the primary care center. | 62 |
| Placebo Sublingual placebo will be given to each subject.
Placebo: Placebo will be given to each subject for one week. Subjects will self-administer the drug at supervision in the primary care center. | 64 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lack of Efficacy | 9 | 30 |
Baseline characteristics
| Characteristic | Naloxone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 9 | 60 years STANDARD_DEVIATION 9 | 59 years STANDARD_DEVIATION 9 |
| Numeric Rating Scale for Itch | 8.18 units on a scale STANDARD_DEVIATION 1.77 | 8.58 units on a scale STANDARD_DEVIATION 1.56 | 8.38 units on a scale STANDARD_DEVIATION 1.66 |
| Race/Ethnicity, Customized Chinese | 62 Participants | 64 Participants | 126 Participants |
| Region of Enrollment China | 62 participants | 64 participants | 126 participants |
| Sex: Female, Male Female | 27 Participants | 26 Participants | 53 Participants |
| Sex: Female, Male Male | 35 Participants | 38 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 64 |
| other Total, other adverse events | 3 / 62 | 2 / 64 |
| serious Total, serious adverse events | 0 / 62 | 0 / 64 |
Outcome results
Primary
Numeric Rating Scale for Itch
Participants will be invited to report the severity of itch using the Numeric Rating Scale (NRS) for Itch at the baseline and week 1 of the trial. Numeric Rating Scale (NRS) for Itch is a self-reported scale to measure the intensity of itch, with a range of score from 0 to 10. Higher scores indicate stronger itching, with a score of 1 or 2 suggesting mild itching, a score between 3 and 6 suggesting moderate itching, and a greater than 7 indicating severe itching.
Time frame: 1 week
Population: Intention-to-treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Numeric Rating Scale for Itch | 6.42 score on a scale (0~10) | Standard Deviation 2.15 |
| Placebo | Numeric Rating Scale for Itch | 7.8 score on a scale (0~10) | Standard Deviation 1.99 |
Secondary
Dermatology Life Quality Index (DLQI)
Dermatology Life Quality Index (DLQI) at baseline and week 1 of the trial. It consists of ten questions which ask about symptoms, feelings, daily activities, leisure, work, school, personal relationships, and treatment. Every question asked relates to the previous week. The user can tick a box in either: 'not at all', 'a little', 'a lot' or 'very much'. Questions are scored from 0 to 3 and totalled, giving an overall score out of 30. The final score ranges from 0 (no impact on quality of life) to 30 (maximum impairment).
Time frame: 1 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naloxone | Dermatology Life Quality Index (DLQI) | 9.2 units on a scale (0-30) | Standard Deviation 6.7 |
| Placebo | Dermatology Life Quality Index (DLQI) | 12.1 units on a scale (0-30) | Standard Deviation 6.2 |
Secondary
Pittsburgh Sleep Quality Index (PSQI)
Measured by the Pittsburgh Sleep Quality Index (PSQI) at baseline and week 1 of the trial. Each component score of the PSQI ranges from 0 to 3, with 3 indicating the greatest dysfunction or disturbance. The seven component scores are then summed to obtain a global PSQI score, which ranges from 0 to 21. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties.
Time frame: 1 week
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naloxone | Pittsburgh Sleep Quality Index (PSQI) | 9.5 units on a scale (0-21) |
| Placebo | Pittsburgh Sleep Quality Index (PSQI) | 10.0 units on a scale (0-21) |
Secondary
Serological Indicator
Level of serum beta-endorphin will be tested at baseline and week 1 of the trial
Time frame: 1 week