Ignite Creation Date:
2024-05-06 @ 8:24 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06364969
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-16
First Post:
2024-04-10
Brief Title:
Investigation of the Pruritogens of Liver-related Diseases
Sponsor:
Peking University
Organization:
Peking University
Study Overview
Official Title:
Investigation of the Pruritogens of Liver-related Diseases
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study hopes investigate the itch-inducing ability of different potential pruritogen candidates of cholestasis pruritus especially the intrahepatic cholestasis of pregnancy ICP In this study a combination of skin application and needle-free subcutaneous injection was used to investigate whether human endogenous molecules can cause itching And a questionnaire is used to quantify the intensity of different candidates-induced itch
Detailed Description:
Liver-related diseases are a large group of diseases that seriously affect people39s healthy life For example ICP the most common liver-related disease in pregnancy affects on average about 4 of pregnant women worldwide In a cohort study of 12200 eligible Chinese pregnant women the reported incidence of ICP was 606 ICP is harmful to the health of both pregnant women and fetuses For the fetus ICP directly affects the healthy growth and smooth delivery of the fetus Disease-related adverse events have been reported including preterm birth meconium contamination of amniotic fluid fetal hypoxia prolonged length of stay in neonatal unit and even stillbirth ICP has a serious impact on the physical and mental health of pregnant women typically severe pruritus This itching occurs mainly in the second and third trimesters of pregnancy usually the third trimester and tends to become progressively worse as the pregnancy progresses It is most commonly present on the palms and soles of the feet and some patients have generalized itching Moreover the itching was aggravated at night leading to severe insomnia Under the background of advocating multiple births in our country the effective prevention and treatment of such diseases is particularly important
At present there are no effective drugs for the treatment of ICP especially pruritus symptoms because the molecular mechanism of ICP and its pruritus is still unclear In this study we have identified several endogenous potential pruritogens that can activate human MRGPRX4 hX4 the potential itch receptor of ICP pruritus to mediate ICP pruritus based on a large number of previous cell and animal experiments On this basis the present study aims to evaluate the direct pruritic ability of different endogenous metabolites through human psychophysical experiments and subcutaneous administration of drugs to human subjects through a needle-free injection system
In detail this study includes two parts
1 Test whether the molecule causes itching i Skin application a certain amount of human endogenous metabolites progesterone sulfates are dissolved in Cold cream Avene France Firstly disposable medical disinfection cotton Lu Qing Food and Drug Supervision and Equipment Zhun word 2013 No 1640069 is used to disinfect the forearm flexor skin of healthy adult subjects The cream is then applied to the surface of the forearm double-blind requirements were followed During the experiment the subjects complete the itch and pain perception questionnaire At the end of the experiment the changes in the administration area are observed and recorded by the chief test including whether erythema and wheals occur
ii Needle-free subcutaneous injection a certain amount of human endogenous metabolites or FDA-approved drugs is dissolved in normal saline Firstly disposable medical disinfection cotton Lu Qing Food and Drug Supervision and Equipment Zhun word 2013 No 1640069 is used to disinfect the forearm skin of healthy adult subjects Then the drug solution is injected into the forearm surface of healthy adults using the clinical insulin injection needle-free injection system INJEX30 needle-free injection system China Food and Drug Supervision Instrument Jin Word 2013 No 3151260 The system mainly includes a disposable syringe a pressurizer a disposable ampoule and a disposable shock cushion During the experiment the subjects complete the itch and pain perception questionnaire At the end of the experiment the changes in the administration area are observed and recorded by the chief test including whether erythema and wheals occur
2 Molecular mechanisms of pruritus About 2g antihistamine cream doxepin hydrochloride cream H20041591 and placebo Cold cream Avene France are applied to the flexor muscles of the forearm about 4cm2 After 2 hours the drug is administered as a skin application or needle-free subcutaneous injection as described above 25ug of histamine positive control and the indicated doses of the aforementioned potentially itch-causing molecule double-blind requirements were followed The changes of the skin administration area whether there is erythema and wheals are observed during the experiment and the subjects complete the itch and pain perception questionnaires
3 Psychophysical experiments The general Labeled Magnitude Scale gLMS is used to estimate the level of itch or pain at the current moment relative to the level of itch or pain experienced by the subjects in previous situations Subjects chose from the following adjectives to describe the degree of itching or pain ① barely felt ② faint ③ mild ④ intense ⑤ very intense or ⑥ most intense
At present there are no effective drugs for the treatment of ICP especially pruritus symptoms because the molecular mechanism of ICP and its pruritus is still unclear In this study we have identified several endogenous potential pruritogens that can activate human MRGPRX4 hX4 the potential itch receptor of ICP pruritus to mediate ICP pruritus based on a large number of previous cell and animal experiments On this basis the present study aims to evaluate the direct pruritic ability of different endogenous metabolites through human psychophysical experiments and subcutaneous administration of drugs to human subjects through a needle-free injection system
In detail this study includes two parts
1 Test whether the molecule causes itching i Skin application a certain amount of human endogenous metabolites progesterone sulfates are dissolved in Cold cream Avene France Firstly disposable medical disinfection cotton Lu Qing Food and Drug Supervision and Equipment Zhun word 2013 No 1640069 is used to disinfect the forearm flexor skin of healthy adult subjects The cream is then applied to the surface of the forearm double-blind requirements were followed During the experiment the subjects complete the itch and pain perception questionnaire At the end of the experiment the changes in the administration area are observed and recorded by the chief test including whether erythema and wheals occur
ii Needle-free subcutaneous injection a certain amount of human endogenous metabolites or FDA-approved drugs is dissolved in normal saline Firstly disposable medical disinfection cotton Lu Qing Food and Drug Supervision and Equipment Zhun word 2013 No 1640069 is used to disinfect the forearm skin of healthy adult subjects Then the drug solution is injected into the forearm surface of healthy adults using the clinical insulin injection needle-free injection system INJEX30 needle-free injection system China Food and Drug Supervision Instrument Jin Word 2013 No 3151260 The system mainly includes a disposable syringe a pressurizer a disposable ampoule and a disposable shock cushion During the experiment the subjects complete the itch and pain perception questionnaire At the end of the experiment the changes in the administration area are observed and recorded by the chief test including whether erythema and wheals occur
2 Molecular mechanisms of pruritus About 2g antihistamine cream doxepin hydrochloride cream H20041591 and placebo Cold cream Avene France are applied to the flexor muscles of the forearm about 4cm2 After 2 hours the drug is administered as a skin application or needle-free subcutaneous injection as described above 25ug of histamine positive control and the indicated doses of the aforementioned potentially itch-causing molecule double-blind requirements were followed The changes of the skin administration area whether there is erythema and wheals are observed during the experiment and the subjects complete the itch and pain perception questionnaires
3 Psychophysical experiments The general Labeled Magnitude Scale gLMS is used to estimate the level of itch or pain at the current moment relative to the level of itch or pain experienced by the subjects in previous situations Subjects chose from the following adjectives to describe the degree of itching or pain ① barely felt ② faint ③ mild ④ intense ⑤ very intense or ⑥ most intense
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None