Determining the Pharmacogenetic Basis of Non-responsiveness to the Sedative Effects of Dexmedetomidine in Children

NCT ID: NCT04471402

Last Updated: 2022-03-16

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-07-20
• Study Completion Date: 2022-12-31

Brief Summary

Intranasal Dexmedetomidine is one of the sedative drugs of choice commonly used as an anxiolytic premedication for children for diagnostic or therapeutic procedures. However, some children do not achieve the level of sedation expected with the usual dose after an expected timeframe, leading to distress and costly time wasted.

In this study, we would try to identify a genetic basis to non-responders of Dexmedetomidine by comparing a chosen gene panel of 250 relevant genes between responders and non-responders to a standardized 3mcg/kg intranasal Dexmedetomidine.

Detailed Description

For most children, having to endure a diagnostic or therapeutic procedure in a hospital environment is a frightening and distressing experience, especially if it is accompanied by pain or discomfort. In an attempt to minimise the trauma and to maximise co-operation from the child, administration of a sedative is often requested by either the parent or the proceduralist. Some sedative agents may have the side effect reducing the child's efforts in breathing, causing inadequate oxygen to be delivered to and carbon dioxide removed from the body, a state that can be life threatening if left untreated. Other sedative agents may cause unpleasant sensations such as hallucinations or nausea while still others may have a paradoxical effect of exciting rather than sedating the child. Among the available agents that may be administered without the presence of an attendant anaesthesiologist, dexmedetomidine is an agent of choice with minimal incidence of the aforementioned effects. However, we have observed in a small proportion of children that dexmedetomidine does not see to be able to elicit a sedative response in the expected time and with the usual dose. It is possible that there is a genetic bas to this resistance and it would be of great use to be able to predict the non-responders ahead of time so an appropriate alternative may be selected without a trial and error approach.

In this project, children who would require Precedex as first-line sedation for radiological or pre-anaesthesia sedation are asked to participate by providing a buccal swab sample and have their genome (genetic makeup) characterised by target sequencing. They are standardized into receiving 3mcg/kg intranasal Precedex and are observed every 5 minutes afterwards for their level of sedation. They would be identified as 'fast responder', 'normal responder', 'slow responder' and 'definite non-responder'.

A gene panel of 250 relevant genes is chosen and compared between the different groups of responders and non-responders. We will then try to look for the differences between these groups and we will use this information to build a predictive model. This model will help to identify non-responders in the future and this would allow clinicians to prepare for an alternative approach to sedation. This would save time, distress to the child and parent and ultimately cost to the institution.

Conditions

Pharmacogenetic Study; Procedural Anxiety; Dexmedetomidine

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

All subjects recruited

All subjects recruited will be given 3mcg/kg intranasal Precedex through an atomiser, divided equally between two nostrils. They will be observed and sedation score will be recorded every 5 minutes according to the University of Michigan Sedation Scale (UMSS). Pulse oximetry and Blood pressure cuff will be applied whenever they accept these monitoring.

A buccal swab sample will be taken from all children and the identified genes will be analysed and compared between the different responders (fast, normal, slow or non-responders).

Precedex

Intervention Type: DRUG

Intranasal Precedex 3mcg/kg

Interventions

Precedex

Intranasal Precedex 3mcg/kg

Intervention Type: DRUG

Other Intervention Names

Dexmedetomidine

Eligibility Criteria

Inclusion Criteria

• Children who would receive 3mcg/kg intranasal Precedex as a first line sedative agent for radiological procedures or for pre-anaesthesia sedation
• Written informed consent from parent or legal guardian

Exclusion Criteria

• Known allergy or hypersensitivity to Precedex
• Pre-existing developmental delay
• Neurological impairment
• Autism
• Fever (temperature >/= 38.5c)
• Major organ dysfunction
• Cardiac arrhythmia
• Cardiac failure
• Subjects who would require a dose exceeding 100mcg if 3mcg/kg dose is achieved
• Subjects who have failed intranasal administration of Dexmedetomidine

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hong Kong Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vivian MY Yuen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hong Kong Children's Hospital

Locations

Hong Kong Children's Hospital

Hong Kong, , Hong Kong

Site Status: RECRUITING

Countries

Hong Kong

Central Contacts

Vivian MY Yuen, M.D.

Role: CONTACT

yuenmyv@ha.org.hk

+852 57413131

Jacqueline CK Tse, MBBS

Role: CONTACT

tck030@ha.org.hk

+852 57413200

Facility Contacts

Vivian MY Yuen, M.D.

Role: primary

yuenmyv@ha.org.hk

+852 57413131

Jacqueline CK Tse, MBBS

Role: backup

tck030@ha.org.hk

+852 57413200

Other Identifiers

Precedex PG study

Identifier Type: -

Identifier Source: org_study_id