Clinical trial NCT06554288: Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
Official title: Pharmacogenomic Contribution to the Biotransformation of Trihexyphenidyl and Development of a Precision Dosing Model for Children With Dystonia and Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pediatric Disorder
Genetic Predisposition
Dystonia, Secondary
Dystonia
Cerebral Palsy, Dystonic-Rigid
Cerebral Palsy, Dyskinetic
Trihexyphenidyl Adverse Reaction
Pharmacogenomic Drug Interaction
Keywords: Pediatric
Cerebral Palsy
Dystonia
Pharmacogenomics
Trihexyphenidyl
Lead sponsor: Children's Mercy Hospital Kansas City
Sponsor class: OTHER
Collaborators: name: University of Kansas Medical Center
First posted: 2024-08-15
Enrollment: 40
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study looks at how a medicine called trihexyphenidyl works in children with dystonic cerebral palsy. The study aims to understand how trihexyphenidyl is broken down and used in the body of pediatric patients and whether this is impacted by a person's genetics. Information from this study will also be used to design future clinical trials.

Detailed description: This is a 16-week single-arm nonrandomized pilot study of trihexyphenidyl in children with dystonic cerebral palsy (DCP) to 1) evaluate the pharmacokinetics (PK) of trihexyphenidyl (THP) and variation in PK parameters between CYP2D6 and CYP2C19 genotypes and 2) evaluate the feasibility of a future exposure-controlled clinical trial of THP.

Eligibility criteria: Inclusion Criteria:

* Ages 5-17 years of age
* Diagnosis of cerebral palsy and dystonia causing interference
* Parent/legal guardian of a child with a diagnosis of cerebral palsy and dystonia
* Parent/legal guardian is willing and able to provide informed permission/assent for the study

Exclusion Criteria:

* Previously or currently taking trihexyphenidyl
* Patients turning 18 years of age within the study period (16 weeks from Study Day 1)
* A language barrier for the patient that precludes communication and/or the ability to complete study-related requirements

Primary outcomes:
measure: Difference in Cmax between CYP2D6 and CYP2C19 phenotype groups
timeFrame: Baseline
measure: Difference in AUC0-n between CYP2D6 and CYP2C19 phenotype groups
timeFrame: Baseline
measure: Difference in AUC0-∞ between CYP2D6 and CYP2C19 phenotype groups
timeFrame: Baseline
measure: Recruitment percentage
timeFrame: Through study completion, an average of 2 years
measure: Retention percentage
timeFrame: Through study completion, an average of 2 years
measure: Dystonia Efficacy Measures Outcome Completion
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: Number of participants with at least one adverse event as measured by the Safety Monitoring Uniform Report Form (SMURF)
timeFrame: Through study completion, an average of 2 years
measure: Change from baseline in dystonia duration as measured by the Dyskinesia Impairment Scale (exploratory)
timeFrame: Baseline, 16 weeks
measure: Change from baseline in dystonia amplitude as measured by the Dyskinesia Impairment Scale (exploratory)
timeFrame: Baseline, 16 weeks
measure: Change from baseline in dystonia as measured by the Quality of Upper Extremity Skills Test (QUEST) (exploratory)
timeFrame: Baseline, 16 weeks
measure: Change in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory)
timeFrame: Baseline, 16 weeks
measure: Change in priority scores in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory)
timeFrame: Baseline, 16 weeks
measure: Change in patient-driven performance from baseline as measured by the Canadian Occupational Performance Measure (exploratory)
timeFrame: Baseline, 16 weeks
measure: Change in patient-driven goal satisfaction from baseline as measured by the Canadian Occupational Performance Measure (exploratory)
timeFrame: Baseline, 16 weeks
measure: Change in caregiver's perspective about their child in 4 domains: health status, comfort, wellbeing, functional abilities, and ease of caregiving from baseline as measured by Caregiver Priorities and Child Health Index of Life with Disabilities
timeFrame: Baseline, 16 weeks
measure: Measure the acceptability of outcome measures at 16 weeks as measured by the Acceptability of Intervention Measure
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: Children's Mercy Hospital Kansas City
state: Missouri
Study officials:
affiliation: Children&#39;s Mercy Kansas City
name: Rose Gelineau-Morel, MD
role: PRINCIPAL_INVESTIGATOR
References: