Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
NCT Number: NCT06554288
Acronym: TRIKE2
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Pediatric Disorder|Genetic Predisposition|Dystonia, Secondary|Dystonia|Cerebral Palsy, Dystonic-Rigid|Cerebral Palsy, Dyskinetic|Trihexyphenidyl Adverse Reaction|Pharmacogenomic Drug Interaction
Interventions: DRUG: Trihexyphenidyl
Sponsor: Children's Mercy Hospital Kansas City
Collaborators: University of Kansas Medical Center
Sex: ALL
Age: CHILD
Enrollment: 40
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-15
Completion Date: 2026-10-31

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.

Primary Outcome Measures: Difference in Cmax between CYP2D6 and CYP2C19 phenotype groups, Cmax will be measured in first-dose pharmacokinetic study on study day 1, Baseline|Difference in AUC0-n between CYP2D6 and CYP2C19 phenotype groups, AUC0-n will be measured in first-dose pharmacokinetic study on study day 1, Baseline|Difference in AUC0-∞ between CYP2D6 and CYP2C19 phenotype groups, AUC0-∞ will be measured in first-dose pharmacokinetic study on study day 1, Baseline|Recruitment percentage, Measure percent of participants who were approached for the study that enrolled in the study, Through study completion, an average of 2 years|Retention percentage, Measure percent of participants enrolled who completed the study, Through study completion, an average of 2 years|Dystonia Efficacy Measures Outcome Completion, Measure percent of participants enrolled who were able to complete each dystonia efficacy measure (see secondary outcome measures), Through study completion, an average of 2 years
Secondary Outcome Measures: Number of participants with at least one adverse event as measured by the Safety Monitoring Uniform Report Form (SMURF), Adverse events will only include those that are determined to be related to the study drug., Through study completion, an average of 2 years|Change from baseline in dystonia duration as measured by the Dyskinesia Impairment Scale (exploratory), Duration of dystonia using subscale DIS-D are measured in 12 body regions during activity and rest.

Dystonia duration scores are measured on a 4-point scale from 0 to 4 with 0 being dystonia is absent and 4 being dystonia is always present (≥90%)., Baseline, 16 weeks|Change from baseline in dystonia amplitude as measured by the Dyskinesia Impairment Scale (exploratory), Amplitude of dystonia using subscale DIS-D are measured in 12 body regions during activity and rest.

Dystonia amplitude scores are measured on a 4-point scale from 0 to 4 with 0 being dystonia is absent and 4 being dystonia in maximal range of motion (≥90%)., Baseline, 16 weeks|Change from baseline in dystonia as measured by the Quality of Upper Extremity Skills Test (QUEST) (exploratory), Upper extremity function in 1 domain; grasp. 13 activities with item-level scores and three items for the tester to rate: hand function, spasticity, and cooperativeness. All scores are summed, and formulas are used to calculate percentages for this domain. Domain percentage is summed with a minimum score less than 0, and the maximum score is 100., Baseline, 16 weeks|Change in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory), Functional impact scores are measured on a 5-point scale from 0 to 4 with 0 being dyskinesia may be present but has no impact on the named activity, and 4 being dyskinesia is present and prevents child from doing a named activity, even with help. An "NA" option indicates the activity is difficult but NOT due to dyskinesia., Baseline, 16 weeks|Change in priority scores in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory), Priority scores are measured on a 4-point scale from 1 to 4 with 1 being an activity is not a priority and 4 being an activity is highest priority., Baseline, 16 weeks|Change in patient-driven performance from baseline as measured by the Canadian Occupational Performance Measure (exploratory), Performance scores are measured on a 10-point scale with 1 being not able to do an activity at all and 10 being able to do an activity extremely well., Baseline, 16 weeks|Change in patient-driven goal satisfaction from baseline as measured by the Canadian Occupational Performance Measure (exploratory), Satisfaction scores are measured on a 10-point scale with 1 being not satisfied at all with the way they do an activity to 10 being extremely satisfied with the way they do an activity., Baseline, 16 weeks|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, Scores for each domain and for the total survey are standardized and range from 0 to 100 with 0 being the worst and 100 being the best., Baseline, 16 weeks|Measure the acceptability of outcome measures at 16 weeks as measured by the Acceptability of Intervention Measure, Scores are measured on a 5-point scale from Completely Disagree to Completely Agree for items 1) The outcome measure meets my approval. 2) The outcome measure is appealing to me. 3) I like the outcome measure. 4) I welcome the outcome measure, 16 weeks