Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy

NCT06554288 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00003228
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (10)

• Number of participants with at least one adverse event as measured by the Safety Monitoring Uniform Report Form (SMURF)

  Through study completion, an average of 2 years

• Change from baseline in dystonia duration as measured by the Dyskinesia Impairment Scale (exploratory)

  Baseline, 16 weeks

• Change from baseline in dystonia amplitude as measured by the Dyskinesia Impairment Scale (exploratory)

  Baseline, 16 weeks

• Change from baseline in dystonia as measured by the Quality of Upper Extremity Skills Test (QUEST) (exploratory)

  Baseline, 16 weeks

• Change in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory)

  Baseline, 16 weeks

Study Arms (1)

Trihexyphenidyl

EXPERIMENTAL

Participants receive trihexyphenidyl following the dose escalation schedule below: Week 1: 0.05 mg/kg BID Week 2: 0.05 mg/kg TID Week 3: 0.1 mg/kg TID Week 4: 0.15 mg/kg TID Week 5: 0.20 mg/kg TID Week 6-15: 0.25 mg/kg TID

Drug: Trihexyphenidyl

Interventions

Trihexyphenidyl DRUG

6-week dose escalation up to 0.25mg/kg TID, followed by a 9-week maintenance period at this dose

Trihexyphenidyl

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Mercy Hospital Kansas City: lead
• University of Kansas Medical Center: collaborator

Study Sites (1)

Children's Mercy Hospital Kansas City

Kansas City, Missouri, 64108, United States

RECRUITING

MeSH Terms

Conditions

Genetic Predisposition to Disease; Dystonic Disorders; Dystonia; Cerebral Palsy

Interventions

Trihexyphenidyl

Condition Hierarchy (Ancestors)

Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Brain Damage, Chronic; Brain Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Rose Gelineau-Morel, MD

  Children's Mercy Kansas City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rose Gelineau-Morel, MD

CONTACT

816-302-3331; rngelineaumorel@cmh.edu

Rachel Nass

CONTACT

8166011354; rnass@cmh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 29, 2024
• First Posted: August 15, 2024
• Study Start: October 15, 2024
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: July 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data will be made available at the time of the associated publication or at the end of the study period, whichever comes first. The datasets made available through publications in PubMed will be made available indefinitely. Sharing of raw data upon request will be accommodated for at least 10 years. Once genetic data are published or uploaded to DASH or PharmVar, they will be available indefinitely.
• Access Criteria: Access to raw pharmacokinetic data/samples and genetic samples will be controlled because it will only be available upon request. For DASH, a request for study data can be submitted and managed within their system.

Locations

US (1)