Pediatric DisorderPhase 1TRIKE2NCT06554288
Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
A Phase 1 study testing Trihexyphenidyl in people with Pediatric Disorder and Genetic Predisposition, run by Children's Mercy Hospital Kansas City at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Pediatric Disorder, Genetic Predisposition, Dystonia, Secondary
- What is being tested?
- Trihexyphenidyl
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Oct 2024to 31 Dec 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Mercy Hospital Kansas City
Kansas City, Missouri, 64108
Rachel Nass, 816-601-1354, rnass@cmh.edu
Rose Gelineau-Morel, MD
About this study
Official title: Pharmacogenomic Contribution to the Biotransformation of Trihexyphenidyl and Development of a Precision Dosing Model for Children With Dystonia and Cerebral Palsy
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.
Read the 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.
- Conditions
- Pediatric Disorder, Genetic Predisposition, Dystonia, Secondary, Dystonia, Cerebral Palsy, Dystonic-Rigid, Cerebral Palsy, Dyskinetic
- Being tested
- Trihexyphenidyl
- Keywords
- Pediatric, Cerebral Palsy, Dystonia, Pharmacogenomics, Trihexyphenidyl
- Medical subject headings
- Genetic Predisposition to Disease, Dystonic Disorders, Dystonia, Cerebral Palsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrihexyphenidylDrug
6-week dose escalation up to 0.25mg/kg TID, followed by a 9-week maintenance period at this dose
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Trihexyphenidyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Cmax between CYP2D6 and CYP2C19 phenotype groups
Cmax will be measured in first-dose pharmacokinetic study on study day 1
Measured: 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
Measured: Baseline
Difference in AUC0-∞ between CYP2D6 and CYP2C19 phenotype groups
AUC0-∞ will be measured in first-dose pharmacokinetic study on study day 1
Measured: Baseline
Recruitment percentage
Measure percent of participants who were approached for the study that enrolled in the study
Measured: Through study completion, an average of 2 years
Retention percentage
Measure percent of participants enrolled who completed the study
Measured: 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)
Measured: Through study completion, an average of 2 years
Secondary outcomes (12)
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.
Measured: Through study completion, an average of 2 years
Change from baseline in dystonia duration as measured by the Dyskinesia Impairment Scale, Version 2 (DIS-2) (exploratory)
The Dyskinesia Impairment Scale, Version 2 (DIS-2) is an updated version of the Dyskinesia Impairment Scale used to assess dystonia across multiple body regions.
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%).
Measured: 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%).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 16 weeks
Change in disease severity from baseline as measured by the Patient Global Impression of Severity (PGI-S) (exploratory)
The Patient Global Impression of Severity (PGI-S) is a single-item outcome measure assessing overall disease severity over the past week. Clinicians rate the participant's condition on a 5-point scale: none, mild, moderate, severe, or very severe. Higher scores indicate greater perceived severity.
Measured: Baseline and 16 weeks
Change in overall status as measured by the Patient Global Impression of Change (PGI-C)
The Patient Global Impression of Change (PGI-C) is a single-item outcome assessing overall change since the start of the study. Participants and the clinician rate the participant's condition on a 7-point Likert scale ranging from very much improved to very much worse.
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2024
- Study start15 Oct 2024
- Primary completion30 Nov 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Mercy Hospital Kansas City
- Sponsor type
- University, hospital or other
- Collaborators
- University of Kansas Medical Center
- Responsible party
- Principal investigator, Rose Gelineau-Morel, Children's Mercy Hospital Kansas City
- Investigators
- Rose Gelineau-Morel, MD, Principal investigator, Children's Mercy Kansas City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06554288
- Sponsor's protocol ID
- STUDY00003228
- Acronym
- TRIKE2
- Status last verified
- Jun 2026
- First submitted
- 29 Jul 2024
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Pharmacokinetic data, including genotypes and THP levels, will be in publications for analysis replication. This will include participant genotypes and corresponding levels of THP, R-THP, and S-THP. Raw data and technical duplicates are available on request for result transparency and clinical trial design. CYP2D6 and CYP2C19 data will also be published; raw sequences go to NICHD's Data Hub (https://dash.nichd.nih.gov/), new haplotypes to PharmVar (https://www.pharmvar.org/). Recruitment, retention, and scientific methods outcomes will be published to guide future THP trials, though the study isn't powered for efficacy endpoints.