Cerebral Palsy, Dyskinetic, Cerebral Palsy, Dystonic-Rigid, Dystonia, Dystonia, Secondary, Genetic Predisposition, Pediatric Disorder, Pharmacogenomic Drug Interaction, Trihexyphenidyl Adverse Reaction
Conditions
Keywords
Pediatric, Cerebral Palsy, Dystonia, Pharmacogenomics, Trihexyphenidyl
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.
Interventions
DRUGTrihexyphenidyl
6-week dose escalation up to 0.25mg/kg TID, followed by a 9-week maintenance period at this dose
Sponsors
Children's Mercy Hospital Kansas City
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Cmax between CYP2D6 and CYP2C19 phenotype groups | Baseline | Cmax will be measured in first-dose pharmacokinetic study on study day 1 |
| Difference in AUC0-n between CYP2D6 and CYP2C19 phenotype groups | Baseline | AUC0-n will be measured in first-dose pharmacokinetic study on study day 1 |
| Difference in AUC0-∞ between CYP2D6 and CYP2C19 phenotype groups | Baseline | AUC0-∞ will be measured in first-dose pharmacokinetic study on study day 1 |
| Recruitment percentage | Through study completion, an average of 2 years | Measure percent of participants who were approached for the study that enrolled in the study |
| Retention percentage | Through study completion, an average of 2 years | Measure percent of participants enrolled who completed the study |
| Dystonia Efficacy Measures Outcome Completion | Through study completion, an average of 2 years | Measure percent of participants enrolled who were able to complete each dystonia efficacy measure (see secondary outcome measures) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Adverse events will only include those that are determined to be related to the study drug. |
| Change from baseline in dystonia duration as measured by the Dyskinesia Impairment Scale, Version 2 (DIS-2) (exploratory) | Baseline, 16 weeks | 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%). |
| Change from baseline in dystonia amplitude as measured by the Dyskinesia Impairment Scale (exploratory) | Baseline, 16 weeks | 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%). |
| Change from baseline in dystonia as measured by the Quality of Upper Extremity Skills Test (QUEST) (exploratory) | Baseline, 16 weeks | 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. |
| Change in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory) | Baseline, 16 weeks | 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. |
| Change in priority scores in functional impact from baseline as measured by the Dyskinetic Cerebral Palsy Functional Impact Scale (D-FIS) (exploratory) | Baseline, 16 weeks | 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. |
| Change in patient-driven performance from baseline as measured by the Canadian Occupational Performance Measure (exploratory) | Baseline, 16 weeks | 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. |
| Change in patient-driven goal satisfaction from baseline as measured by the Canadian Occupational Performance Measure (exploratory) | Baseline, 16 weeks | 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. |
| 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 | Baseline, 16 weeks | 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. |
| Measure the acceptability of outcome measures at 16 weeks as measured by the Acceptability of Intervention Measure | 16 weeks | 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 |
| Change in disease severity from baseline as measured by the Patient Global Impression of Severity (PGI-S) (exploratory) | Baseline and 16 weeks | 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. |
| Change in overall status as measured by the Patient Global Impression of Change (PGI-C) | Week 16 | 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. |
Countries
United States
Contacts
CONTACTRose Gelineau-Morel, MD
CONTACTRachel Nass
PRINCIPAL_INVESTIGATORRose Gelineau-Morel, MD
Children's Mercy Kansas City
Outcome results
None listed