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| Name | Class |
|---|---|
| University of Kansas Medical Center | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Trihexyphenidyl | Drug | 6-week dose escalation up to 0.25mg/kg TID, followed by a 9-week maintenance period at this dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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, Version 2 (DIS-2) (exploratory) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rose Gelineau-Morel, MD | Contact | 816-302-3331 | rngelineaumorel@cmh.edu | |
| Rachel Nass | Contact | 8166011354 | rnass@cmh.edu |
| Name | Affiliation | Role |
|---|---|---|
| Rose Gelineau-Morel, MD | Children's Mercy Kansas City | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Mercy Hospital Kansas City | Recruiting | Kansas City | Missouri | 64108 | United States |
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.
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 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.
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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%). |
| 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 |
| 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. | 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. | Week 16 |
| ID | Term |
|---|---|
| D020022 | Genetic Predisposition to Disease |
| D020821 | Dystonic Disorders |
| D004421 | Dystonia |
| D002547 | Cerebral Palsy |
| ID | Term |
|---|---|
| D004198 | Disease Susceptibility |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009069 | Movement Disorders |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D001925 | Brain Damage, Chronic |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D014282 | Trihexyphenidyl |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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