Trihexyphenidyl for Cerebral Palsy

(TRIKE2 Trial)

Overseen By Rachel Nass

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Mercy Hospital Kansas City

Must not be taking: Trihexyphenidyl

Disqualifiers: Turning 18, Language barrier

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medicine called trihexyphenidyl to evaluate its effects in children with dystonic cerebral palsy. Researchers aim to understand how the body processes this medicine and whether genetics influence its effects. This information will guide the design of future studies. Children aged 5 to 17 with cerebral palsy and movement issues (dystonia) that impact daily life may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that trihexyphenidyl is likely to be safe for children with dystonic cerebral palsy?

Research has shown that trihexyphenidyl can cause side effects. Some people report restlessness, constipation, dry mouth, and trouble sleeping. However, this medicine is already approved for other uses, indicating it has been studied for safety in people. Although this trial is in an early stage, doctors will closely monitor any safety concerns. Participants should always consult their doctor if they have any worries. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cerebral palsy focus on managing symptoms through therapies like physical therapy, muscle relaxants, or botox injections to reduce muscle tightness. But trihexyphenidyl offers a different approach by targeting muscle stiffness and tremors with its anticholinergic effects. Researchers are excited about trihexyphenidyl because it modulates the action of neurotransmitters, potentially offering improved control over muscle movements. This could provide a new option for symptom management, especially for those who don't respond well to current treatments.

What evidence suggests that trihexyphenidyl might be an effective treatment for cerebral palsy?

Research on trihexyphenidyl for dystonic cerebral palsy has shown mixed results. Some studies have found that trihexyphenidyl did not reduce dystonia, which involves muscle contractions causing twisting and repetitive movements, nor did it improve arm function in children with cerebral palsy. However, another study reported significant improvements in dystonia, motor skills, and development in children using trihexyphenidyl. Additionally, combining trihexyphenidyl with clonazepam proved more effective than using trihexyphenidyl alone for treating dystonic cerebral palsy. These findings suggest that while trihexyphenidyl alone might not always work, it may be more effective when combined with other treatments. Participants in this trial will receive trihexyphenidyl following a dose escalation schedule to evaluate its effectiveness as a standalone treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

Rose Gelineau-Morel, MD

Principal Investigator

Children&#39;s Mercy Kansas City

Are You a Good Fit for This Trial?

This trial is for children aged 5-17 with dystonic cerebral palsy, where the condition interferes with their daily life. A parent or legal guardian must give informed permission for the child to participate.

Inclusion Criteria

I have cerebral palsy and dystonia that affects my daily activities.

I am between 5 and 17 years old.

My parent or guardian agrees to let me join the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive trihexyphenidyl following a dose escalation schedule to evaluate pharmacokinetics and genotype variations

16 weeks

Weekly visits for dose adjustments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Trihexyphenidyl

Trial Overview The study investigates how trihexyphenidyl, a medication used to treat dystonia in cerebral palsy patients, is processed by the body and if genetics affect this process. It will help design future trials.

How Is the Trial Designed?

Group I: Trihexyphenidyl Experimental Treatment 1 Intervention

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

Trihexyphenidyl is already approved in United States, European Union for the following indications:

Approved in United States as Artane for:

• Parkinson's disease
• Drug-induced extrapyramidal symptoms
• Dystonic cerebral palsy

Approved in European Union as Trihexyphenidyl for:

• Parkinson's disease
• Drug-induced extrapyramidal symptoms

Who Is Running the Clinical Trial?

Children's Mercy Hospital Kansas City

Lead Sponsor

Trials

261

Recruited

941,000+

University of Kansas Medical Center

Collaborator

Trials

527

Recruited

181,000+

Published Research Related to This Trial

In a study of 22 children with extrapyramidal cerebral palsy, trihexyphenidyl showed significant improvements in upper extremity function and expressive language, with many parents reporting high levels of positive change.

Younger children tended to respond better to trihexyphenidyl, indicating that age at treatment initiation may influence the effectiveness of the medication, particularly for fine motor skills and communication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age-dependent effects of trihexyphenidyl in extrapyramidal cerebral palsy. Hoon, AH., Freese, PO., Reinhardt, EM., et al.[2022]

A study involving 16 children with dystonic cerebral palsy found that trihexyphenidyl did not significantly improve dystonia or upper limb function compared to placebo, indicating limited efficacy for these outcomes.

The use of trihexyphenidyl was associated with a higher risk of adverse effects, suggesting that while it may be considered for treatment, its safety and effectiveness need further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl for dystonia in cerebral palsy. Harvey, AR., Baker, LB., Reddihough, DS., et al.[2022]

In a study involving 60 children aged 3-9 with dyskinetic cerebral palsy, the addition of gabapentin to trihexyphenidyl did not significantly improve the reduction of dystonia severity compared to trihexyphenidyl alone after 12 weeks.

Both treatment groups experienced similar side effects, with constipation being the most common, indicating that gabapentin does not provide additional therapeutic benefits in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gabapentin as Add-on Therapy to Trihexyphenidyl in Children with Dyskinetic Cerebral Palsy: A Randomized, Controlled Trial. Kumar, S., Shankar Kaushik, J., Verma, S., et al.[2023]

Trihexyphenidyl, commonly used to manage side effects from neuroleptics, has shown potential for abuse, as highlighted by two case reports.

A double-blind, placebo-controlled withdrawal study revealed a recognizable withdrawal syndrome, indicating that dependence on trihexyphenidyl should be considered in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl dependence. McInnis, M., Petursson, H.[2019]

A retrospective analysis of 31 children with dystonia showed that high-dose trihexyphenidyl (>0.5 mg/kg/day) led to reported improvements in motor function, especially in those without spasticity and with higher cognitive abilities.

Most caregivers noted improvements in areas like arm and hand function, with side effects being mostly transient, indicating that trihexyphenidyl can be a safe and effective treatment option for specific subgroups of children with dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl improves motor function in children with dystonic cerebral palsy: a retrospective analysis. Ben-Pazi, H.[2013]

In a pilot trial involving 23 children with cerebral palsy and secondary dystonia, high-dose trihexyphenidyl showed significant improvement in arm function after 15 weeks, indicating potential efficacy for this treatment.

However, some children with hyperkinetic dystonia experienced worsening symptoms at 9 weeks, suggesting that trihexyphenidyl may not be suitable for all types of dystonia, highlighting the need for further research to clarify its effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy. Sanger, TD., Bastian, A., Brunstrom, J., et al.[2022]

Trihexyphenidyl effectively improves gross motor function and fine motor control in patients with dystonic movement disorders, as demonstrated in an 8-year-old girl with dystonia following putamenal hemorrhages.

The drug works by inhibiting muscarinic cholinergic receptors in the basal ganglia and enhancing dopamine turnover, and it was well-tolerated with no reported adverse side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl in posthemorrhagic dystonia: motor and language effects. Pidcock, FS., Hoon, AH., Johnston, MV.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6494536/

Trihexyphenidyl for dystonia in cerebral palsy - PubMed Central We found no evidence that trihexyphenidyl was effective for reducing dystonia or improving upper arm function in children with cerebral palsy and dystonia.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06554288

Study Details | NCT06554288 | Pharmacogenomic ... This study looks at how a medicine called trihexyphenidyl works in children with dystonic cerebral palsy. The study aims to understand how trihexyphenidyl ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0887899424002297

Efficacy of Oral Trihexyphenidyl Plus Clonazepam Versus ... A combination of oral THP + CLZ proves to be more efficacious than using THP alone for the treatment of dystonic CP in children aged two to 14 years.

4. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012430.pub2/full?highlightAbstract=cerebr%7Cpalsi%7Cpalsy%7Ccerebral

Trihexyphenidyl for dystonia in cerebral palsy - Harvey, AR We found no evidence that trihexyphenidyl was effective for reducing dystonia or improving upper arm function in children with cerebral palsy ...

5. journals.sagepub.com journals.sagepub.com/doi/10.3233/PRM-210087

Trihexyphenidyl in young children with dystonic cerebral ... Trihexyphenidyl significantly improved dystonia, motor function and development in children with dystonic cerebral palsy in this study. Additional studies are ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0887899410004376

Use of Trihexyphenidyl in Children With Cerebral Palsy This study sought to review the benefits and tolerability of trihexyphenidyl in children with cerebral palsy, treated for dystonia or sialorrhea or both.

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111%2Fdmcn.15921

Pharmacological and neurosurgical management of ... In individuals with CP and generalized dystonia causing interference, we suggest against the routine use of oral/enteral trihexyphenidyl ( ...