Trihexyphenidyl for Cerebral Palsy

(TRIKE2 Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Rose Gelineau-Morel, MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Children's Mercy Hospital Kansas City

Must not be taking: Trihexyphenidyl

Disqualifiers: Turning 18, Language barrier

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What evidence supports the effectiveness of the drug trihexyphenidyl for treating cerebral palsy?

Research shows that trihexyphenidyl can improve arm and hand function, as well as expressive language, in children with cerebral palsy, especially those without spasticity and with higher cognitive abilities. Younger children tend to respond better, and while some side effects may occur, they are generally not serious. ^{1 2 3 4 5}

Is trihexyphenidyl safe for use in children with cerebral palsy?

Trihexyphenidyl has been studied in children with cerebral palsy and is generally considered safe, though some children experienced nonserious side effects like chorea (involuntary movements), drug rash, and hyperactivity. Most side effects were temporary, but there is a potential for dependence, so it should be used with caution. ^{1 2 3 4 6}

How does the drug trihexyphenidyl differ from other treatments for cerebral palsy?

Trihexyphenidyl is unique because it is an anticholinergic drug that helps improve motor function in children with dystonic cerebral palsy, particularly in those without spasticity and with higher cognitive abilities. It works by inhibiting muscarinic cholinergic receptors in the brain, which can enhance dopamine activity, and is often used when oral medications are the first line of treatment for dystonia. ^{1 2 3 5 7}

Research Team

Rose Gelineau-Morel, MD

Principal Investigator

Children&#39;s Mercy Kansas City

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Trihexyphenidyl (Anticholinergic)

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.

Participant Groups

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

Who Is Running the Clinical Trial?

Children's Mercy Hospital Kansas City

Lead Sponsor

Trials

261

Recruited

941,000+

Dr. Alejandro Quiroga

Children's Mercy Hospital Kansas City

Chief Executive Officer

MD from Universidad Del Rosario, MBA

Dr. Doug Blowey

Children's Mercy Hospital Kansas City

Chief Medical Officer since 2023

MD from University of Kansas

University of Kansas Medical Center

Collaborator

Trials

527

Recruited

181,000+

Dr. Steve Stites

University of Kansas Medical Center

Chief Executive Officer

MD from University of Kansas School of Medicine

Dr. Matthias Salathe

University of Kansas Medical Center

Chief Medical Officer

MD from University of Kansas School of Medicine

Findings from Research

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 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]

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 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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Age-dependent effects of trihexyphenidyl in extrapyramidal cerebral palsy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl improves motor function in children with dystonic cerebral palsy: a retrospective analysis. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy. [2022]

4. India pubmed.ncbi.nlm.nih.gov

Gabapentin as Add-on Therapy to Trihexyphenidyl in Children with Dyskinetic Cerebral Palsy: A Randomized, Controlled Trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl in posthemorrhagic dystonia: motor and language effects. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl dependence. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Trihexyphenidyl for dystonia in cerebral palsy. [2022]