Investigating paracetamol safety in patients with low muscle mass

Pharmacokinetics and Safety of Treatment With Paracetamol in Children and Adults With Spinal Muscular Atrophy and Cerebral Palsy

This study is testing how safe paracetamol is for people with spinal muscular atrophy and cerebral palsy, including those in the ICU, to see how their age and body differences affect how the drug works.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 6 Years to 45 Years
• Sex: All
• Sponsor: Rigshospitalet, Denmark (Academic / other)
• Locations: 1 site (Copenhagen)
• Trial ID: NCT03648658 on ClinicalTrials.gov

What this trial studies

This study aims to investigate the pharmacokinetics and safety of paracetamol in patients with spinal muscular atrophy (SMA) and cerebral palsy (CP), including those admitted to the intensive care unit (ICU). The primary objective is to analyze the contributions of various metabolites of paracetamol in these patients compared to healthy controls. Additionally, the study will assess how age and physiological factors influence the pharmacokinetics of paracetamol. The research will involve both children and adults, ensuring a comprehensive understanding of the drug's effects across different age groups.

Who should consider this trial

Good fit: Ideal candidates include men, women, and children aged 6-45 diagnosed with SMA or CP, as well as healthy controls aged 18-45.

Not a fit: Patients with competing conditions that may compromise study results or those who are morbidly obese (BMI > 30) may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide critical insights into the safe use of paracetamol for patients with low muscle mass, improving pain management strategies.

How similar studies have performed: While there is limited data on paracetamol use specifically in SMA and CP populations, studies on its safety in other contexts have shown promising results.

Eligibility criteria

Inclusion Criteria:

* - Patients: Men, women and children diagnosed with/biochemically verified SMA and CP
* Patients admitted to the ICU: Men, women, children diagnosed with/biochemically verified SMA and CP
* Healthy controls: Need to be healthy, evaluated by the investigator.
* Age:

  * Children: 6-18 years
  * Adult patients: 18-45 years
  * Healthy controls: 18-45 years
  * ICU-admitted patients: 6-45 years
* Signed informed consent to participation in the trial

Exclusion Criteria:

* - Inability to understand the purpose of the trial or cooperate in the conduction of the experiments.

  o For the children this will concern of course the parents or the guardians of the child.
* Competing conditions at risk for compromising the results of the study.
* Participation in other trials that may interfere with the results.
* Intake of medications that may interfere with the results, evaluated by investigator.
* Pregnancy and breastfeeding.
* BMI \>30\*

  * In morbidly obese patients, the median area under the plasma concentration-time curve from 0 to 8 h. (AUC0-8h) of paracetamol is significantly smaller (p = 0.009), while the AUC0-8h ratios of the glucuronide, sulphate and cysteine metabolites to paracetamol are significantly higher (p = 0.043, 0.004 and 0.010, respectively). In this model, paracetamol CYP2E1-mediated clearance (cysteine and mercapturate) increased with lean body weight.

Where this trial is running

Copenhagen

• Copenhagen Neuromuscular Center — Copenhagen, Denmark (Recruiting)

Study contacts

• Principal investigator: Mette Cathrine Ørngreen, MD, DMSc — Md
• Study coordinator: Mette Cathrine Ørngreen, MD, DMSc

Conditions SMA II; Cerebral Palsy