Caffeine for Sedation Recovery in Children

Overseen By Zheng Xie, MD, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Disqualifiers: Arrhythmia, Congenital heart disease, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether caffeine can help children wake up faster after sedation with Dexmedetomidine, a common sedative used for MRI scans. Dexmedetomidine effectively sedates but can leave children feeling groggy and slow to recover. Researchers aim to speed up recovery by administering caffeine, helping children feel normal sooner. Eligible participants are children aged 3 to 12 years, weighing less than 33.3 kg, who require an MRI scan and have no heart issues or history of anesthesia problems. As a Phase 1, Phase 2 trial, this research focuses on understanding caffeine's effects in children and measuring its effectiveness in speeding up recovery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that caffeine can safely help children wake up faster after sedation. In earlier studies, caffeine did not increase children's blood pressure or heart rate and had no major side effects. It also helped them recover from anesthesia about 60% faster, which is promising for quicker wake-up times.

Dexmedetomidine is a common sedative due to its general safety, fewer breathing problems, and brain-protective properties. However, it can slow the heart rate and lower blood pressure. With the right dosage, these effects are milder and usually don't require additional treatment.

This evidence suggests that using caffeine to aid children's recovery from Dexmedetomidine sedation could be safe and effective. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard sedation recovery treatments for children, which typically do not include stimulants, this new approach uses caffeine. Researchers are excited about using caffeine because it acts as a central nervous system stimulant, potentially speeding up recovery times by counteracting sedation effects more quickly. Caffeine is also well-known, widely used, and has a favorable safety profile, making it an intriguing option for improving post-sedation recovery in pediatric patients.

What evidence suggests that caffeine could be an effective treatment for sedation recovery in children?

Research has shown that caffeine can help people wake up faster after anesthesia. In healthy adults, a dose of 7.5 mg of caffeine per kilogram of body weight accelerated awakening without major side effects. Another study found that caffeine also helped children wake up faster after surgery with general anesthesia, working effectively without causing problems. In this trial, some participants will receive caffeine alongside Dexmedetomidine (Dex) to determine if it helps children recover faster from sedation, which typically takes 30 to 60 minutes for them to wake up. Other participants will receive a placebo for comparison. ^{1 2 6 7 8}

Who Is on the Research Team?

Zheng Xie, MD,PhD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for pediatric patients who have undergone fast-track surgery and received Dexmedetomidine sedation during an MRI. They must be suitable for receiving caffeine as a potential recovery aid post-MRI.

Inclusion Criteria

My weight is 33.3 kg or less.

Undergo Magnetic Resonance Imaging (MRI) scan

I have never had a head injury.

Exclusion Criteria

History of head trauma

I have a history of heart, liver, or kidney diseases.

Prior difficulty with anesthesia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-3 days

1 visit (in-person or virtual)

Pre-sedation

Patient arrives in sedation suite, vitals obtained, and sedation plan reviewed

Same day as MRI

1 visit (in-person)

Sedation

Induction with Dexmedetomidine and monitoring during MRI procedure

Approximately 1-2 hours

1 visit (in-person)

Recovery

Patient receives study drug (caffeine or placebo) and is monitored until discharge criteria are met

Up to 2 hours

1 visit (in-person)

Follow-up

Patient receives follow-up call to assess recovery and satisfaction

1 day

1 call (virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Caffeine

Trial Overview The study tests if caffeine can speed up recovery from sedation with Dexmedetomidine in children after an MRI. It measures the time to wake up and meet discharge criteria compared to usual care without caffeine.

How Is the Trial Designed?

Group I: Dexmedetomidine +/- Caffeine Sedation Experimental Treatment 1 Intervention

Eligible subjects will be given 15 mg/kg caffeine citrate (equivalent to \~5 mg/ kg caffeine base) \~ 15 min after terminating Dex's infusion.

Group II: Dexmedetomidine +/- Placebo Sedation Placebo Group 1 Intervention

Eligible subjects will be given 9 mg/ml saline placebo) \~ 15 min after terminating Dex's infusion.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study evaluating pain relief after wisdom tooth surgery, combinations of hydrocodone-acetaminophen and codeine-acetaminophen were found to be effective for managing moderate to severe pain, showing significant analgesic effects compared to placebo.

All active medications provided similar levels of pain relief, and any adverse effects experienced were temporary and primarily linked to the central nervous system effects of the medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of the analgesic efficacy of three opioid-analgesic combinations in postoperative oral surgery pain. Forbes, JA., Bowser, MW., Calderazzo, JP., et al.[2020]

The combination of paracetamol (1,000 mg) and caffeine (130 mg) (PCF) was found to be well-tolerated and effective for treating tension-type headache (TTH) in an Italian population, based on a multicenter, randomized, double-blind, placebo-controlled trial.

Both PCF and naproxen sodium (550 mg) showed significant efficacy compared to placebo, but there was no significant difference in effectiveness between PCF and naproxen, indicating that PCF is a viable alternative for acute TTH treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and efficacy of a combination of paracetamol and caffeine in the treatment of tension-type headache: a randomised, double-blind, double-dummy, cross-over study versus placebo and naproxen sodium. Pini, LA., Del Bene, E., Zanchin, G., et al.[2018]

In a study involving 60 young, healthy volunteers, tramadol, dextropropoxyphene, and a commercial drug mixture all significantly increased pain thresholds in dental pulp, indicating their analgesic efficacy.

There was no significant difference in the pain-relieving effects among the three drugs, suggesting that they may be equally effective for managing pain in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of tramadol and other analgesics on the pain threshold in human dental pulp (author's transl)]. Rost, A., Schenck, EG.[2006]

In a study involving 1743 patients, the fixed combination of acetylsalicylic acid, paracetamol, and caffeine (Thomapyrin) provided significantly faster pain relief for tension-type headaches and migraines compared to other treatments, including placebo and individual components.

All treatments were well tolerated with a low incidence of adverse events, indicating that the combination therapy is not only effective but also safe for patients accustomed to using non-prescription analgesics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study. Diener, HC., Pfaffenrath, V., Pageler, L., et al.[2013]

The combination of indomethacin, caffeine, and prochlorperazine (IndoProCaf) effectively reverses hyperalgesia in mice, demonstrating a significant increase in pain threshold after treatment, even at doses much lower than typical analgesics.

IndoProCaf showed superior efficacy in reducing pain compared to the individual components, indicating that the combination therapy may be particularly effective for conditions like migraine, where hyperalgesia is present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indomethacin, caffeine and prochlorperazine alone and combined revert hyperalgesia in in vivo models of migraine. Galeotti, N., Ghelardini, C., Grazioli, I., et al.[2019]

In a multi-center randomized controlled trial involving migraine patients, the combination of paracetamol (1,000 mg) and caffeine (130 mg) was found to be as effective as sumatriptan (50 mg) in relieving migraine pain.

Both treatments showed similar tolerability, with no significant differences in adverse events reported, confirming that the combination of paracetamol and caffeine is a safe alternative for migraine relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of tolerability and efficacy of a combination of paracetamol + caffeine and sumatriptan in the treatment of migraine attack: a randomized, double-blind, double-dummy, cross-over study. Pini, LA., Guerzoni, S., Cainazzo, M., et al.[2021]

The fixed combination of indomethacin, prochlorperazine, and caffeine (Difmetré®) has been shown to be effective and well tolerated for treating migraine and episodic tension-type headache in adult patients, based on randomized, multicenter studies.

Rectal formulations of this combination were found to be significantly more effective than sumatriptan for migraine treatment, while oral formulations showed similar efficacy to sumatriptan and nimesulide, providing additional options for acute headache management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indomethacin/prochlorperazine/caffeine: a review of its use in the acute treatment of migraine and in the treatment of episodic tension-type headache. Hoy, SM., Scott, LJ.[2021]

In phase 3 trials, sumatriptan/naproxen sodium (Treximet®) was found to be significantly more effective than placebo in providing pain relief for migraines in both adolescents and adults, with a notable increase in the number of patients who were pain-free at 2 hours after treatment.

The combination medication was generally well tolerated, with low rates of treatment-related adverse events (≤11% in adolescents and ≤22% in adults), making it a safe and effective option for acute migraine treatment that may also enhance patient adherence due to its fixed-dose formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sumatriptan/Naproxen Sodium: A Review in Migraine. Syed, YY.[2018]

Thomapyrin, a popular over-the-counter analgesic in Germany for 50 years, combines acetylsalicylic acid, paracetamol, and caffeine, demonstrating a 1.4-fold increase in analgesic effectiveness due to the synergistic effects of its ingredients.

The combination does not alter the side effect profile compared to individual components, indicating a favorable benefit/risk ratio, making it suitable for self-medication in managing various types of pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness of fixed analgesic combinations exemplified by thomapyrin]. Aicher, B., Kraupp, O.[2013]

A multicenter, double-blind, placebo-controlled trial was conducted to evaluate the effectiveness and safety of combining ibuprofen with caffeine for treating tension-type headaches, building on previous evidence of caffeine's analgesic properties.

The study aims to confirm the pain-relieving effects of caffeine and explore how tension-type headaches can serve as a useful model for pain research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of ibuprofen plus caffeine to treat tension-type headache. Diamond, S., Freitag, FG.[2019]

Codeine has seen a significant decline in use for managing moderate to severe pain in children due to safety concerns, leading to a search for alternative opioids.

Oral morphine is currently the most well-supported alternative to codeine for children, with more evidence of its safety and efficacy, while further research is needed on other opioids and non-opioid pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of oral opioids to control children's pain in the post-codeine era. Rieder, MJ., Jong, G'.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8919303/

Effect of Caffeine on the Acceleration of Emergence from ... This study aimed to determine whether or not caffeine can accelerate awakening after anesthesia in children undergoing inguinal herniorrhaphy under GA.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5462883/

Caffeine combined with sedative/anesthetic drugs triggers ... These data suggest that the CAF + midazolam cocktail increases neurotoxicity in the immature mouse brain in substrates critical for normal brain ...

3. journals.lww.com journals.lww.com/joacp/fulltext/2023/39040/caffeine___essentials_for_anaesthesiologists__a.3.aspx

Caffeine – Essentials for anaesthesiologists: A narrative... Caffeine has a multitude of uses in anaesthesia, and numerous studies have evaluated its efficacy and usefulness in various aspects of anaesthesia and medical ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1875957217301778

Caffeine citrate – Is it a silver bullet in neonatology? However, many studies have shown higher doses of caffeine to be more effective with negligible adverse effects.

5. fda.gov fda.gov/media/181638/download

Cafcit Pediatric Postmarketing Safety Review The efficacy of CAFCIT for longer periods of treatment has not been established. Safety and efficacy of CAFCIT for use in the prophylactic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3949308/

Caffeine accelerates recovery from general anesthesia - PMC Caffeine dramatically sped recovery from anesthesia by ∼60%. Figure 6B shows the average recovery time at different concentrations of caffeine. Figure 6B, ...

7. publications.aap.org publications.aap.org/pediatrics/article/143/6/e20191000/37173/Guidelines-for-Monitoring-and-Management-of

Guidelines for Monitoring and Management of Pediatric ... The child who has received moderate sedation must be observed in a suitably equipped recovery area, which must have a functioning suction apparatus as well as ...

8. ctv.veeva.com ctv.veeva.com/study/dex-caffeine-sedation-in-a-post-surgery-recovery-in-a-pediatric-population

Dex +/- Caffeine Sedation in a Post-MRI Recovery in a ... With this Dex sedation protocol, these pediatric patients usually take an average of 45 minutes (30-60 minutes) to wake and become alert and up ...