Melatonin for Delirium
(DELIRE-ICU Trial)
Recruiting in Palo Alto (17 mi)
Overseen byFrançois Marquis, M.D., M.A.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ciusss de L'Est de l'Île de Montréal
Must not be taking: Melatonin
Disqualifiers: Severe brain injury, Schizophrenia, Bipolar, Seizures, others
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial aims to test if melatonin can help reduce delirium in critically ill ICU patients by improving their sleep. Delirium is common in these patients, and there are no effective drug treatments currently available. By regulating sleep, melatonin might shorten the duration of delirium episodes. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. However, you cannot have used melatonin within 24 hours before joining the trial.
What data supports the effectiveness of the drug melatonin for delirium?
Research indicates that melatonin may help prevent and manage delirium in older adults, although it doesn't seem to reduce the severity of delirium. Additionally, a similar drug, ramelteon, has shown benefits in preventing delirium, suggesting that melatonin might also be effective.
12345Is melatonin safe for humans?
Melatonin and its agonists, like ramelteon, have been well tolerated in studies, with few adverse effects reported. In trials for conditions like delirium and insomnia, melatonin was generally safe, with mild side effects such as nausea and dizziness occurring in a small number of cases.
12678How does melatonin differ from other drugs for delirium?
Melatonin is unique in its use for delirium because it is a natural hormone that helps regulate sleep-wake cycles, and it is well-tolerated with few side effects. Unlike other drugs, melatonin focuses on correcting circadian rhythm disruptions, which are thought to contribute to delirium, rather than directly targeting symptoms or behaviors.
128910Eligibility Criteria
Adults over 18 in the ICU with a recent delirium score of at least 4, expected to stay in the ICU for more than 48 hours. Not eligible if they have severe brain injuries, major cognitive disorders, certain psychiatric diagnoses, seizures, coma, are pregnant or breastfeeding, took melatonin recently or can't take oral meds.Inclusion Criteria
Your ICDSC score is 4 or higher for up to 48 hours before being chosen by chance to be in the study.
I am 18 or older and have been admitted to the ICU.
I expect to stay in the ICU for more than 48 hours.
Exclusion Criteria
My doctor expects my illness to significantly impact my life expectancy in the short term.
I was diagnosed with delirium before being admitted to the ICU.
I do not have active seizures, coma, aphasia, or severe intellectual disability.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive melatonin 9 mg or placebo daily at 21:00 to treat delirium in the ICU
14 days
Daily monitoring in ICU
Follow-up
Participants are monitored for safety and effectiveness after treatment during their stay in the ICU and after transfer to another unit
14 days
Participant Groups
The trial is testing whether giving melatonin to critically ill adults helps treat delirium compared to a placebo. It's set up as a small-scale study first to see if it's possible to do a larger one later.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Enteral melatonin 9 mgExperimental Treatment1 Intervention
Melatonin 9 mg from a 1 mg/mL oral suspension of melatonin in ORA-BLEND SF® (sugar-free flavoured suspending vehicle). Final volume in the oral syringe will be 9 mL.
Group II: Enteral placeboPlacebo Group1 Intervention
ORA-BLEND SF® (sugar-free flavoured suspending vehicle). Final volume in the oral syringe will be 9 mL.
Melatonin is already approved in European Union, European Union, United States for the following indications:
🇪🇺 Approved in European Union as Circadin for:
- Insomnia in adults aged 55 and over
- Sleep disorders in children with autism spectrum disorder
🇪🇺 Approved in European Union as Slenyto for:
- Insomnia in children and adolescents aged 2-18 with autism spectrum disorder
🇺🇸 Approved in United States as Melatonin for:
- Sleep disorders in children with autism spectrum disorder
- Insomnia in adults
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hopital Maisonneuve-RosemontMontréal, Canada
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Who Is Running the Clinical Trial?
Ciusss de L'Est de l'Île de MontréalLead Sponsor
Maisonneuve-Rosemont HospitalCollaborator
References
Melatonin and melatonin agonist for delirium in the elderly patients. [2022]The objective of this review is to summarize the available data on the use of melatonin and melatonin agonist for the prevention and management of delirium in the elderly patients from randomized controlled trials (RCTs). A systematic search of 5 major databases PubMed, MEDLINE, PsychINFO, Embase, and Cochrane Library was conducted. This search yielded a total of 2 RCTs for melatonin. One study compared melatonin to midazolam, clonidine, and control groups for the prevention and management of delirium in individuals who were pre- and posthip post-hip arthroplasty. The other study compared melatonin to placebo for the prevention of delirium in older adults admitted to an inpatient internal medicine service. Data from these 2 studies indicate that melatonin may have some benefit in the prevention and management of delirium in older adults. However, there is no evidence that melatonin reduces the severity of delirium or has any effect on behaviors or functions in these individuals. Melatonin was well tolerated in these 2 studies. The search for a melatonin agonist for delirium in the elderly patients yielded 1 study of ramelteon. In this study, ramelteon was found to be beneficial in preventing delirium in medically ill individuals when compared to placebo. Ramelteon was well tolerated in this study.
Melatonin Receptor Agonists for Delirium Prevention. [2022]To review the prospective controlled trials available for the use of melatonin receptor agonists for delirium prevention.
Marked improvement in delirium with ramelteon: five case reports. [2022]Delirium is a common and serious acute neuropsychiatric syndrome characterized by inattention and global cognitive dysfunction. Delirium is associated with higher morbidity, higher mortality and longer hospitalization, but its aetiology remains unclear. We successfully treated five cases of delirium within 1 day with ramelteon, a novel selective melatonin receptor agonist. This suggests that correction of the circadian rhythm disturbance, one of the main symptoms of delirium, plays a crucial role in its treatment and sheds new light on a therapeutic strategy for treatment of delirium.
Melatonin and melatonin-receptor agonists to prevent delirium in hospitalized older adults: An umbrella review. [2022]Alterations in circadian rhythm play an important role in the development of delirium. In this umbrella review, we examined the efficacy of melatonin and ramelteon for delirium prevention in hospitalized older adults.
Melatonin and Ramelteon for the treatment of delirium: A systematic review and meta-analysis. [2023]To assess the efficacy of melatonin and melatonergic agonist for the treatment of delirium in hospitalized patients.
Prophylactic Use of Ramelteon for Delirium in Hospitalized Patients: A Systematic Review and Meta-Analyses. [2023]Small prospective studies, case reports, as well as some randomized placebo-controlled trials and previous meta-analyses have shown that ramelteon, a melatonin agonist, may reduce the risk of developing delirium.
Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. [2021]Surveillance studies are useful to evaluate how a new medicinal product performs in everyday treatment and how the patient who takes it feels and functions, thereby determining the benefit/risk ratio of the drug under real-life conditions. Prolonged-release melatonin (PRM; Circadin) was approved in Europe for the management of primary insomnia patients age 55 years or older suffering from poor quality of sleep. With traditional hypnotics (e.g. benzodiazepine-receptor agonists), there are concerns about rebound insomnia and/or withdrawal symptoms. We report data from a postmarketing surveillance study in Germany on the effects of 3 weeks of treatment with PRM on sleep in patients with insomnia during treatment and at early (1-2 days) and late (around 2 weeks) withdrawal. In total, 653 patients (597 evaluable) were recruited at 204 sites (mean age 62.7 years, 68% previously treated with hypnotics, 65% women). With PRM treatment, the mean sleep quality (on a scale of 1-5 on which 1 is very good and 5 is very bad) improved from 4.2 to 2.6 and morning alertness improved from 4.0 to 2.5. The improvements persisted over the post-treatment observation period. Rebound insomnia, defined as a one-point deterioration in sleep quality below baseline values, was found in 3.2% (early withdrawal) and 2.0% (late withdrawal). Most of the patients (77%) who used traditional hypnotics before PRM treatment had stopped using them and only 5.6% of naive patients started such drugs after PRM discontinuation. PRM was well tolerated during treatment and the most frequently reported adverse events were nausea (10 patients, 1.5%), dizziness, restlessness and headache (five patients each,
Ramelteon for the treatment of delirium in elderly patients: a consecutive case series study. [2022]Melatonin is effective in the prevention and treatment of delirium. Ramelteon has few adverse effects and higher affinity for MT1 and MT2 receptors than melatonin. The aim of the present study was to determine the efficacy of ramelteon in elderly patients with delirium caused by different primary diseases/conditions.
Delirium and its prevention with melatonergic drugs. [2014]Delirium is a complex neurobehavioral syndrome caused by dysregulation of brain activity, characterized by an alteration in the level of attention and awareness, which develops over a short period of time and is seen as a change from the patient's baseline. Dysregulation of 24-hour circadian cycles, including melatonin secretion or activity, has suggested the potential therapeutic use of melatonergic drugs for delirium. Melatonin and the melatonin analog drug ramelteon have been shown to be effective in the prevention of delirium in three controlled studies. Additional studies using these drugs are warranted.
Melatonin intervention to prevent delirium in hospitalized patients: A meta-analysis. [2022]Evaluation of the effectiveness of melatonin is necessary to prevent the development of delirium in hospitalized patients. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland of the brain from the amino acid tryptophan. Synthetic melatonin supplements have been used for various medical conditions, especially sleep-related diseases, and have proved to be successful.