Melatonin for Delirium

(MIND Trial)

Recruiting at 1 trial location

Overseen By Harsha Shanthanna, MD

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Must not be taking: Melatonin

Disqualifiers: Delirium, Dementia, Hepatic impairment, others

Compensation: Varies

Number of Visits: Unknown

Duration: 8 days

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test if melatonin, a natural sleep hormone, can prevent delirium in elderly surgical patients. Delirium is a common and serious issue for these patients, and melatonin might help by improving their sleep. Melatonin is a hormone produced by the pineal gland and has been used successfully for various medical conditions, especially sleep-related diseases.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are already taking melatonin, you cannot participate in the trial.

Is melatonin safe for use in humans?

Melatonin is a naturally occurring hormone that is considered safe and has been used in studies to improve sleep and prevent delirium, with no major safety concerns reported. ^{1 2 3 4 5}

How does melatonin differ from other drugs for delirium?

Melatonin is unique because it is a natural hormone that helps regulate sleep, and it is being explored for its potential to prevent delirium, especially in older adults and critically ill patients, by improving sleep and stabilizing the day-night cycle. Unlike other treatments, there is currently no standard drug that effectively prevents delirium, making melatonin a novel option in this area. ^{1 2 3 4 6}

What data supports the effectiveness of the drug Liquid Melatonin for treating delirium?

Research suggests that melatonin can help prevent delirium in non-critically ill surgical and medical patients, and it may also improve sleep quality in ICU patients, which is important because poor sleep can contribute to delirium. ^{1 2 3 7 8}

Are You a Good Fit for This Trial?

This trial is for people over 65 who are having major non-cardiac surgery and will stay in the hospital for at least two days. They must be able to agree to the study themselves. It's not for those with active delirium or dementia, current melatonin use, trouble taking pills by mouth, planned breathing support after surgery, past study participation, melatonin allergy, severe liver problems, language barriers or unwillingness to participate.

Inclusion Criteria

I am older than 65 years.

Ability to provide informed consent

I am scheduled for a major surgery that is not heart-related and will be in the hospital for at least 2 days.

Exclusion Criteria

I cannot take medications by mouth.

I am not willing to participate in the trial.

My liver enzyme (ALT) level is above 500 IU/L.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3 mg of liquid melatonin or placebo by oral route for 8 days, starting 1-2 hours prior to surgery and continuing with bedtime doses until discharge or for the first 7 days.

8 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive status and incidence of delirium.

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Liquid Melatonin
• Placebo

Trial Overview The MIND After Surgery trial is testing if liquid melatonin can prevent delirium in elderly patients after surgery compared to a placebo (a substance with no active drug). Participants are randomly chosen to receive either melatonin or placebo to see if there's a difference in how often they experience confusion and memory problems post-surgery.

How Is the Trial Designed?

Group I: Melatonin Active Control 1 Intervention

3 mg of liquid melatonin by oral route for 8 days. The 1st dose will be given 1-2 hours prior to the surgery, followed by bed time doses (between 7-9 pm) given on postoperative day (POD) 1 until discharge or for the first 7 days.

Group II: Placebo Group Placebo Group 1 Intervention

Similar looking/tasting 3 mg (5 ml) placebo syrup administered preoperatively by oral route and for the next 7 days or until discharge. The 1st dose will be given 1-2 hours prior to the surgery, followed by bed time doses (between 7-9 pm) given on postoperative day (POD) 1 until discharge or for the first 7 days.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

St. Joseph's Healthcare Hamilton

Collaborator

Trials

203

Recruited

26,900+

Published Research Related to This Trial

A review of six clinical trials on melatonin receptor agonists for preventing delirium showed mixed results, with some trials indicating a reduction in delirium incidence by 12% to 30%, while the largest trial found no benefit.

Due to the conflicting evidence and limited safety evaluations, the routine use of melatonin receptor agonists for delirium prevention is not currently recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin Receptor Agonists for Delirium Prevention. Walker, CK., Gales, MA.[2022]

Melatonin and its agonist ramelteon may effectively reduce the duration of delirium in hospitalized patients, with a meta-analysis showing a significant decrease of about 1.72 days compared to placebo across three randomized controlled trials involving 1211 participants.

Despite these promising results, the overall quality and quantity of the current studies are limited, suggesting that clinicians should await more robust data from ongoing trials before widely recommending melatonin for delirium treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin and Ramelteon for the treatment of delirium: A systematic review and meta-analysis. Beaucage-Charron, J., Rinfret, J., Coveney, R., et al.[2023]

Melatonin and its analog ramelteon have shown effectiveness in preventing delirium, as demonstrated in three controlled studies, suggesting their potential as therapeutic options.

Delirium is linked to disruptions in brain activity and circadian rhythms, indicating that melatonergic drugs may help restore normal brain function and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delirium and its prevention with melatonergic drugs. Howland, RH.[2014]

Melatonin may help prevent and manage delirium in elderly patients, as suggested by two randomized controlled trials, although it does not reduce the severity of delirium or improve behaviors and functions.

Ramelteon, a melatonin agonist, showed benefits in preventing delirium in medically ill older adults compared to placebo, and both melatonin and ramelteon were well tolerated in the studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin and melatonin agonist for delirium in the elderly patients. Chakraborti, D., Tampi, DJ., Tampi, RR.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Feasibility of melatonin for prevention of delirium in critically ill patients: a protocol for a multicentre, randomised, placebo-controlled study. [2022]

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

Melatonin Receptor Agonists for Delirium Prevention. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Melatonin and Ramelteon for the treatment of delirium: A systematic review and meta-analysis. [2023]

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

The Effects of Melatonin Supplementation on Sleep Quality and Assessment of the Serum Melatonin in ICU Patients: A Randomized Controlled Trial. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Melatonin intervention to prevent delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Prophylactic Melatonin for Delirium in Intensive Care (Pro-MEDIC): study protocol for a randomised controlled trial. [2022]

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

Delirium and its prevention with melatonergic drugs. [2014]

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

Melatonin and melatonin agonist for delirium in the elderly patients. [2022]