Melatonin for Delirium

(MIND Trial)

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether melatonin, a hormone that aids sleep, can reduce the risk of delirium (a serious state of confusion) after surgery in older patients. Participants will receive either liquid melatonin or a placebo (a dummy treatment) to determine melatonin's effectiveness. Those planning major surgery, such as orthopedic or general surgery, with a hospital stay of at least two days, may find this trial suitable. As an unphased trial, it offers a unique opportunity to contribute to understanding how melatonin might improve post-surgery outcomes.

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

Research has shown that melatonin is generally safe for use, but its effectiveness in reducing delirium remains uncertain. One study found that a 4 mg dose was safe but did not affect delirium rates. Another study with a 3 mg dose also confirmed its safety, yet it did not reduce delirium cases in hospitalized patients. These studies suggest that melatonin is well-tolerated, but further research is needed to determine its potential in preventing delirium. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for delirium?

Unlike the standard treatments for delirium, which often involve antipsychotics or sedatives, this approach uses melatonin, a hormone naturally found in the body. Researchers are excited about melatonin because it has a unique action of regulating sleep-wake cycles, which could help stabilize the disturbed sleep patterns often seen in delirium. Additionally, melatonin is known for having a favorable safety profile and fewer side effects compared to traditional medications. This makes it a promising option for patients who might be sensitive to harsher drugs.

What evidence suggests that melatonin might be an effective treatment for delirium?

Research suggests that melatonin might help lower the risk of post-surgery confusion, known as delirium. Some small studies show that melatonin can reduce the chances of experiencing delirium, especially after surgery. However, larger studies have not always found significant differences. For instance, one study found little difference in the number of delirium-free days between those taking melatonin and those taking a placebo. In this trial, participants will receive either melatonin or a placebo to further investigate these effects. Another study suggested that a lower dose of melatonin might be more effective than a higher dose. More research is needed to confirm these findings. ^{2 3 4 6 7}

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

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11587658/

Effects of melatonin on the prevention of delirium in ... The data indicate that melatonin may reduce the incidence of delirium, particularly in postoperative patients. However, further studies are ...

2. thebottomline.org.uk thebottomline.org.uk/summaries/icm/pro-medic/

Pro-MEDIC Outcome · Comparing melatonin vs placebo · No significant difference in. Average percentage of delirium free days: 79.5% vs. 80.2%; Average ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40608082/

Melatonin for prevention of delirium in patients receiving ... This randomized clinical trial found that the low-dose of melatonin (0.3 mg nightly) achieved a better pharmacokinetic profile than the high-dose (3 mg nightly ...

4. link.springer.com link.springer.com/article/10.1007/s00134-022-06656-7

Melatonin in ICU delirium: hormone of darkness Patients aged ≥ 18 years with expected ICU stay of ≥ 72 h were randomized to enteral liquid melatonin 4 mg or matched placebo qHS until ICU ...

5. mdpi.com mdpi.com/2077-0383/12/2/435

Melatonin or Ramelteon for Delirium Prevention in ICU Melatonin and ramelteon do not seem to reduce delirium incidence in ICU patients but evidence is weak. More studies are needed to confirm this finding.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35220473/

Prophylactic melatonin for delirium in intensive care (Pro- ... Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06509191

The Use of Melatonin for Delirium Prevention in Medically ... The study concluded that the nightly use of 3 mg melatonin did not reduce the incidence of delirium. 29 Overall, the trial conducted on hospitalized patients in ...