MIND After Surgery

NCT ID: NCT03785158

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-14
• Study Completion Date: 2025-07-05

Brief Summary

Delirium is the most common neurological adverse outcome in elderly surgical patients. It is associated with an increased mortality and morbidity, including need for prolonged hospital stay and institutional care. Despite this, there are no effective preventive strategies. Melatonin is a hormone released from the pineal gland. It is used to improve sleep quality and to treat jet lag. Small studies have suggested that it can decrease the chances of delirium. Since the existing literature is small and uncertain, it is important to test its benefit in a large sample to help guide clinicians. This proposed trial is aimed at testing assessing the feasibility of a large, multi-center, randomized control trial to decrease the incidence of postoperative delirium.

Detailed Description

Delirium is defined as an acute and fluctuating disturbance in cognition characterized by alterations in the level of attention and awareness, which develops over a relative short period of time and represents a change from the subject's baseline. Its incidence increases with age and occurs in nearly 50% of elderly inpatients. Postoperative delirium (POD) increases the risk of patient morbidity and mortality and thereby increasing the cost for the health care system. Increased risk of mortality persists even three years after hospitalization, and is an independent risk factor for urinary incontinence, falls, and decubitus ulcers.

A large prospective study of 1341 patients having non-cardiac surgery with a postoperative stay of at least 48 hours, reported an overall incidence of 9% in >50 years and 15% in >70 years. Another recent study involving 566 patients of similar surgical cohort reported an incidence of 24%.

With no current effective treatment, there is a greater focus on prevention of delirium. Approximately 15% of all POD could be preventable. Preventive strategies can be pharmacological and non-pharmacological. Non-pharmacological strategies are multifaceted and involve different interventions. Among attempted pharmacological options, none have really shown much promise and many suffer from associated adverse effects.

Melatonin is a pineal gland hormone that regulates the sleep-wake rhythm. Disruption of the sleep-wake cycle is observed in delirium. Abnormal tryptophan metabolism is hypothesized as a cause for delirium and melatonin supplementation is observed to decrease the breakdown of tryptophan and serotonin through positive feedback. In patients who develop POD, low tryptophan and serum melatonin levels were observed. Other advantages of melatonin, being a natural supplement, include improved sleep, sparing of sedatives, minimal potential for abuse, or hangover effects.

Systematic reviews done with the existing literature specific to melatonin by a literature search of MEDLINE, EMBASE and Cochrane databases for combination of terms "melatonin" and "delirium", restricted to clinical trials and up to October 25, 2017 found one relevant systematic review: this systematic review looked at the use of melatonin for delirium prevention and found four randomized control trials (RCT), out of which three showed positive results and one showed a negative result. Presently, despite its potential to reduce POD and improve sleep, the role of melatonin in the elderly surgical population is uncertain. There is a clear need for a large, well-designed study to establish definitive evidence.

Conditions

Post-operative Delirium; Major Non-cardiac Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Melatonin

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 Type: ACTIVE_COMPARATOR

Liquid Melatonin

Intervention Type: OTHER

Melatonin is a natural supplement.

Placebo Group

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Similar looking/tasting placebo syrup

Interventions

Liquid Melatonin

Melatonin is a natural supplement.

Intervention Type: OTHER

Placebo

Similar looking/tasting placebo syrup

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age >65 years
• having a major non-cardiac surgery (which involve major vascular, thoracic, orthopedic, gynecological, otolaryngeal, general and gastrointestinal surgeries) with an expected hospital stay of 2 days or more, and
• ability to provide informed consent

Exclusion Criteria

• active delirium or dementia
• ongoing melatonin treatment
• unable to take oral medications
• planned postoperative ventilation
• previous study participation
• allergy to melatonin
• hepatic impairment defined as alanine aminotransferase greater than 500 IU/L
• previous liver transplant or liver cirrhosis of Child-Pugh classes B and C
• not willing to participate
• language barrier

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Joseph's Healthcare Hamilton

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Hamilton Health Sciences-Juravinski Hospital Location

Hamilton, Ontario, Canada

Countries

Canada

Other Identifiers

5506

Identifier Type: -

Identifier Source: org_study_id