Clinical trial NCT03785158: MIND After Surgery
Official title: Melatonin for Preventing Postoperative Delirium in Elderly Patients; a Multi-centre Randomized Placebo Controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Post-operative Delirium
Major Non-cardiac Surgery
Keywords: Delirium
Elderly patients having non-cardiac surgery
Melatonin
sleep quality
sleep deprivation
sleep-wake cycle
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: St. Joseph's Healthcare Hamilton
First posted: 2018-12-24
Enrollment: 88
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomised, placebo-controlled, two arm parallel design pilot RCT
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Recruitment rate
timeFrame: 6 months
measure: Medication compliance
timeFrame: 8 days
measure: Follow up to 3 months
timeFrame: 3 months
measure: Proportion of patients recruited from screening
timeFrame: 6 months
Secondary outcomes:
measure: Incidence of Delirium
timeFrame: 8 days
measure: Severity of Delirium
timeFrame: 8 days
measure: Sleep quality
timeFrame: 8 days
measure: Incidence of ICU care
timeFrame: 8 days
measure: Prolonged hospital stay
timeFrame: 8 days
measure: Institutional discharge
timeFrame: 3 months
measure: Cognitive Status
timeFrame: 3 months
measure: Mortality
timeFrame: 3 months
measure: Adverse effects
timeFrame: 7 days
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton Health Sciences-Juravinski Hospital Location
state: Ontario
Study officials:
References: