The Use of Melatonin for Delirium Prevention in Medically Hospitalized Patients

NCT06509191 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: Sultan Qaboos University
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 2

Brief Summary

The high prevalence of delirium in hospitalized older adults, with significant associated morbidity and mortality, emphasize the need for effective prevention strategies. Limited trials have explored melatonin's potential in preventing delirium among patients admitted to general medical wards. Previous trials on melatonin's preventive role in medical wards had limitations, necessitating a robust, double-blinded, placebo-controlled design with a larger sample size. This randomized, double-blind study of melatonin versus placebo aims to investigate the efficacy of melatonin, a neurohormone regulating the sleep-wake cycle, in preventing delirium among medically hospitalized patients aged 65 or older. Given the high prevalence of delirium in this population and its association with adverse outcomes, the study seeks to contribute valuable insights into an effective preventive strategy.

Conditions

Delirium

Keywords

delirium; melatonin; Hospitalized; Medical

Outcome Measures

Primary Outcomes (1)

• Incidence of delirium

  Incidence of delirium development during hospitalisation using the 3-Minute Diagnostic Confusion Assessment Method (3D-CAM).

  5 days

Secondary Outcomes (10)

• Onset time of delirium

  5 days

• Duration of delirium during hospitalization

  5 days

• Sleep pattern and night awakenings

  5 days

• Days utilizing physical restraints.

  5 days

• • Number of rescue medications during hospitalization.

  5 days

Study Arms (3)

Melatonin 5mg/day

EXPERIMENTAL

Intervention group 1: Melatonin 5mg/day * Study drug will be given at 20:00 - 22:00 daily, starting on the day of enrolment until discharge, death, or up to 5 days as most medically hospitalised patients at great risk of delirium in the first few days of admission.(20) * The study medication will be given by mouth or if needed, via the feeding tube followed by a flush with 20mL water.

Drug: Intervention 1

Melatonin 8 mg/day

EXPERIMENTAL

Intervention group 2:Study drug will be given at 20:00 - 22:00 daily, starting on the day of enrolment until discharge, death, or up to 5 days as most medically hospitalised patients at great risk of delirium in the first few days of admission.(20) • The study medication will be given by mouth or if needed, via the feeding tube followed by a flush with 20mL water.

Drug: Intervention 2

Placebo

PLACEBO COMPARATOR

* Study drug will be given at 20:00 - 22:00 daily, starting on the day of enrolment until discharge, death, or up to 5 days as most medically hospitalised patients at great risk of delirium in the first few days of admission. (20) * The study medication will be given by mouth or if needed, via the feeding tube followed by a flush with 20mL water.

Other: Control

Interventions

Intervention 1 DRUG

Melatonin 5mg/day

Melatonin 5mg/day

Intervention 2 DRUG

Melatonin 8 mg/day

Melatonin 8 mg/day

Control OTHER

Placebo

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Patient aged 65 years and above acutely admitted under the care of General Internal Medicine Unit

You may not qualify if:

• Patients admitted to the ward, however meeting requirement for vasopressors or non-invasive ventilation.
• Patient admitted through emergency to Intensive Care Unit (ICU) or High Dependency Unit (HDU).
• Aphasic patients.
• Patients with language barriers.
• Already taking melatonin or ramelteon at the time of randomization.
• Presence of delirium at the time of randomization.
• If enteral medications are contraindicated due to gastrointestinal conditions.
• If enteral medications are not allowed due to unavailability of nasogastric tube
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (liver function tests) \> 3 times the upper limit of normal.
• Patient on strong cytochrome P450 1A2 (CYP1A2) inhibitors (namely: fluvoxamine and viloxazine) .
• Patient with active alcohol drinking or admitted with alcohol withdrawal syndrome.
• Subject or proxy unable to provide informed consent within 24 hours of admission.
• Patients with the following autoimmune diseases (Rheumatoid arthritis, inflammatory bowel disease and systemic lupus erythematosus).
• Allergy to melatonin.

Sponsors & Collaborators

• Sultan Qaboos University: lead

Study Sites (2)

Sultan Qaboos University Hospital

Muscat, 123, Oman

NOT YET RECRUITING

Sultan Qaboos University Hospital

Muscat, 123, Oman

RECRUITING

Related Publications (11)

• Riviere J, van der Mast RC, Vandenberghe J, Van Den Eede F. Efficacy and Tolerability of Atypical Antipsychotics in the Treatment of Delirium: A Systematic Review of the Literature. Psychosomatics. 2019 Jan-Feb;60(1):18-26. doi: 10.1016/j.psym.2018.05.011. Epub 2018 May 31.

  PMID: 30181002 BACKGROUND

• Shen YZ, Peng K, Zhang J, Meng XW, Ji FH. Effects of Haloperidol on Delirium in Adult Patients: A Systematic Review and Meta-Analysis. Med Princ Pract. 2018;27(3):250-259. doi: 10.1159/000488243. Epub 2018 Mar 8.

  PMID: 29518791 BACKGROUND

• Burton JK, Craig LE, Yong SQ, Siddiqi N, Teale EA, Woodhouse R, Barugh AJ, Shepherd AM, Brunton A, Freeman SC, Sutton AJ, Quinn TJ. Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. 2021 Jul 19;7(7):CD013307. doi: 10.1002/14651858.CD013307.pub2.

  PMID: 34280303 BACKGROUND

• Al Huraizi AR, Al-Maqbali JS, Al Farsi RS, Al Zeedy K, Al-Saadi T, Al-Hamadani N, Al Alawi AM. Delirium and Its Association with Short- and Long-Term Health Outcomes in Medically Admitted Patients: A Prospective Study. J Clin Med. 2023 Aug 17;12(16):5346. doi: 10.3390/jcm12165346.

  PMID: 37629388 BACKGROUND

• Goldberg TE, Chen C, Wang Y, Jung E, Swanson A, Ing C, Garcia PS, Whittington RA, Moitra V. Association of Delirium With Long-term Cognitive Decline: A Meta-analysis. JAMA Neurol. 2020 Nov 1;77(11):1373-1381. doi: 10.1001/jamaneurol.2020.2273.

  PMID: 32658246 BACKGROUND

• Lozano-Vicario L, Garcia-Hermoso A, Cedeno-Veloz BA, Fernandez-Irigoyen J, Santamaria E, Romero-Ortuno R, Zambom-Ferraresi F, Saez de Asteasu ML, Munoz-Vazquez AJ, Izquierdo M, Martinez-Velilla N. Biomarkers of delirium risk in older adults: a systematic review and meta-analysis. Front Aging Neurosci. 2023 May 12;15:1174644. doi: 10.3389/fnagi.2023.1174644. eCollection 2023.

  PMID: 37251808 BACKGROUND

• Wang CG, Qin YF, Wan X, Song LC, Li ZJ, Li H. Incidence and risk factors of postoperative delirium in the elderly patients with hip fracture. J Orthop Surg Res. 2018 Jul 27;13(1):186. doi: 10.1186/s13018-018-0897-8.

  PMID: 30049276 BACKGROUND

• Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22. doi: 10.1016/S0140-6736(13)60688-1. Epub 2013 Aug 28.

  PMID: 23992774 BACKGROUND

• Chin YC, Koh GC, Tay YK, Tan CH, Merchant RA. Underdiagnosis of delirium on admission and prediction of patients who will develop delirium during their inpatient stay: a pilot study. Singapore Med J. 2016 Jan;57(1):18-21. doi: 10.11622/smedj.2016007.

  PMID: 26831312 BACKGROUND

• Al Alawi AM, Al Busaidi S, Al Rasbi SK, Al Farsi RS, Al Zeedy K, Al Huraizi AR, Al-Maqbali JS. Effect of melatonin versus placebo for the prevention of delirium among medically hospitalised older patients: a double-blinded randomised controlled trial (project RESTORE). BMJ Open. 2026 Jan 27;16(1):e107775. doi: 10.1136/bmjopen-2025-107775.

  PMID: 41592826 DERIVED

• Al-Maqbali JS, Al-Busaidi S, Al Farsi RS, Al Rasbi S, Al Zeedy K, Al Huraizi AR, Al Alawi AM. Effect of melatonin versus placebo for prevention of delirium among medically hospitalised patients: study protocol for a single-centre, double-blinded, randomised controlled trial (project RESTORE). BMJ Open. 2025 Feb 25;15(2):e094195. doi: 10.1136/bmjopen-2024-094195.

  PMID: 40000080 DERIVED

MeSH Terms

Conditions

Delirium

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Abdullah M Al Alawi, FRACP

CONTACT

+96895384990; dr.abdullahalalawi@gmail.com

Juhaina Salim Al Maqbali, MSc

CONTACT

juhaina@squ.edu.om

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sr. Consultant

Model Details: The study will be a randomized, double-blind, and parallel arm placebo-controlled trial which will take place at Sultan Qaboos University Hospital. All patients aged 65 years and over admitted through emergency department to General Internal Medical Units will be screen for eligibility.

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 19, 2024
• Study Start: September 30, 2024
• Primary Completion: March 1, 2025
• Study Completion: June 1, 2025
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: upon completion of the data analysis
• Access Criteria: The de-identified IPD will be made available to researchers upon reasonable request

Locations

OM (2)