Exogenous Melatonin in Intensive Care Unit Chronodisruption

NCT03708341 | Recruiting Phase 3 DMC

• 1 other identifier: LPCQM/07/17
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

To this day, a small number of studies have evaluated the effect of melatonin on the modifications of the characteristics of sleep in critical care units, with mostly a small studied population. However, no study has been realized on a large population, nor has it evaluated the association between genetic factors and response to treatment (melatonin), hence the originality of our study. In our study we hypothesized that systematic melatonin usage in ICU can ameliorate the total sleep time and the fragmentation index and can decrease the confusion related to sleep deprivation.

Conditions

Sleep Deprivation; Intensive Care Psychosis

Keywords

melatonin; Sleep Deprivation; Intensive Care Psychosis

Outcome Measures

Primary Outcomes (1)

• Total sleep time

  total time spent sleeping in ICU (in minutes)

  14 days or ICU discharge, whichever came first

Secondary Outcomes (7)

• REM sleep latency

  14 days or ICU discharge, whichever came first

• Fragmentation index

  14 days or ICU discharge, whichever came first

• Sleep efficacy

  14 days or ICU discharge, whichever came first

• Incidence of delirium in ICU

  14 days or ICU discharge, whichever came first

• Degree of agitation of patients

  14 days or ICU discharge, whichever came first

Study Arms (2)

Melatonin

EXPERIMENTAL

Patients will be administered melatonin 5 mg at a fixed time every day during their ICU stay (from day of admission till day of discharge from ICU)

Drug: Melatonin 5 mg

Placebo

PLACEBO COMPARATOR

Patients will be administered a placebo pill that is identical in shape and color to the melatonin pill, at a fixed time every day during their ICU stay

Drug: Placebo Oral Tablet

Interventions

Melatonin 5 mg DRUG

Systematic daily administration of melatonin 5 mg during patient's ICU stay

Melatonin

Placebo Oral Tablet DRUG

Systematic daily administration of placebo during patient's ICU stay

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients or their parents who have signed an informed consent allowing us to exploit and analyse their clinical, biological and pharmacological data (see Appendix 1)
• Patients staying more than 48 hours in ICU (acute ICU confusion occurs in the 48-72h following admission)
• Drugs affecting sleep architecture (co-variables):
• Opiates: increase N2, decrease REM
• NSAIDs: reduce sleep efficacy, increase arousal
• Beta blockers: insomnia, REM sleep disappearance
• Corticosteroids (varies according to half life and dose): REM sleep disappearance, induce awakening, stimulant effect
• Haloperidol: increases sleep efficacy, increases N2 duration
• Respiratory assistance: ventilated patients v/s non ventilated patients (co-variables)
• Patients presenting with delirium or sleep disorders at admission will not be excluded, but a note will be taken on the baseline case report form (CRF)

You may not qualify if:

• Patients less than 18 years old
• Patients with central neurological disease: post traumatic patients, Parkinson disease, patients presenting with CVA, patients with neurodegenerative diseases, etc.
• Patients taking drugs capable of altering or inducing delirium:
• Atypical antipsychotics (olanzapine, risperidone, etc.), which increase sleep efficacy, total sleep time, and NREM sleep, and reduce prevalence of ICU psychosis
• BZD-like drugs (zolpidem, zopiclone) which induce delirium
• Melatonin allergy
• Any disorders capable of altering oral melatonin absorption (e.g. intestinal occlusion)
• Predicted ICU stay of less than 24 hours (e.g. post surgical monitoring)

Sponsors & Collaborators

• Saint-Joseph University: lead

Study Sites (1)

Hotel Dieu de France

Beirut, Lebanon

RECRUITING

Related Publications (7)

• Knauert MP, Malik V, Kamdar BB. Sleep and sleep disordered breathing in hospitalized patients. Semin Respir Crit Care Med. 2014 Oct;35(5):582-92. doi: 10.1055/s-0034-1390080. Epub 2014 Oct 29.

  PMID: 25353103 BACKGROUND

• Gandhi AV, Mosser EA, Oikonomou G, Prober DA. Melatonin is required for the circadian regulation of sleep. Neuron. 2015 Mar 18;85(6):1193-9. doi: 10.1016/j.neuron.2015.02.016. Epub 2015 Mar 5.

  PMID: 25754820 BACKGROUND

• Gabor JY, Cooper AB, Crombach SA, Lee B, Kadikar N, Bettger HE, Hanly PJ. Contribution of the intensive care unit environment to sleep disruption in mechanically ventilated patients and healthy subjects. Am J Respir Crit Care Med. 2003 Mar 1;167(5):708-15. doi: 10.1164/rccm.2201090.

  PMID: 12598213 BACKGROUND

• Pisani MA, Friese RS, Gehlbach BK, Schwab RJ, Weinhouse GL, Jones SF. Sleep in the intensive care unit. Am J Respir Crit Care Med. 2015 Apr 1;191(7):731-8. doi: 10.1164/rccm.201411-2099CI.

  PMID: 25594808 BACKGROUND

• Jones CR, Huang AL, Ptacek LJ, Fu YH. Genetic basis of human circadian rhythm disorders. Exp Neurol. 2013 May;243:28-33. doi: 10.1016/j.expneurol.2012.07.012. Epub 2012 Jul 28.

  PMID: 22849821 BACKGROUND

• Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001 Dec 5;286(21):2703-10. doi: 10.1001/jama.286.21.2703.

  PMID: 11730446 BACKGROUND

• Huang H, Jiang L, Shen L, Zhang G, Zhu B, Cheng J, Xi X. Impact of oral melatonin on critically ill adult patients with ICU sleep deprivation: study protocol for a randomized controlled trial. Trials. 2014 Aug 18;15:327. doi: 10.1186/1745-6215-15-327.

  PMID: 25135124 BACKGROUND

MeSH Terms

Conditions

Sleep Deprivation

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Moussa A Riachy, MD

CONTACT

+9613361672; moussariachy@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo, double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Controled Trial. GLMM will be used to analyze the data due to its ability to handle non-normal distributions and account for both fixed and random effects.

Study Record Dates

• First Submitted: September 26, 2018
• First Posted: October 17, 2018
• Study Start: November 15, 2018
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: February 14, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)