Oral Melatonin in Critically Ill High-risk Patients

NCT ID: NCT00470821

Last Updated: 2010-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2010-05-31

Brief Summary

Sleep disruptions are extremely common in high-risk critically ill patients. The investigators want to analyse oral melatonin potentialities as a sedative and a free-radicals scavenger for critically ill patients, and secondarily for preventing Delirium during their ICU stay and post-traumatic stress disorders after ICU discharge.

Detailed Description

The physiological secretion of such melatonin follows a circadian rhythm: melatonin plasma concentration increases with the dark reaching a peak around to midnight and then gradually decreases (Reiter, 1996; Shigeta et al., 2001; Kunz et al., 2004; Brzezinski et al., 2005).

Administration of oral melatonin could be useful in critically ill high-risk patients in Intensive Care Units because these patients are often suffering from sleep disturbances (Weber et al., 1985; Bourne and Mills, 2004) possibly because of:

• presence of underlying pathology with pain and anxiety,
• presence of oral or nasal respiratory prosthesis,
• execution of therapeutic procedures on 24 h. Moreover it has been demonstrated that in ICU patients melatonin rhythm is desynchronized (Bourne and Mills, 2000). This is probably related to sedation and-or mechanical ventilation. Furthermore, it has been showed that melatonin is a powerful anti-oxidant, therefore it could be potentially useful in critical patients usually characterized by increased production of oxygen free radicals.

AIM OF THE STUDY The study is aimed to estimate if the administration of oral melatonin in ICU patients is able to regularize the sleep-waking rhythm, improving sleep quality and reducing episodes of agitation/mental confusion. The main objectives are: assessment of sleep quality, prevalence of mental confusion/agitation, amount of daily sedative drugs administered and modification of redox status.

ENROLLMENT OF PATIENTS At the admission in ICU, obtained the informed consent, the patients will be randomly assigned to the "Treatment" group receiving melatonin 3mg BID by oral route (or nasogastric tube) or to the "Control" group receiving placebo. The sedation will be performed according to clinical standard.

EXPERIMENTAL PROTOCOLS

The following parameters will be monitored:

• epidemiological data,
• quality of the sleep estimated by wrist actigraphy,
• EEG profile on 24h in order to estimate the distribution of sleep phases,
• diurnal and nocturnal hours of sleep,
• total amount of sedative drugs during 24 hours, particularly during nocturnal sedation,
• assessment of sedation level (RASS) (Sessler et al., 2002; Ely et al., 2003),
• episodes of psychomotor agitation and mental confusion (CAM-ICU) (Ely, 2001; 2004),
• evaluation of blood redox state (GSH, GSSG, GSH/GSSG),
• adverse events.

AT THE DISCHARGE FROM ICU, evaluation of:

• SCID-I and SCID-II (Structured Clinical Interview for DSM),
• CAPS (Clinician Administered PTSD Scales),
• HAM-A and HAM-D (Hamilton Rating Scales for Anxiety and for Depression),
• completion of the module for the stressors in ICU and for the transcription of the dreams.

3 MONTHS AFTER DISCHARGE FROM ICU, evaluation of:

• SCID-I and II,
• CAPS,
• HAM-A and HAM-D,
• TAT (Thematic Apperception Test),
• completion of the module for the stressors in ICU and for the transcription of the dreams.

Conditions

Critically Ill Patients; Mechanically Ventilated Patients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

A - placebo

Identical tablets without the active principles. Each evening, nurses are requested to give 2 tablets at 8 PM and 12 PM

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Identical tablets without the active principles. Each evening nurses are requested to give 2 tablets at 8 PM and 12 PM

B - melatonin

Identical tablets containing melatonin 3 mg Nurses are requested to give two tablets daily, at 8 PM and 12 PM.

Group Type: ACTIVE_COMPARATOR

Oral melatonin 3mg BID

Intervention Type: DRUG

Identical tablets containing melatonin 3 mg. Nurses are requested to give two tablets daily, at 8 PM and 12 PM

Interventions

Oral melatonin 3mg BID

Identical tablets containing melatonin 3 mg. Nurses are requested to give two tablets daily, at 8 PM and 12 PM

Intervention Type: DRUG

Placebo

Identical tablets without the active principles. Each evening nurses are requested to give 2 tablets at 8 PM and 12 PM

Intervention Type: DRUG

Other Intervention Names

MELATONIN 3 mg

Eligibility Criteria

Inclusion Criteria

• High Treatment > 1 day
• Normal gastrointestinal function

Exclusion Criteria

• Status asthmaticus
• Chronic renal failure under dialytic treatment
• Severe hepatopathy (Child-Pugh class = C)
• Comatous patients (GCS < 12)
• Head trauma, severe neurological diseases (ictus cerebri, SAH, ...)
• Intoxicated patients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Milan

OTHER

Sponsor Role: lead

Responsible Party

Istituto di Anestesiologia e Rianimazione, Università di Milano

Principal Investigators

Gaetano Iapichino, MD

Role: STUDY_CHAIR

University of Milan

Locations

Azienda Ospedaliera San Paolo - Polo Universitario

Milan, , Italy

Countries

Italy

Other Identifiers

Mela-UniMi-0001

Identifier Type: -

Identifier Source: org_study_id