Critically Ill PatientsPhase 4NCT00470821
Oral Melatonin in Critically Ill High-risk Patients
A Phase 4 study testing Oral melatonin 3mg BID in people with Critically Ill Patients and Mechanically Ventilated Patients, run by University of Milan at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Critically Ill Patients, Mechanically Ventilated Patients
- What is being tested?
- Oral melatonin 3mg BID
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 1 siteItaly
- Study dates
- May 2007to May 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- High Treatment > 1 day
- Normal gastrointestinal function
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Controlled, Double Blind Trial to Evaluate Sedation and Quality of Life in High-risk, Critically Ill Patients Treated With Oral Melatonin
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.
Read the 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.
- Being tested
- Oral melatonin 3mg BID, Placebo
- Keywords
- melatonin, actigraphy, sedation, critical patients, ICU
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral melatonin 3mg BIDDrug
Also called MELATONIN 3 mg
Identical tablets containing melatonin 3 mg. Nurses are requested to give two tablets daily, at 8 PM and 12 PM
PlaceboDrug
Identical tablets without the active principles. Each evening nurses are requested to give 2 tablets at 8 PM and 12 PM
| Study group | Role | What they receive |
|---|---|---|
| A - placebo | Placebo comparator | Identical tablets without the active principles. Each evening, nurses are requested to give 2 tablets at 8 PM and 12 PM Receives: Drug: Placebo |
| B - melatonin | Active comparator | Identical tablets containing melatonin 3 mg Nurses are requested to give two tablets daily, at 8 PM and 12 PM. Receives: Drug: Oral melatonin 3mg BID |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall sedatives daily doses
Measured: Discharge from ICU
Secondary outcomes (6)
Prevalence of Delirium assessed with CAM-ICU
Measured: Discharge from ICU
Prevalence of mental disorders
Measured: 60 days after ICU discharge
ICU length of stay
Measured: Discharge from ICU
ICU mortality
Measured: Discharge from ICU
Hospital mortality
Measured: Hospital discharge
Sleep quantity assessed by wrist actigraphy
Measured: Discharge from ICU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2007 (estimated)
- Study startMay 2007
- Primary completionApr 2010
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critically Ill PatientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milan
- Sponsor type
- University, hospital or other
- Investigators
- Gaetano Iapichino, MD, Study chair, University of Milan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00470821
- Sponsor's protocol ID
- Mela-UniMi-0001
- Status last verified
- Jan 2010
- First submitted
- 4 May 2007
- Last updated
- 28 Jul 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled, Double Blind Trial to Evaluate Sedation and Quality of Life in High-risk, Critically Ill Patients Treated With Oral Melatonin
- ClinicalTrials.gov ID
- NCT00470821
- Acronym / sponsor ID
- Mela-UniMi-0001
- Keywords
- melatonin, actigraphy, sedation, critical patients, ICU
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- University of MilanUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- Apr 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 8 May 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A - placebo | Placebo comparator | Drug: PlaceboIdentical tablets without the active principles. Each evening, nurses are requested to give 2 tablets at 8 PM and 12 PM |
| B - melatonin | Active comparator | Drug: Oral melatonin 3mg BIDIdentical tablets containing melatonin 3 mg Nurses are requested to give two tablets daily, at 8 PM and 12 PM. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- High Treatment > 1 day
- Normal gastrointestinal function
Key exclusion criteria (6 listed)
- 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, ...)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral melatonin 3mg BIDAlso: MELATONIN 3 mgIdentical tablets containing melatonin 3 mg. Nurses are requested to give two tablets daily, at 8 PM and 12 PM | Drug | B - melatonin |
| PlaceboIdentical tablets without the active principles. Each evening nurses are requested to give 2 tablets at 8 PM and 12 PM | Drug | A - placebo |
Primary outcome
Overall sedatives daily doses
Time frame: Discharge from ICU
6 secondary outcomes
Prevalence of Delirium assessed with CAM-ICU
Time frame: Discharge from ICU
Prevalence of mental disorders
Time frame: 60 days after ICU discharge
ICU length of stay
Time frame: Discharge from ICU
ICU mortality
Time frame: Discharge from ICU
Hospital mortality
Time frame: Hospital discharge
Sleep quantity assessed by wrist actigraphy
Time frame: Discharge from ICU
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gaetano Iapichino, MD study chair
University of Milan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oral melatonin 3mg BID in people with Critically Ill Patients and Mechanically Ventilated Patients, run by University of Milan at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall sedatives daily doses (time frame: Discharge from ICU). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2010.