DeliriumPhase 4NCT02903901
Melatonin for Prevention of Post- Operative Delirium Pilot Study Protocol
A Phase 4 study testing Melatonin in people with Delirium, run by Loyola University at 1 site in United States.
Trial summary
To test the efficacy of melatonin compared to placebo in preventing post-operative delirium and reduction in intensity or duration of delirium in individuals 65 years of age and older who undergo orthopedic surgery after low energy lower extremity fractures (LELEF). Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Delirium
- What is being tested?
- Melatonin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Jun 2018
- 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 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Patients 65 years of age and older undergoing Low Energy Lower Extremity Fractures (LELEF) surgery
- Presence of an LELEF fracture
- Low Energy (e.g., falls from standing height, falls from sitting, etc.).
- Operative Fractures:
- Pathologic femur and tibia fractures
- Femoral neck fractures
Show all 15Show fewer
- Pertroch: including intertroch, subtroch fractures
- Femoral shaft
- Supracondylar femur fractures
- Periprosthetic fractures around total hip and total knee arthroplasties
- Tibial plateau fractures
- Proximal Tibia Fractures
- Tibial Shaft Fractures
- Distal 1/3 tibia fractures
- Ankle Fractures that are admitted
Who cannot join
- Patients with previous adverse reaction or side-effects to melatonin
- Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
- Inability to communicate in English
- Patients with a Montreal Cognitive Assessment (MoCA) score of below 7 will not be included in the study because of their inability to give informed consent at that stage. This score is approximately 2 standard deviation below average score for Alzheimer's Dementia.
- Participants who are unable to give consent or communicate well in English will not be enrolled
Trial locations and contacts
1 site in 1 country.
United States1 site
Loyola University Medical Center
Maywood, Illinois, 60153
About this study
To test the efficacy of melatonin compared to placebo in preventing post-operative delirium and reduction in intensity or duration of delirium in individuals 65 years of age and older who undergo orthopedic surgery after low energy lower extremity fractures (LELEF).
Biomarkers may play important roles in the detection, prediction and management of delirium especially in frail elderly individuals. Predictive biomarkers may help characterize an individual's susceptibility to delirium and thereby help specialized treatment, care and management of such individuals during their hospitalization. They may also help predict treatment response to a specific modality and help in selection of such modality. Recent studies performed in the UK and published in 2011 have measured plasma cholinesterase activity and determined that these levels were lower in patients who developed delirium compared with remaining subjects. Other studies have indicated that CRP may also have a role in delirium prediction as they have found that CRP measured on admission to an ICU had predictable changes that occurred within 24 hours that in turn were predictors of delirium. One the aims of the study is to compare the predictive and treatment response values of groups of biomarkers that have been hypothesized to be of predictive value.
Read the detailed description
Surgery causes oxidative stress on the brain9 leading to inflammation. Post-operative delirium has been linked with inflammation in the brain. Delirium has been hypothesized to be a central nervous system response to systemic inflammation during a state of blood-brain barrier (BBB) compromise.
Studies have shown a rise of inflammatory cytokines and fall of anti-inflammatory cytokines. Vice-versa, external cytokine administration has been shown to lead to delirium. Melatonin is known for its strong anti-oxidant and anti-inflammatory properties, this should account for its preventive properties in post-operative delirium. It has also been hypothesized that post-operative delirium in elderly is caused by circadian rhythm disturbances secondary to a relative lack of melatonin.
Keeping in mind the above two possible pathophysiology for delirium, investigators are expecting melatonin supplementation should be able to reduce the incidence of post-operative delirium particularly in elderly population.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
10 mg liquid Melatonin IR-SL at 7 pm for 1 week
PlaceboDrug
10 mg liquid placebo at 7 pm for 1 week
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Individuals who are randomized to the control arm will receive liquid placebo sublingually 60-90 minutes prior to surgery. Receives: Drug: Placebo |
| Melatonin | Active comparator | Individuals who are randomized to the treatment arm will receive 10 mg liquid IR-SL melatonin 60-90 minutes prior to surgery Receives: Drug: Melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Delirium assessment
The Delirium Rating Scale Revised (DRS-R98) will be given to all patients every day for seven days. Investigators will compare the scores recorded on day 7 between those receiving melatonin versus those receiving placebo controlling for their baseline performance.
Measured: 1 Week
Secondary outcomes (1)
Hospital stay
Length of hospital stay will be recorded for all patients and compared between the two treatment groups (i.e., those receiving melatonin and those receiving placebo).
Measured: 1 Week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study startJun 2015
- Primary completionJun 2018 (estimated)
- Study completionJun 2018 (estimated)
Why it stopped: Investigator found that a new study drug that is FDA approved would be superior to melatonin
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Muralidhara Rao, Loyola University
- Investigators
- Muralidhara S Rao, MD, Principal investigator, Loyola University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02903901
- Sponsor's protocol ID
- 206981
- Status last verified
- Sep 2016
- First submitted
- 13 Sep 2016
- Last updated
- 16 Sep 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009 Dec;103 Suppl 1(Suppl 1):i41-46. doi: 10.1093/bja/aep291.
PubMed 20007989Bekker AY, Weeks EJ. Cognitive function after anaesthesia in the elderly. Best Pract Res Clin Anaesthesiol. 2003 Jun;17(2):259-72. doi: 10.1016/s1521-6896(03)00005-3.
PubMed 12817919
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin for Prevention of Post- Operative Delirium Pilot Study Protocol
- ClinicalTrials.gov ID
- NCT02903901
- Acronym / sponsor ID
- 206981
- Conditions
- Delirium
- Keywords
- Delirium
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator found that a new study drug that is FDA approved would be superior to melatonin
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Jun 2018 (estimated)
- Study completion
- Jun 2018 (estimated)
- First posted
- 16 Sep 2016 (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.
To test the efficacy of melatonin compared to placebo in preventing post-operative delirium and reduction in intensity or duration of delirium in individuals 65 years of age and older who undergo orthopedic surgery after low energy lower extremity fractures (LELEF).
Biomarkers may play important roles in the detection, prediction and management of delirium especially in frail elderly individuals. Predictive biomarkers may help characterize an individual's susceptibility to delirium and thereby help specialized treatment, care and management of such individuals during their hospitalization. They may also help predict treatment response to a specific modality and help in selection of such modality. Recent studies performed in the UK and published in 2011 have measured plasma cholinesterase activity and determined that these levels were lower in patients who developed delirium compared with remaining subjects. Other studies have indicated that CRP may also have a role in delirium prediction as they have found that CRP measured on admission to an ICU had predictable changes that occurred within 24 hours that in turn were predictors of delirium. One the aims of the study is to compare the predictive and treatment response values of groups of biomarkers that have been hypothesized to be of predictive value.
Detailed description
Surgery causes oxidative stress on the brain9 leading to inflammation. Post-operative delirium has been linked with inflammation in the brain. Delirium has been hypothesized to be a central nervous system response to systemic inflammation during a state of blood-brain barrier (BBB) compromise.
Studies have shown a rise of inflammatory cytokines and fall of anti-inflammatory cytokines. Vice-versa, external cytokine administration has been shown to lead to delirium. Melatonin is known for its strong anti-oxidant and anti-inflammatory properties, this should account for its preventive properties in post-operative delirium. It has also been hypothesized that post-operative delirium in elderly is caused by circadian rhythm disturbances secondary to a relative lack of melatonin.
Keeping in mind the above two possible pathophysiology for delirium, investigators are expecting melatonin supplementation should be able to reduce the incidence of post-operative delirium particularly in elderly population.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIndividuals who are randomized to the control arm will receive liquid placebo sublingually 60-90 minutes prior to surgery. |
| Melatonin | Active comparator | Drug: MelatoninIndividuals who are randomized to the treatment arm will receive 10 mg liquid IR-SL melatonin 60-90 minutes prior to surgery |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (15 listed)
- Patients 65 years of age and older undergoing Low Energy Lower Extremity Fractures (LELEF) surgery
- Presence of an LELEF fracture
- Low Energy (e.g., falls from standing height, falls from sitting, etc.).
- Operative Fractures:
Key exclusion criteria (5 listed)
- Patients with previous adverse reaction or side-effects to melatonin
- Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
- Inability to communicate in English
- Patients with a Montreal Cognitive Assessment (MoCA) score of below 7 will not be included in the study because of their inability to give informed consent at that stage. This score is approximately 2 standard deviation below average score for Alzheimer's Dementia.
- Participants who are unable to give consent or communicate well in English will not be enrolled
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 |
|---|---|---|
| Melatonin10 mg liquid Melatonin IR-SL at 7 pm for 1 week | Drug | Melatonin |
| Placebo10 mg liquid placebo at 7 pm for 1 week | Drug | Placebo |
Primary outcome
Delirium assessment
Time frame: 1 Week
The Delirium Rating Scale Revised (DRS-R98) will be given to all patients every day for seven days. Investigators will compare the scores recorded on day 7 between those receiving melatonin versus those receiving placebo controlling for their baseline performance.
1 secondary outcome
Hospital stay
Time frame: 1 Week
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2016.
- Background: PubMed 20007989Deiner S, Silverstein JH. Postoperative delirium and cognitive dysfunction. Br J Anaesth. 2009 Dec;103 Suppl 1(Suppl 1):i41-46. doi: 10.1093/bja/aep291.
- Background: PubMed 12817919Bekker AY, Weeks EJ. Cognitive function after anaesthesia in the elderly. Best Pract Res Clin Anaesthesiol. 2003 Jun;17(2):259-72. doi: 10.1016/s1521-6896(03)00005-3.
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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.
Muralidhara S Rao, MD principal investigator
Loyola University
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 Melatonin in people with Delirium, run by Loyola University at 1 site in United States.
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 15 inclusion and 5 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: withdrawn, as of the sponsor's last update on 16 Sep 2016. 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 United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
Delirium assessment (time frame: 1 Week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02903901, which also lists 2 linked publications.
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 16 Sep 2016.