AnxietyPhase 3ANAN-MelatoninNCT02386319
Anxiolytic and Analgesic Effects of Melatonin
A Phase 3 study testing Melatonin in people with Anxiety, run by Herlev Hospital at 1 site in Denmark.
Trial summary
The study's main objective is to investigate melatonin's anxiolytic and sleep-regulating effects in patients undergoing surgery. Moreover, the investigators intend to investigate the pharmacokinetic parameters of melatonin in this patient population. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Anxiety
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2016to Apr 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients who are candidates for breast surgery.
- BMI between 18 and 30
- Visible veins in the elbow region
- Fertile women use anti-contraception and have performed a negative pregnancy test
- Male patients who are candidates for inguinal or umbilical hernia reapir
Who cannot join
- Patients, who use daily opioids, benzodiazepines or melatonin
- Patients diagnosed with a psychiatric disorder (defined as in medical treatment)
- Patients with severe physical disease (ASA 3-4)
- Patients with previous or ongoing alcohol or drug abuse
- Patients with liver disease (defined as in medical treatment)
- Patients diagnosed sleep disturbances
Show all 22Show fewer
- Patients who are unable to cooperate according to the protocol
- Patients with allergy to melatonin
- Patients, who use daily opioids, benzodiazepines or melatonin
- Patients diagnosed with a psychiatric disorder (defined as in medical treatment)
- Patients with severe physical disease (ASA 3-4)
- Patients with previous or ongoing alcohol or drug abuse
- Patients with liver disease (defined as in medical treatment)
- Patients diagnosed sleep disturbances
- Patients who are unable to cooperate according to the protocol
- Patients with allergy to melatonin
- Withdrawal- and drop-out criteria part 2:
- Patients can withdraw at any time during trial
- Complications during surgery occur that lead to:
- Immediate reoperation
- Hospitalization to intensive care unit
- If it is considered in the best interest of the patients physical- and psychological health to withdraw from the trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Anxiolytic and Analgesic Effects of Melatonin: A Randomized, Double-blinded, Placebo-controlled Clinical Study
The study's main objective is to investigate melatonin's anxiolytic and sleep-regulating effects in patients undergoing surgery. Moreover, the investigators intend to investigate the pharmacokinetic parameters of melatonin in this patient population.
Read the detailed description
The study is separated into two parts. In the first part the patients are undergoing cosmetic breast surgery, and in the second part the patient undergo inguinal og umbilical surgery.
The first part is a cohort at 12 patients undergoing breast surgery. All patients in this group will be treated with melatonin, and the investigators intend to investigate the pharmacokinetic parameters of melatonin. Melatonin will be administrated 60 min. before surgery and the evening after surgery at 9 pm.
All patients will receive an intravenous catheter. The intravenous catheter will be used for blood sampling. A baseline blood sample will be taken 65 min before surgery (baseline) and thereafter blood samples will be obtained 0 min., 15 min., 30 min., 45 min., 60 min., 90 min., 120 min., 180 min., 240 min., 300 min., 360 min. and 420 min. after administration of melatonin. Blood samples will be obtained again after administration of melatonin at 9 pm. in the evening in the same manner as described above. Plasma samples will be stored at minus 80 C and analyzed at the research laboratory of the Department of surgery, Herlev Hospital. The analysis will be preformed with the RIA-technique.
The second part is a randomized, double-blind, placebo-controlled study with a total of 32 participants divided into a intervention group (16) and a placebo group (16). In this part the investigators intend to investigate the anxiolytic and sleep-promoting effects of melatonin. Melatonin and placebo will be administrated at 9 pm. the evening before surgery, 120 min. before surgery, immediately after surgery in the PACU and at 9 pm the evening after surgery.
Anxiety will be measured by the State-Trait Anxiety Inventory (STAI) and a VAS-scale (0 mm = no anxiety and 100 mm = worst anxiety). Quality of sleep will be measured at the VAS-scale as well (0 mm = best sleep and 100 = worst sleep).
Randomization will be performed by a computer at randomization.com. The "first generator" function is used. The randomization will be preformed in blocks of 4 patients in each.
Manufacturing of medications and randomization will be made by an independent pharmacist.
The primary outcome is preoperative anxiety as measured on the STAI. A previous study investigated preoperative anxiety before hernia surgery and found a mean of 35.4 (SD 10.0) on the STAI scale. There does not exist any generally accepted measure of how large a change on the STAI scale constitutes a clinically important difference. However, a change equal to one standard deviation has been suggested. In the present study, this corresponds to a minimal relevant difference (MIREDIF) of 10 points on the STAI scale or 28%. A power of 80% was defined, a significance level of 5% and a minimal relevant difference (MIREDIF) of 28%. From these assumptions, 16 patients in each treatment group is needed
Statistics Anxiety and sleep quality will be compared at individual timepoints between groups Comparison will be performed either by Mann-whitheys-test or unpaired t-test, depending on the distribution of data. Values are considered significant at a p-value at 5% or less. Data will be reported as mean (SD) or median (IQR) depending on the distribution of data.
Data for the blood samples will be presented as AUC plasma concentrations, half-life, maximum concentration and time to maximum concentration.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Gelatin capsules
PlaceboDrug
Placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Active comparator | Melatonin 10 mg, gelatin capsules. Pharmacokinetic study: 10 mg x 2. In the morning before surgery and in the evening after surgery.
Anxiolytic and analgesic study: 10 mg x 4. Evening the day before surgery, the morning before surgery, immediately after surgery and the evening after surgery. Receives: Drug: Melatonin |
| Placebo | Placebo comparator | Gelatin capsules. Anxiolytic and analgesic study. Evening the day before surgery, the morning before surgery, immediately after surgery and the evening after surgery. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preoperative Anxiety
The "State" scale of the State-Trait Anxiety Inventory (STAI). Construct: Current level of anxiety. Scale range: 20-40 (higher scores indicate higher level of current anxiety) Scores are calculated according to the STAI scoring manual by adding point from each item (possible point for each item is 1-4).
Measured: 60 minutes preoperative
Secondary outcomes (9)
Postoperative Anxiety
State-Trait Anxiety Index
Measured: at the preoperative interview, 60 minutes prior to surgery and 4 hours postoperatively.
Pre- and Postoperative Anxiety
Visual analog scale
Measured: at the preoperative interview, 60 minutes prior to surgery, 1 and 4 hours postoperatively.
Intraoperative Requirement of Remifentanil
µg/kg/min
Measured: intraopeative
Intraoperative Requirement of Propofol
mg/kg/min
Measured: intraoperative
Use of Rescue-opioids in the PACU
dose
Measured: 0-24 hours postoperative
Use of Rescue-opioids in the Ward
dose
Measured: 0-24 hours postoperative
Perioperative Sleep Quality
Visual analog scale
Measured: 24 hours
General Well-being and Fatigue
Visual analog scale
Measured: 24 hours
Plasma Concentrations of Melatonin
pg/ml
Measured: baseline, 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, 360 min and 420 min. after melatonin administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2015 (estimated)
- Study startAug 2016
- Primary completionMar 2021
- Study completionApr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnxietyStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dennis Bregner Zetner, Herlev Hospital
- Investigators
- Dennis B Zetner, MD., Principal investigator, Herlev Hospital, Herlev Ringvej 75, Herlev, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02386319
- Sponsor's protocol ID
- Melatonin1234
- Acronym
- ANAN-Melatonin
- Status last verified
- Aug 2021
- First submitted
- 24 Feb 2015
- Last updated
- 2 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Madsen BK, Zetner D, Moller AM, Rosenberg J. Melatonin for preoperative and postoperative anxiety in adults. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD009861. doi: 10.1002/14651858.CD009861.pub3.
PubMed 33319916
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anxiolytic and Analgesic Effects of Melatonin: A Randomized, Double-blinded, Placebo-controlled Clinical Study
- ClinicalTrials.gov ID
- NCT02386319
- Acronym / sponsor ID
- ANAN-Melatonin / Melatonin1234
- Conditions
- Anxiety
- Keywords
- Melatonin, Surgery, Pharmacokinetic, Anxiolytic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Mar 2021 (actual)
- Study completion
- Apr 2021 (actual)
- First posted
- 11 Mar 2015 (estimated)
- Results
- Posted 2 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study's main objective is to investigate melatonin's anxiolytic and sleep-regulating effects in patients undergoing surgery. Moreover, the investigators intend to investigate the pharmacokinetic parameters of melatonin in this patient population.
Detailed description
The study is separated into two parts. In the first part the patients are undergoing cosmetic breast surgery, and in the second part the patient undergo inguinal og umbilical surgery.
The first part is a cohort at 12 patients undergoing breast surgery. All patients in this group will be treated with melatonin, and the investigators intend to investigate the pharmacokinetic parameters of melatonin. Melatonin will be administrated 60 min. before surgery and the evening after surgery at 9 pm.
All patients will receive an intravenous catheter. The intravenous catheter will be used for blood sampling. A baseline blood sample will be taken 65 min before surgery (baseline) and thereafter blood samples will be obtained 0 min., 15 min., 30 min., 45 min., 60 min., 90 min., 120 min., 180 min., 240 min., 300 min., 360 min. and 420 min. after administration of melatonin. Blood samples will be obtained again after administration of melatonin at 9 pm. in the evening in the same manner as described above. Plasma samples will be stored at minus 80 C and analyzed at the research laboratory of the Department of surgery, Herlev Hospital. The analysis will be preformed with the RIA-technique.
The second part is a randomized, double-blind, placebo-controlled study with a total of 32 participants divided into a intervention group (16) and a placebo group (16). In this part the investigators intend to investigate the anxiolytic and sleep-promoting effects of melatonin. Melatonin and placebo will be administrated at 9 pm. the evening before surgery, 120 min. before surgery, immediately after surgery in the PACU and at 9 pm the evening after surgery.
Anxiety will be measured by the State-Trait Anxiety Inventory (STAI) and a VAS-scale (0 mm = no anxiety and 100 mm = worst anxiety). Quality of sleep will be measured at the VAS-scale as well (0 mm = best sleep and 100 = worst sleep).
Randomization will be performed by a computer at randomization.com. The "first generator" function is used. The randomization will be preformed in blocks of 4 patients in each.
Manufacturing of medications and randomization will be made by an independent pharmacist.
The primary outcome is preoperative anxiety as measured on the STAI. A previous study investigated preoperative anxiety before hernia surgery and found a mean of 35.4 (SD 10.0) on the STAI scale. There does not exist any generally accepted measure of how large a change on the STAI scale constitutes a clinically important difference. However, a change equal to one standard deviation has been suggested. In the present study, this corresponds to a minimal relevant difference (MIREDIF) of 10 points on the STAI scale or 28%. A power of 80% was defined, a significance level of 5% and a minimal relevant difference (MIREDIF) of 28%. From these assumptions, 16 patients in each treatment group is needed
Statistics Anxiety and sleep quality will be compared at individual timepoints between groups Comparison will be performed either by Mann-whitheys-test or unpaired t-test, depending on the distribution of data. Values are considered significant at a p-value at 5% or less. Data will be reported as mean (SD) or median (IQR) depending on the distribution of data.
Data for the blood samples will be presented as AUC plasma concentrations, half-life, maximum concentration and time to maximum concentration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Active comparator | Drug: MelatoninMelatonin 10 mg, gelatin capsules. Pharmacokinetic study: 10 mg x 2. In the morning before surgery and in the evening after surgery. Anxiolytic and analgesic study: 10 mg x 4. Evening the day before surgery, the morning before surgery, immediately after surgery and the evening after surgery. |
| Placebo | Placebo comparator | Drug: PlaceboGelatin capsules. Anxiolytic and analgesic study. Evening the day before surgery, the morning before surgery, immediately after surgery and the evening after surgery. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Patients who are candidates for breast surgery.
- BMI between 18 and 30
- Visible veins in the elbow region
- Fertile women use anti-contraception and have performed a negative pregnancy test
- Male patients who are candidates for inguinal or umbilical hernia reapir
Key exclusion criteria (22 listed)
- Patients, who use daily opioids, benzodiazepines or melatonin
- Patients diagnosed with a psychiatric disorder (defined as in medical treatment)
- Patients with severe physical disease (ASA 3-4)
- Patients with previous or ongoing alcohol or drug abuse
- Patients with liver disease (defined as in medical treatment)
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 |
|---|---|---|
| MelatoninGelatin capsules | Drug | Melatonin |
| PlaceboPlacebo capsules | Drug | Placebo |
Primary outcome
Preoperative Anxiety
Time frame: 60 minutes preoperative
The "State" scale of the State-Trait Anxiety Inventory (STAI). Construct: Current level of anxiety. Scale range: 20-40 (higher scores indicate higher level of current anxiety) Scores are calculated according to the STAI scoring manual by adding point from each item (possible point for each item is 1-4).
9 secondary outcomes
Postoperative Anxiety
Time frame: at the preoperative interview, 60 minutes prior to surgery and 4 hours postoperatively.
Pre- and Postoperative Anxiety
Time frame: at the preoperative interview, 60 minutes prior to surgery, 1 and 4 hours postoperatively.
Intraoperative Requirement of Remifentanil
Time frame: intraopeative
Intraoperative Requirement of Propofol
Time frame: intraoperative
Use of Rescue-opioids in the PACU
Time frame: 0-24 hours postoperative
Use of Rescue-opioids in the Ward
Time frame: 0-24 hours postoperative
Perioperative Sleep Quality
Time frame: 24 hours
General Well-being and Fatigue
Time frame: 24 hours
Plasma Concentrations of Melatonin
Time frame: baseline, 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, 360 min and 420 min. after melatonin administration.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33319916Madsen BK, Zetner D, Moller AM, Rosenberg J. Melatonin for preoperative and postoperative anxiety in adults. Cochrane Database Syst Rev. 2020 Dec 8;12(12):CD009861. doi: 10.1002/14651858.CD009861.pub3.
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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.
Dennis B Zetner, MD. principal investigator
Herlev Hospital, Herlev Ringvej 75, Herlev, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Melatonin in people with Anxiety, run by Herlev Hospital at 1 site in Denmark.
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 5 inclusion and 22 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 2 Sep 2021. 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 Denmark. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Preoperative Anxiety (time frame: 60 minutes preoperative). 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 NCT02386319, which also lists 1 linked publication.
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 2 Sep 2021.