AnxietyPhase 4NCT01486615
Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone
A Phase 4 study testing meloset (melatonin), stresnil ( melatonin and alprazolam) and (alprax) alprazolam in people with Anxiety, run by B.P. Koirala Institute of Health Sciences at 2 sites in Nepal.
Trial summary
Background: Benzodiazepine, a common premedicant, suppresses endogenous melatonin levels and thus paradoxically increases episodes of arousal during sleep and thus causes restlessness and hangs over effects. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Anxiety
- What is being tested?
- meloset (melatonin), stresnil ( melatonin and alprazolam) and (alprax) alprazolam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesNepal
- Study dates
- Oct 2011to Jan 2012
- Phase
- Phase 4
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- (ASA 1\&2),
- aging 18 to 65 years
- having anxiety VAS score of more than 2
- posted for general anaesthesia with estimated duration of < 3 hours.
Who cannot join
- patients taking analgesics, sedatives, antiepileptics or antidepressants,
- suffering from obesity (BMI ≥ 28) or neuropsychiatric disease,
- having allergy to the study drugs
Trial locations and contacts
2 sites in 1 country.
Nepal2 sites
B. P. Koirala Institute of Health Sciences
Dharān, Koshi, 56700
Dr Krishna Pokharel
Dharān, Koshi, 56700
About this study
Official title: Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone: a Randomized, Double Blind Placebo Controlled Study
Background: Benzodiazepine, a common premedicant, suppresses endogenous melatonin levels and thus paradoxically increases episodes of arousal during sleep and thus causes restlessness and hangs over effects. Adding melatonin to it may decrease nocturnal arousal and promote the perception of sound sleep in the perioperative period.
Methods: Eighty patients (ASA 1\&2) with anxiety VAS ≥ 2 posted for general anaesthesia will be randomly assigned to receive 0.5 mg alprazolam (Group A), 3 mg melatonin, a combination of 0.5 mg alprazolam and 3 mg melatonin (Group AM), or a similar looking placebo (Group P), approximately 90 minutes before surgery.
Read the detailed description
Review of literature:
Benzodiazepines are among the most popular drugs used for preoperative medication to produce anxiolysis, amnesia, and sedation. However, they negatively influence sleep quality by decreasing the duration of REM sleep and slow wave sleep.
Alprazolam is more anxioselective than the more commonly used ones like midazolam, lorazepam and diazepam.Melatonin (N-acetyl-5-methoxytryptamine) is an emerging premedicant as it possesses anxiolytic and sedative properties without impairing cognitive or psychomotor skills.5 Moreover, it has an excellent safety profile.
We designed this prospective randomized double blind placebo controlled study to assess whether addition of melatonin to alprazolam has any benefit over alprazolam, melatonin or placebo alone as a premedication agent.
Rationale of the study Melatonin facilitates sleep onset and improves the quality of sleep. On the other hand, benzodiazepines suppress endogenous melatonin levels and thus paradoxically increase episodes of arousal during sleep causing restlessness and hang over effects (fatigue).
Hence, the rationale of using melatonin alprazolam combination is melatonin may decrease nocturnal arousal and promote the perception of sound sleep and thus reverse this unwanted side effect of alprazolam. Melatonin does not produce amnesia and adding a benzodiazepine to it may be desirable to achieve this desirable premedication effect.
Research design and methodology:
After getting approval from the institutional research ethics committee and written informed consent, we will study eighty patients. With the help of computer generated random numbers, patients will be assigned to one of the four groups (n=20) to receive vitamin B (Group P), 0.5 mg alprazolam (Group A), 3mg melatonin (Group M) or a combination of 0.5 mg alprazolam and 3 mg melatonin (Group AM) approximately 90 minutes before surgery. In addition to the study drugs, Groups A and AM will also receive vitamin B.
On the preanaesthetic visit one day prior to surgery, the patients will be explained about the nature of the study and the various scales to be used. A 10 cm linear Visual Analogue Scale (VAS) as well as Nepali version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) will be used to assess their anxiety level. The extremes of the VAS anxiety scale will be marked as 'no anxiety' at the 0 end and 'anxiety as bad as ever can be' at the 10 cm end. Sedation will be assessed with a 5 point scale (0=alert, 1=arouses to voice, 2=arouses with gentle tactile stimulation, 3=arouses with vigorous tactile stimulation, 4=lack of responsiveness) and orientation, with a 3 point scale (0=none, 1=orientation in either time or place, 2=orientation in both). To test for the memory, recall of 5 different simple pictures and 2 events will be assessed. Pictures to be used will be sequentially numbered on the back and their names printed on the front.
Approximately 2 hours prior to surgery, each patient will be taken to a quiet room. Non invasive blood pressure, heart rate, respiratory rate and SpO2 will be monitored. Then picture 1 (cup on a plate) and 2 (fruits) will be shown at 10 min before and just prior to the drug administration respectively. Patients will be asked to take the study medication orally with 15 ml of plain water according to the group assignment by an investigator not involved in the patient management and data collection thereafter. Then anxiety, sedation and orientation will be assessed at 15 min, 30 min and 1 hour after the drug administration. At these time points pictures 3 (bird), 4 (hare) and 5 (car) will also be shown respectively.
In the operating room, intravenous access will be secured and pethidine 1 mg/kg administered. Then intravenous lidocaine 20 mg bolus will be administered followed by propofol with infusion pump at 100 ml per hour till responses to verbal command and eyelash reflex are lost. Vecuronium 0.1 mg/kg and isoflurane in oxygen will be administered to maintain the adequate depth of anaesthesia. After intubation, ventilation will be adjusted to maintain normocapnia. Incremental doses of pethidine and vecuronium will be administered as needed on the discretion of the investigator blinded to the patient's group assignment. No other analgesics will be administered. After completion of surgery, intravenous neostigmine 50 microgram/kg and glycopyrrolate 10 microgram/kg will be given to reverse muscle paralysis. Anaesthesia time (induction to emergence) will be noted.
In the recovery room, patients will receive the standard postoperative care; including oxygen administration via face mask 6 L/min and monitoring of heart rate, respiratory rate, non invasive blood pressure and SpO2. Modified Aldrete score and sedation score will be assessed at 10 min and 30 min after extubation. Also the occurrence of nausea, vomiting, dizziness, headache and restlessness will be recorded till 24 hours. Vomiting will be managed with ondansetron 4 mg intravenously.
The next day, the patients will be asked if they recalled the two events; being transported to operating room and intravenous cannula being inserted. They will also be asked to have a free recall of the five pictures they were shown and the score will represent the numbers of pictures they recalled. Then the first five pictures that they were shown will be mixed with next 5 new pictures (of a horse, shoe, bicycle, elephant and tiger) and they will be asked to recognize those they had already seen. The score will represent the number of pictures correctly identified. They will also be asked whether they felt that premedication drug is required to relieve anxiety and also whether they would like to receive the same premedication drug in the future.
Statistical analysis: Data will be tested for normal distribution using Kolmogorov-Smirnov test. To identify differences between groups, one-way ANOVA will be used for normally distributed continuing data and chi square tests for categorical data. If the data is found to be not normally distributed; they will be analyzed with nonparametric statistical methods. Friedman repeated measures analysis of variance followed by Wilcoxon tests with Bonferroni correction will be used for within-group comparison of values between different time points. Kruskal Wallis tests with post hoc multiple comparisons by Mann Whitney U test will be used for the comparison of values between the groups at each time points. Parametric data will be expressed as the mean±SD and nonparametric data as median (interquartile range). A p value <0.05 will be considered significant.
- Conditions
- Anxiety
- Being tested
- meloset (melatonin), stresnil ( melatonin and alprazolam), (alprax) alprazolam, placebo
- Keywords
- premedication, premedicants, preoperative anxiety, melatonin, alprazolam
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
meloset (melatonin)Drug
3 mg melatonin tablet 1-2 hour prior surgery
stresnil ( melatonin and alprazolam)Drug
3 mg melatonin and 0.5 mg alprazolam 1-2 hr before anesthesia
(alprax) alprazolamDrug
0.5 mg alprazolam
placeboDrug
similar looking placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Placebo comparator | Premedication with 3 mg melatonin (Meloset) tablet orally 1-2 hour prior to anesthesia Receives: Drug: meloset (melatonin) |
| melatonin and alprazolam premedication | Placebo comparator | Premedication with 3 mg melatonin and 0.5 mg alprazolam (Stresnil) tablet orally 1-2 hrs prior to anesthesia Receives: Drug: stresnil ( melatonin and alprazolam) |
| alprazolam premedication | Placebo comparator | Premedication with 0.5 mg alprazolam (Alprax) tablet orally 1-2 hr prior to anesthesia Receives: Drug: (alprax) alprazolam |
| placebo premedication | Active comparator | Premedication with a similar looking placebo tablet orally 1-2 hr prior to anesthesia Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in VAS Anxiety Score Relative to Baseline After Premedication
VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.
Measured: Change from baseline in VAS anxiety score at 15 minutes after premedication
Change in VAS Anxiety Score Relative to Baseline at 30 Minutes After Premedication
VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.
Measured: Changes from baseline in VAS anxiety score at 30 minutes after premedication
Change in VAS Anxiety Score Relative to Baseline at One Hour After Premedication
VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.
Measured: Changes from baseline in VAS anxiety score at one hour after premedication
Secondary outcomes (5)
Sedation Score at One Hour After Premedication
Sedation level was assessed with a 5 point scale (0=alert, 1=arouses to voice, 2=arouses with gentle tactile stimulation, 3=arouses with vigorous tactile stimulation, 4=lack of responsiveness). Minimum score is 0 and Maximum is 4. The lesser the score, the better the outcome.
Measured: Sedation score at 1 hour after the premedication
Orientation Score
Orientation was assessed with a 3 point scale (0=none, 1=orientation in either time or place, 2=orientation in both). Minimum score is 0 and maximum is 2. The lesser the score, the lesser the effect on patients cognition and the better the outcome.
Measured: Orientation score at one hour after premedication
Number of Patients With Intact Memory
Number of patients who recalled or recognized the picture number five shown one hour after premedication. The more the number of patients with intact memory, the better the outcome.
Measured: 24 hour after surgery
Amount of Propofol Consumption
Dose of propofol needed for loss of response to verbal command was noted at the time of induction of general anesthesia. The lesser the propofol needed for the loss of response to verbal command, the better the outcome.
Measured: 1 - 2 hour after premedication
Number of Patients With Loss of Memory for Being Transferred to Operating Room.
Patients were asked whether they recalled the event of being transferred to the operating room before anaesthesia. The lesser the number of patients with amnesia, the better the outcome.
Measured: 24 hour after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2011 (estimated)
- Study startOct 2011
- Primary completionJan 2012
- Study completionJan 2012
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 (8)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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- B.P. Koirala Institute of Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Krishna Pokharel, B.P. Koirala Institute of Health Sciences
- Investigators
- Krishna Pokharel, MD, Principal investigator, B.P. Koirala Institute of Health SciencesBalkrishna Bhattarai, MD, Study director, B.P. Koirala Institute of Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01486615
- Sponsor's protocol ID
- 2/18 (Acd. 796/067/068)
- Status last verified
- Sep 2012
- First submitted
- 10 Nov 2011
- Last updated
- 5 Oct 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Naguib M, Samarkandi AH, Moniem MA, Mansour Eel-D, Alshaer AA, Al-Ayyaf HA, Fadin A, Alharby SW. The effects of melatonin premedication on propofol and thiopental induction dose-response curves: a prospective, randomized, double-blind study. Anesth Analg. 2006 Dec;103(6):1448-52. doi: 10.1213/01.ane.0000244534.24216.3a.
PubMed 17122221Naguib M, Samarkandi AH. The comparative dose-response effects of melatonin and midazolam for premedication of adult patients: a double-blinded, placebo-controlled study. Anesth Analg. 2000 Aug;91(2):473-9. doi: 10.1097/00000539-200008000-00046.
PubMed 10910871Naguib M, Samarkandi AH. Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. Br J Anaesth. 1999 Jun;82(6):875-80. doi: 10.1093/bja/82.6.875.
PubMed 10562782De Witte JL, Alegret C, Sessler DI, Cammu G. Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam. Anesth Analg. 2002 Dec;95(6):1601-6, table of contents. doi: 10.1097/00000539-200212000-00024.
PubMed 12456424Seabra ML, Bignotto M, Pinto LR Jr, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res. 2000 Nov;29(4):193-200. doi: 10.1034/j.1600-0633.2002.290401.x.
PubMed 11068941Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007 Oct;23(10):2597-605. doi: 10.1185/030079907X233098.
PubMed 17875243Wurtman RJ, Zhdanova I. Improvement of sleep quality by melatonin. Lancet. 1995 Dec 2;346(8988):1491. doi: 10.1016/s0140-6736(95)92509-0. No abstract available.
PubMed 7491013Pokharel K, Tripathi M, Gupta PK, Bhattarai B, Khatiwada S, Subedi A. Premedication with oral alprazolam and melatonin combination: a comparison with either alone--a randomized controlled factorial trial. Biomed Res Int. 2014;2014:356964. doi: 10.1155/2014/356964. Epub 2014 Jan 12.
PubMed 24527443
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Premedication With Melatonin and Alprazolam Combination Versus Alprazolam or Melatonin Alone: a Randomized, Double Blind Placebo Controlled Study
- ClinicalTrials.gov ID
- NCT01486615
- Acronym / sponsor ID
- 2/18 (Acd. 796/067/068)
- Conditions
- Anxiety
- Keywords
- premedication, premedicants, preoperative anxiety, melatonin, alprazolam
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- B.P. Koirala Institute of Health SciencesUniversity, hospital or other
- Study start
- Oct 2011
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 6 Dec 2011 (estimated)
- Results
- Posted 5 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background: Benzodiazepine, a common premedicant, suppresses endogenous melatonin levels and thus paradoxically increases episodes of arousal during sleep and thus causes restlessness and hangs over effects. Adding melatonin to it may decrease nocturnal arousal and promote the perception of sound sleep in the perioperative period.
Methods: Eighty patients (ASA 1\&2) with anxiety VAS ≥ 2 posted for general anaesthesia will be randomly assigned to receive 0.5 mg alprazolam (Group A), 3 mg melatonin, a combination of 0.5 mg alprazolam and 3 mg melatonin (Group AM), or a similar looking placebo (Group P), approximately 90 minutes before surgery.
Detailed description
Review of literature:
Benzodiazepines are among the most popular drugs used for preoperative medication to produce anxiolysis, amnesia, and sedation. However, they negatively influence sleep quality by decreasing the duration of REM sleep and slow wave sleep.
Alprazolam is more anxioselective than the more commonly used ones like midazolam, lorazepam and diazepam.Melatonin (N-acetyl-5-methoxytryptamine) is an emerging premedicant as it possesses anxiolytic and sedative properties without impairing cognitive or psychomotor skills.5 Moreover, it has an excellent safety profile.
We designed this prospective randomized double blind placebo controlled study to assess whether addition of melatonin to alprazolam has any benefit over alprazolam, melatonin or placebo alone as a premedication agent.
Rationale of the study Melatonin facilitates sleep onset and improves the quality of sleep. On the other hand, benzodiazepines suppress endogenous melatonin levels and thus paradoxically increase episodes of arousal during sleep causing restlessness and hang over effects (fatigue).
Hence, the rationale of using melatonin alprazolam combination is melatonin may decrease nocturnal arousal and promote the perception of sound sleep and thus reverse this unwanted side effect of alprazolam. Melatonin does not produce amnesia and adding a benzodiazepine to it may be desirable to achieve this desirable premedication effect.
Research design and methodology:
After getting approval from the institutional research ethics committee and written informed consent, we will study eighty patients. With the help of computer generated random numbers, patients will be assigned to one of the four groups (n=20) to receive vitamin B (Group P), 0.5 mg alprazolam (Group A), 3mg melatonin (Group M) or a combination of 0.5 mg alprazolam and 3 mg melatonin (Group AM) approximately 90 minutes before surgery. In addition to the study drugs, Groups A and AM will also receive vitamin B.
On the preanaesthetic visit one day prior to surgery, the patients will be explained about the nature of the study and the various scales to be used. A 10 cm linear Visual Analogue Scale (VAS) as well as Nepali version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS) will be used to assess their anxiety level. The extremes of the VAS anxiety scale will be marked as 'no anxiety' at the 0 end and 'anxiety as bad as ever can be' at the 10 cm end. Sedation will be assessed with a 5 point scale (0=alert, 1=arouses to voice, 2=arouses with gentle tactile stimulation, 3=arouses with vigorous tactile stimulation, 4=lack of responsiveness) and orientation, with a 3 point scale (0=none, 1=orientation in either time or place, 2=orientation in both). To test for the memory, recall of 5 different simple pictures and 2 events will be assessed. Pictures to be used will be sequentially numbered on the back and their names printed on the front.
Approximately 2 hours prior to surgery, each patient will be taken to a quiet room. Non invasive blood pressure, heart rate, respiratory rate and SpO2 will be monitored. Then picture 1 (cup on a plate) and 2 (fruits) will be shown at 10 min before and just prior to the drug administration respectively. Patients will be asked to take the study medication orally with 15 ml of plain water according to the group assignment by an investigator not involved in the patient management and data collection thereafter. Then anxiety, sedation and orientation will be assessed at 15 min, 30 min and 1 hour after the drug administration. At these time points pictures 3 (bird), 4 (hare) and 5 (car) will also be shown respectively.
In the operating room, intravenous access will be secured and pethidine 1 mg/kg administered. Then intravenous lidocaine 20 mg bolus will be administered followed by propofol with infusion pump at 100 ml per hour till responses to verbal command and eyelash reflex are lost. Vecuronium 0.1 mg/kg and isoflurane in oxygen will be administered to maintain the adequate depth of anaesthesia. After intubation, ventilation will be adjusted to maintain normocapnia. Incremental doses of pethidine and vecuronium will be administered as needed on the discretion of the investigator blinded to the patient's group assignment. No other analgesics will be administered. After completion of surgery, intravenous neostigmine 50 microgram/kg and glycopyrrolate 10 microgram/kg will be given to reverse muscle paralysis. Anaesthesia time (induction to emergence) will be noted.
In the recovery room, patients will receive the standard postoperative care; including oxygen administration via face mask 6 L/min and monitoring of heart rate, respiratory rate, non invasive blood pressure and SpO2. Modified Aldrete score and sedation score will be assessed at 10 min and 30 min after extubation. Also the occurrence of nausea, vomiting, dizziness, headache and restlessness will be recorded till 24 hours. Vomiting will be managed with ondansetron 4 mg intravenously.
The next day, the patients will be asked if they recalled the two events; being transported to operating room and intravenous cannula being inserted. They will also be asked to have a free recall of the five pictures they were shown and the score will represent the numbers of pictures they recalled. Then the first five pictures that they were shown will be mixed with next 5 new pictures (of a horse, shoe, bicycle, elephant and tiger) and they will be asked to recognize those they had already seen. The score will represent the number of pictures correctly identified. They will also be asked whether they felt that premedication drug is required to relieve anxiety and also whether they would like to receive the same premedication drug in the future.
Statistical analysis: Data will be tested for normal distribution using Kolmogorov-Smirnov test. To identify differences between groups, one-way ANOVA will be used for normally distributed continuing data and chi square tests for categorical data. If the data is found to be not normally distributed; they will be analyzed with nonparametric statistical methods. Friedman repeated measures analysis of variance followed by Wilcoxon tests with Bonferroni correction will be used for within-group comparison of values between different time points. Kruskal Wallis tests with post hoc multiple comparisons by Mann Whitney U test will be used for the comparison of values between the groups at each time points. Parametric data will be expressed as the mean±SD and nonparametric data as median (interquartile range). A p value <0.05 will be considered significant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Placebo comparator | Drug: meloset (melatonin)Premedication with 3 mg melatonin (Meloset) tablet orally 1-2 hour prior to anesthesia |
| melatonin and alprazolam premedication | Placebo comparator | Drug: stresnil ( melatonin and alprazolam)Premedication with 3 mg melatonin and 0.5 mg alprazolam (Stresnil) tablet orally 1-2 hrs prior to anesthesia |
| alprazolam premedication | Placebo comparator | Drug: (alprax) alprazolamPremedication with 0.5 mg alprazolam (Alprax) tablet orally 1-2 hr prior to anesthesia |
| placebo premedication | Active comparator | Drug: placeboPremedication with a similar looking placebo tablet orally 1-2 hr prior to anesthesia |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- (ASA 1\&2),
- aging 18 to 65 years
- having anxiety VAS score of more than 2
- posted for general anaesthesia with estimated duration of < 3 hours.
Key exclusion criteria (3 listed)
- patients taking analgesics, sedatives, antiepileptics or antidepressants,
- suffering from obesity (BMI ≥ 28) or neuropsychiatric disease,
- having allergy to the study drugs
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 |
|---|---|---|
| meloset (melatonin)3 mg melatonin tablet 1-2 hour prior surgery | Drug | Melatonin |
| stresnil ( melatonin and alprazolam)3 mg melatonin and 0.5 mg alprazolam 1-2 hr before anesthesia | Drug | melatonin and alprazolam premedication |
| (alprax) alprazolam0.5 mg alprazolam | Drug | alprazolam premedication |
| placebosimilar looking placebo tablet | Drug | placebo premedication |
Primary outcome
Change in VAS Anxiety Score Relative to Baseline After Premedication
Time frame: Change from baseline in VAS anxiety score at 15 minutes after premedication
VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.
Change in VAS Anxiety Score Relative to Baseline at 30 Minutes After Premedication
Time frame: Changes from baseline in VAS anxiety score at 30 minutes after premedication
VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.
Change in VAS Anxiety Score Relative to Baseline at One Hour After Premedication
Time frame: Changes from baseline in VAS anxiety score at one hour after premedication
VAS (Visual Analogue Score) Anxiety Scale is a 10 cm long scale with two sides, the patient side (front) and the clinicians side (back). The extremes of the front are colored as white and black with a gradual darkening of color from white to black. The back is marked in centimeter from 0 to 10 and 0 correlates with white color (no anxiety at all) and 10 correlates to black color (anxiety as bad as ever can be) on the front. As anxiety is worsened, the color is darker and score is more. The maximum score is 10 and minimum 0. The patient is asked to point on the scale according to his anxiety level. The anxiety score is the correlating number on the clinicians side. The more the reduction in anxiety from baseline, the better the outcome.
5 secondary outcomes
Sedation Score at One Hour After Premedication
Time frame: Sedation score at 1 hour after the premedication
Orientation Score
Time frame: Orientation score at one hour after premedication
Number of Patients With Intact Memory
Time frame: 24 hour after surgery
Amount of Propofol Consumption
Time frame: 1 - 2 hour after premedication
Number of Patients With Loss of Memory for Being Transferred to Operating Room.
Time frame: 24 hour after surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17122221Naguib M, Samarkandi AH, Moniem MA, Mansour Eel-D, Alshaer AA, Al-Ayyaf HA, Fadin A, Alharby SW. The effects of melatonin premedication on propofol and thiopental induction dose-response curves: a prospective, randomized, double-blind study. Anesth Analg. 2006 Dec;103(6):1448-52. doi: 10.1213/01.ane.0000244534.24216.3a.
- Background: PubMed 10910871Naguib M, Samarkandi AH. The comparative dose-response effects of melatonin and midazolam for premedication of adult patients: a double-blinded, placebo-controlled study. Anesth Analg. 2000 Aug;91(2):473-9. doi: 10.1097/00000539-200008000-00046.
- Background: PubMed 10562782Naguib M, Samarkandi AH. Premedication with melatonin: a double-blind, placebo-controlled comparison with midazolam. Br J Anaesth. 1999 Jun;82(6):875-80. doi: 10.1093/bja/82.6.875.
- Background: PubMed 12456424De Witte JL, Alegret C, Sessler DI, Cammu G. Preoperative alprazolam reduces anxiety in ambulatory surgery patients: a comparison with oral midazolam. Anesth Analg. 2002 Dec;95(6):1601-6, table of contents. doi: 10.1097/00000539-200212000-00024.
- Background: PubMed 11068941Seabra ML, Bignotto M, Pinto LR Jr, Tufik S. Randomized, double-blind clinical trial, controlled with placebo, of the toxicology of chronic melatonin treatment. J Pineal Res. 2000 Nov;29(4):193-200. doi: 10.1034/j.1600-0633.2002.290401.x.
- Background: PubMed 17875243Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007 Oct;23(10):2597-605. doi: 10.1185/030079907X233098.
- Background: PubMed 7491013Wurtman RJ, Zhdanova I. Improvement of sleep quality by melatonin. Lancet. 1995 Dec 2;346(8988):1491. doi: 10.1016/s0140-6736(95)92509-0. No abstract available.
- Derived from this study: PubMed 24527443Pokharel K, Tripathi M, Gupta PK, Bhattarai B, Khatiwada S, Subedi A. Premedication with oral alprazolam and melatonin combination: a comparison with either alone--a randomized controlled factorial trial. Biomed Res Int. 2014;2014:356964. doi: 10.1155/2014/356964. Epub 2014 Jan 12.
Related trials for Anxiety
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Recruiting
Effect of a Brief Daily Digital Meditation on Well-Being in US Young Adults (BEGIN II)
Mental Health and General Well-being
Not yet recruitingObservational study
Functional Impact of Psychological Symptoms in Patients With Superior Semicircular Canal Dehiscence Syndrome (SSCD): a National Cross-sectional Study
Superior Semicircular Canal Dehiscence
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.
Krishna Pokharel, MD principal investigator
B.P. Koirala Institute of Health Sciences
Balkrishna Bhattarai, MD study director
B.P. Koirala Institute of Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing meloset (melatonin), stresnil ( melatonin and alprazolam) and (alprax) alprazolam in people with Anxiety, run by B.P. Koirala Institute of Health Sciences at 2 sites in Nepal.
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 4 inclusion and 3 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 5 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Nepal. 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?
Yes. Results are posted in the registry (first posted 5 Oct 2012). 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?
Change in VAS Anxiety Score Relative to Baseline After Premedication (time frame: Change from baseline in VAS anxiety score at 15 minutes after premedication). The study lists 3 primary outcomes in all. 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 NCT01486615, which also lists 8 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 5 Oct 2012.