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CTRI Number  CTRI/2018/02/012032 [Registered on: 21/02/2018] Trial Registered Prospectively
Last Modified On: 20/06/2018
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug
Surgical/Anesthesia 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   comparing oral melatonin with oral clonidine as a drug given before anaesthesia, on anaesthetic usage and post operative pain in patients undergoing general anaesthesia 
Scientific Title of Study   Comparison of oral melatonin and clonidine as premedication on isoflurane consumption and postoperative analgesia in patients undergoing general anaesthesia– A randomised controlled trial 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ranjitha Gangadharaiah 
Designation  Assistant professor 
Affiliation  bangalore medical college and research institute 
Address  bangalore medical college and research institute , department of anaesthesiology, centenery building 3rd floor, fort road, kr road

Bangalore
KARNATAKA
560002
India 
Phone  9880243626  
Fax    
Email  ranjithagangadharaiah@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Ranjitha Gangadharaiah 
Designation  Assistant professor 
Affiliation  bangalore medical college and research institute 
Address  bangalore medical college and research institute , department of anaesthesiology, centenery building 3rd floor, fort road, kr road

Bangalore
KARNATAKA
560002
India 
Phone  9880243626  
Fax    
Email  ranjithagangadharaiah@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Ranjitha Gangadharaiah 
Designation  Assistant professor 
Affiliation  bangalore medical college and research institute 
Address  bangalore medical college and research institute , department of anaesthesiology, centenery building 3rd floor, fort road, kr road

Bangalore
KARNATAKA
560002
India 
Phone  9880243626  
Fax    
Email  ranjithagangadharaiah@gmail.com  
 
Source of Monetary or Material Support  
Dr Ranjitha Gangadharaiah, Bangalore medical college, department of anaesthesiology , centenery building, 3rd floor, fort road, kr road , bangalore 560002 
 
Primary Sponsor  
Name  Dr Ranjitha Gangadharaiah 
Address  Bangalore medical college and research institute , department of anaesthesiology, centenery building , 3rd floor, fort road, kr road, bangalore 560002 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ranjitha Gangadharaiah  Bangalore medical College and research institute  Department of anaesthesiology, centenery building,3rd floor,fort road, KR Road, Bangalore 560002
Bangalore
KARNATAKA 
9880243626

ranjithagangadharaiah@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Bangalore medical college and research institute ethical committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  ASA 1 patients undergoing general anaesthesia,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  melatonin and clonidine  tab melatonin 3mg and tab clonidine 100microgram 
Comparator Agent  melatonin, clonidine, control  tab melatonin 3mg, clonidine 100microgram and placebo control group 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Both 
Details  1) Patients who give written informed consent (Annexure I)
2) Patients belonging to ASA Grade I and II (Annexure II)
3) Age between 18-60 yrs
4) BMI between 18.9- 24.9 kg/m2
 
 
ExclusionCriteria 
Details  1) Patient refusal
2) Patients with systemic disorders
3) Patients with psychiatric illness

 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Participant and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
To compare the effects of oral melatonin and clonidine as premedication on
1) isoflurane consumption
2) postoperative analgesia
 
Isoflurane consumption: every 30minutes till the end of surgery
Post operative analgesia: till the visual analogue scale is more than 5
 
 
Secondary Outcome  
Outcome  TimePoints 
to study the safety profile of melatonin and clonidine 
 
Target Sample Size   Total Sample Size="75"
Sample Size from India="75" 
Final Enrollment numbers achieved (Total)= "75"
Final Enrollment numbers achieved (India)="75" 
Phase of Trial   Phase 4 
Date of First Enrollment (India)   01/03/2018 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) 08/06/2018 
Estimated Duration of Trial   Years="0"
Months="3"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   none yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

     Although there are significant improvements in peri-operative pain management, fear and anxiety are still the major hurdles that prevent several patients from undergoing surgical interventions. There are many drugs used orally to reduce anxiety preoperatively like midazolam, clonidine, melatonin, gabapentin, etc .  Midazolam is known to cause postoperative cognitive and pschycomotor impairment (1). Gabapentin causes nausea, vomiting and higher levels of sedation(2). Hence a drug without these side effects is preferred.

    Melatonin is a hormone secreted by the pineal gland(3). Melatonin exerts an effect on sleep by amplifying day/night differences in alertness and sleep quality. Melatonin has several functions that make it an attractive option for premedication including the regulation of circadian rhythm sedative, analgesic, anti inflammatory and antioxidant effects(4). Melatonin interacts with  multiple receptor sites including opioidergic, benzodiazepinergic, muscarinic, nicotinic, serotonergic, α1, α2 adrenergic and most importantly MT1/MT2 melatonergic receptors present in the dorsal horn of the spinal cord as well  in the central nervous system(5).

      Clonidine is an α-2 adrenoreceptor agonist which produces analgesia by its central action(6,7). It is rapidly absorbed after oral administration. It reaches a peak plasma concentration within 60-90mins. Clonidine stimulates alpha 2 adrenergic neurons in the medullary vasomotor centre causing a decrease in the sympathetic nervous system outflow from the Central nervous system to the peripheral tissues and central activation of non adrenergic imidazoline preferring receptors. Decreased sympathetic activity is manifested as peripheral vasodilatation, hypotension, decrease in heart rate and cardiac output.

      Some studies have proved that melatonin is an effective alternative to clonidine used in premedication especially in patients with low blood pressure. But they have used melatonin 5mg and clonidine 150µg (8). Some studies have shown that melatonin has similar efficacy compared to clonidine in reducing postoperative pain and narcotic consumption. Some studies have used 6mg of melatonin and 200 µg of clonidine (9) . There are some studies which have inferred that clonidine reduces the requirement of intraoperative isoflurane concentration (10) , but there are very few studies which have compared the anaesthetic consumption when melatonin or clonidine is given as premedication.

    Hence we have undertaken this study to compare the effects of oral melatonin 3mg and clonidine 100µg as premedication on isoflurane consumption and postoperative analgesia in patients undergoing GA.

 
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