<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03790462</url>
  </required_header>
  <id_info>
    <org_study_id>2017-0174</org_study_id>
    <nct_id>NCT03790462</nct_id>
  </id_info>
  <brief_title>Select Indian Ragas on Electrophysiological Parameters</brief_title>
  <acronym>RAGA-2</acronym>
  <official_title>Evaluation of the Effect of Select Indian Ragas on Electrophysiological Parameters and Salivary Stress Markers - a Randomized Control Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MS Ramaiah Medical College &amp; Hospitals</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Indian Council of Medical Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>MS Ramaiah Medical College &amp; Hospitals</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In India, music is predominantly used as entertainment. Despite ample vedic literature&#xD;
      available on the beneficial effects of ragas in Indian music on human mind and body,&#xD;
      scientific evidence for the same is extremely meager. This initial systematic study of 6&#xD;
      ragas, is an attempt to provide scientific evidence and validate the use of Indian classical&#xD;
      music &amp; thus present the scientific community with a new complementary therapy / non-&#xD;
      pharmacological mode of treatment which could be used in prevention of various&#xD;
      non-communicable diseases. In our previous study on prehypertensives and hypertensives, blood&#xD;
      pressure (BP) reduced significantly after listening to Indian music [raga 'bhimpalas' (raga&#xD;
      that normalizes BP)], daily for 3 months. Heart rate variability (HRV) recorded once on&#xD;
      recruitment and end of study failed to show any change. On retrospection, we realised that&#xD;
      the effect of only a single raga had been tested and the acute effects had not been&#xD;
      elucidated. Specifically, EEG waves &amp; cognitive ERPs were not studied. Hence a study&#xD;
      encompassing all the 6 ragas that are known to normalize BP as given in literatures such as&#xD;
      Gandharva Veda (Sama Veda) &amp; Raga Chikitsa was planned. Among these, 3 ragas are now being&#xD;
      studied &amp; data analysis is in line. This proposal is to study the immediate&#xD;
      electrophysiological changes with remaining 3 ragas. Music can be prescribed as a cheap and&#xD;
      effective adjuvant in the treatment of hypertension along with other lifestyle modifications.&#xD;
      To the best of our knowledge, there is scanty literature testing Indian ragas. Thus there is&#xD;
      a great need to address this issue.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INDIAN MUSIC: 'Raga' (musical scale) is a set of musical notes presented in an orderly manner&#xD;
      in order to generate a melody out of the same. Matanga (9-10th century AD) in his work&#xD;
      'Brihaddeshi' was the earliest to define raga as &quot;raga is that kind of sound composition&#xD;
      consisting of melodic movements which has the effect of colouring the hearts of men&quot;.&#xD;
      However, there have been very few studies which have used Indian classical music as an&#xD;
      intervention for studying their health benefits. Gandharvaveda, a part of Sama veda, has&#xD;
      mentioned various ragas to have myriad health benefits.Dr. Burnell has mentioned a manuscript&#xD;
      named raga chikistsa in the collections of Saraswati Mahal Library in Tanjore which deals&#xD;
      with the various ragas that can be used for curing various ailments. For example raga&#xD;
      Malkauns is said to help in curing hypotension. Insomnic patients are said to benefit by&#xD;
      usage of raga Behag. 'Heart Rate Variability' has become the conventionally accepted term to&#xD;
      describe beat-to-beat alteration in HR, and RR intervals in ECG. The cause of HRV is&#xD;
      considered to be respiratory sinus arrhythmia as well as low-frequency oscillations (0.1 Hz)&#xD;
      associated with Traube-Hering-Mayer waves of BP . It was found that a decrease in HRV was a&#xD;
      strong predictor of mortality after acute myocardial infarction . HRV is assessed by either&#xD;
      time or frequency domain methods. EFFECT OF MUSIC ON BLOOD PRESSURE:Many studies have shown&#xD;
      that there is a modification of cardiorespiratory parameters on repeated rhythymic recitation&#xD;
      of a prayer, poetry or yoga mantra . So it is not surprising that music (rhythmic repetition&#xD;
      of notes and tones) can also have similar effects. A number of studies have reported that&#xD;
      listening to sedative music (slow tempo, legato phrasing, and minimal dynamic contrasts) can&#xD;
      lead to decreased HR and BP. BP was shown to be proportional to the crescendo present in&#xD;
      music, where as music with uniform emphasis reduced the BP .&#xD;
&#xD;
      Passive listening to music on a daily basis helped in reducing BP of 12 elderly subjects. The&#xD;
      experimental group listened to selected songs for 25 minutes every day, for four weeks. BP&#xD;
      was measured twice a week. There was a significant decrease in the mean BP: 11.8 mmHg in the&#xD;
      SBP and 4.7 mmHg in the DBP . Elderly subjects have shown statistically significant reduction&#xD;
      in SBP and DBP after 12-minute audio relaxation program . STUDIES ON EFFECT OF MUSIC ON HRV:&#xD;
      Whether music causes an increase or decrease in HR, remains a mystery . Several studies&#xD;
      reported that under various conditions music decreases sympathetic nervous system (SNS) and&#xD;
      increases parasympathetic nervous system (PNS) activity as measured by HR and HRV, indicating&#xD;
      physiological relaxation . No difference in HR or HRV was observed by a few investigators .&#xD;
      However, an increase in HR has also been reported by some . SALIVARY STRESS MARKERS: The&#xD;
      salivary glands receive sympathetic and parasympathetic innervations. The major enzyme that&#xD;
      is released on sympathetic stimulation is alpha (α) amylase. Thus it is presumed that,&#xD;
      changes in salivary alpha amylase indicate the activity of the SM system during stress.&#xD;
      Further, both salivary cortisol and alpha amylase have been used by number of researchers&#xD;
      recently to quantify stress or as biomarkers of stress. Nevertheless, it has also been put&#xD;
      forth that salivary amylase activity is an index of plasma norepinephrine levels under a&#xD;
      variety of stressful conditions. STUDIES ON EFFECT OF MUSIC ON EEG: In one study where EEG&#xD;
      was recorded after giving alpha music to about ten subjects, it was observed that increase in&#xD;
      the maximum amplitudes of Alpha waves either after 6 minutes or after 12 minutes of alpha&#xD;
      music. However, the maximum amplitude of beta waves showed a decline of up to 40% from the&#xD;
      initial value. These results, namely, the increase in Alpha activity and decrease in Beta&#xD;
      activity indicate that subjects experience 'relaxed alertness'.&#xD;
&#xD;
      Setting: Medical college and Tertiary care hospital Case group (totally 3 groups) = 35&#xD;
      subjects in each group; a total sample of 105 Control group = 35 subjects Basis for sample&#xD;
      size:Based on the study conducted by Okada et al, it was found that RMSSD (root mean square&#xD;
      standard deviation of NN intervals on ECG) was 17.4±7.2 ms and 24.1±15.5 ms before and after&#xD;
      music therapy with an effect size of 0.59 and power of 90% and confidence interval of 95%,&#xD;
      the minimum sample size required for the present study was estimated to be 32.&#xD;
&#xD;
      Methods and materials: The effect of at least 3 different Indian classical music ragas on the&#xD;
      autonomic functions and brain waves of subjects will be studied. Healthy subjects will be&#xD;
      recruited from M S Ramaiah Instituitions. Selection bias will be avoided by randomization&#xD;
      using computer generated random numbers. All numbers generated will be kept in an opaque and&#xD;
      sealed envelope. The envelope will be opened by the research assistant after the baseline&#xD;
      assessment of each participant and assigned to each of the seven groups randomly, into all&#xD;
      intervention and control categories. Each group will randomly be assigned to listen to a&#xD;
      particular raga using block randomization. The control group, the seventh group, will not&#xD;
      receive any raga, but HRV,BP, EEG and saliva will be recorded and collected. Literature given&#xD;
      in Gandharva veda and raga chikitsa will be used to choose ragas which have varied health&#xD;
      benefits especially on the cardiovascular system. The ragas which have been said to normalize&#xD;
      the BP are ahir bhairav, bhimpalas, hindol, puriya, kausikanada and todi. Ahir Bhairav, Kausi&#xD;
      Kanada &amp; Bhimpalas will be used for the present study. Detailed methodology: The&#xD;
      investigators will include a few questions inquiring the subjects' preference of type of&#xD;
      music, previous experience with music instrumental or vocal training and note the same. A&#xD;
      general health check up will be done for all subjects. The BMI, waist hip ratio and BP in&#xD;
      sitting position measured twice after five minutes rest (Sphygmomanometry) in between will be&#xD;
      noted. A stress questionnaire (State Trait Anxiety Inventory) will be administered prior to&#xD;
      and after intervention to assess the baseline level of stress and the change in stress levels&#xD;
      after music intervention.&#xD;
&#xD;
      Subjects will be made to lie supine and relax for ten minutes. EEG electrodes will be applied&#xD;
      according to 10-20 system. A baseline EEG (Galileo NT) and ECG in lead II for 10 minutes&#xD;
      (Power lab 15 T Labchart by AD instruments) will be recorded. Baseline digital measurement of&#xD;
      BP will be done. Saliva for baseline stress markers (cortisol and amylase) will be collected.&#xD;
      All the subjects will be instructed to breathe at a rate of 6 breaths per minute, throughout&#xD;
      the procedure that will be monitored by the software. After this, a raga from Indian&#xD;
      classical music will be played for 10 minutes duration via earplugs connected to the laptop,&#xD;
      during which time the recording of ECG and EEG will continue. The time of start of music will&#xD;
      be marked using an event marker in the software. Post ten minutes, the music will be stopped&#xD;
      and BP will be recorded and saliva will be collected. ECG and EEG recording will continue for&#xD;
      another ten minutes to study any residual effects of music on the heart after which BP will&#xD;
      be recorded and saliva will be collected again (end of 30 minutes procedure). Stress&#xD;
      questionnaire will be administered at the end of the procedure. For those in control group&#xD;
      baseline BP, ECG and EEG will be recorded for ten minutes under resting conditions. Saliva&#xD;
      will be collected and stored. EEG will be analyzed using Galileo NT software. HRV will be&#xD;
      analyzed using the software provided. The saliva samples will be centrifuged at 3000 rpm for&#xD;
      15 minutes and supernatant saliva stored at -20° C until further analysis for cortisol and&#xD;
      amylase (ELISA).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">February 9, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>It is a triple blinded study</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Blood pressure</measure>
    <time_frame>Baseline, 10 minutes after music intervention &amp; 10 minutes post intervention</time_frame>
    <description>in mm Hg</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Electroencephalogram amplitude</measure>
    <time_frame>Baseline, 10 minutes during music intervention &amp; 10 minutes post intervention</time_frame>
    <description>Change in Electroencephalogram (EEG) waves amplitude (in mV)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Electroencephalogram Frequency</measure>
    <time_frame>Baseline, 10 minutes during music intervention &amp; 10 minutes post intervention</time_frame>
    <description>Change in Electroencephalogram Frequency (in Hz)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Stress using state trait anxiety inventory</measure>
    <time_frame>Baseline, after 10 minutes of music intervention &amp; 10 minutes post intervention</time_frame>
    <description>State trait anxiety inventory score in numbers - It comprises separate self-report scales for measuring two distinct anxiety concepts: state anxiety and trait anxiety. The STAI-T scale consists of 20 statements that ask people to describe how they generally feel. The STAI-S scale also consists of 20 statements. Each question is rated on a 4-point scale (not at all, somewhat, moderately so, very much so). The range of possible scores for form Y of the STAI varies from a minimum score of 20 to a maximum score of 80 on both the STAI-T and STAI-S subscales. STAI scores are commonly classified as &quot;no or low anxiety&quot; (20-37), &quot;moderate anxiety&quot; (38-44), and &quot;high anxiety&quot; (45-80).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Heart rate variability</measure>
    <time_frame>Baseline, 10 minutes during music intervention &amp; 10 minutes post intervention</time_frame>
    <description>Analyzed in lead II of Electrocardiogram - time and frequency domain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Salivary Cortisol</measure>
    <time_frame>Baseline, after 10 minutes of music intervention &amp; 10 minutes post intervention</time_frame>
    <description>Change in level of salivary cortisol will be analyzed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Salivary alpha amylase</measure>
    <time_frame>Baseline, after 10 minutes of music intervention &amp; 10 minutes post intervention</time_frame>
    <description>Change in level of salivary alpha amylase will be analyzed</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">166</enrollment>
  <condition>Psychology, Social</condition>
  <condition>Stress</condition>
  <condition>Stress, Psychological</condition>
  <arm_group>
    <arm_group_label>Music intervention group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Raga &quot;A&quot; will be played for 10 minutes &amp; data collected.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Music intervention group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Raga &quot;B&quot; will be played for 10 minutes &amp; data collected.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Music intervention group 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Raga &quot;C&quot; will be played for 10 minutes &amp; data collected.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Subject relaxes without music for 10 minutes and electrophysiological parameters will be collected</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Music intervention</intervention_name>
    <description>A raga out of 3 select Indian classical ragas &quot;Puriya/Hindol/Todi&quot; will be played for 10 minutes &amp; data collected.</description>
    <arm_group_label>Music intervention group 1</arm_group_label>
    <arm_group_label>Music intervention group 2</arm_group_label>
    <arm_group_label>Music intervention group 3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects&#xD;
&#xD;
          -  Age group of 18-30 years&#xD;
&#xD;
          -  Either gender will be included as autonomic functions change with age&#xD;
&#xD;
          -  Non smokers&#xD;
&#xD;
          -  Non alcoholics.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any cardiovascular disorders,&#xD;
&#xD;
          -  Renal disorders,&#xD;
&#xD;
          -  Respiratory disorders,&#xD;
&#xD;
          -  Endocrine disorders,&#xD;
&#xD;
          -  Neurological problems&#xD;
&#xD;
          -  Pregnancy,&#xD;
&#xD;
          -  Body mass index (BMI)&gt;30 kg/m2,&#xD;
&#xD;
          -  Hearing problems,&#xD;
&#xD;
          -  Psychiatric disorder&#xD;
&#xD;
          -  Drugs which are known to affect the BP or autonomic status of the individual&#xD;
&#xD;
          -  Other impairments that prevent the subject from performing few experimental procedures&#xD;
             will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MEDHA RAO Y, MD</last_name>
    <role>Study Chair</role>
    <affiliation>M S Ramaiah Medical college and hospitals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>M S Ramaiah Medical college and hospitals</name>
      <address>
        <city>Bangalore</city>
        <state>Karnataka</state>
        <zip>560054</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 31, 2018</study_first_posted>
  <last_update_submitted>February 10, 2021</last_update_submitted>
  <last_update_submitted_qc>February 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>MS Ramaiah Medical College &amp; Hospitals</investigator_affiliation>
    <investigator_full_name>KIRTHANA KUNIKULLAYA U</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Stress, Electroencephalogram,Indian Music, Electrocardiogram</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stress, Psychological</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Publications (Pre-press) may be shared with other researchers</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03790462
org study id: 2017-0174
nct id: NCT03790462
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In India, music is predominantly used as entertainment. Despite ample vedic literature
      available on the beneficial effects of ragas in Indian music on human mind and body,
      scientific evidence for the same is extremely meager. This initial systematic study of 6
      ragas, is an attempt to provide scientific evidence and validate the use of Indian classical
      music & thus present the scientific community with a new complementary therapy / non-
      pharmacological mode of treatment which could be used in prevention of various
      non-communicable diseases. In our previous study on prehypertensives and hypertensives, blood
      pressure (BP) reduced significantly after listening to Indian music [raga 'bhimpalas' (raga
      that normalizes BP)], daily for 3 months. Heart rate variability (HRV) recorded once on
      recruitment and end of study failed to show any change. On retrospection, we realised that
      the effect of only a single raga had been tested and the acute effects had not been
      elucidated. Specifically, EEG waves & cognitive ERPs were not studied. Hence a study
      encompassing all the 6 ragas that are known to normalize BP as given in literatures such as
      Gandharva Veda (Sama Veda) & Raga Chikitsa was planned. Among these, 3 ragas are now being
      studied & data analysis is in line. This proposal is to study the immediate
      electrophysiological changes with remaining 3 ragas. Music can be prescribed as a cheap and
      effective adjuvant in the treatment of hypertension along with other lifestyle modifications.
      To the best of our knowledge, there is scanty literature testing Indian ragas. Thus there is
      a great need to address this issue.
INDIAN MUSIC: 'Raga' (musical scale) is a set of musical notes presented in an orderly manner
      in order to generate a melody out of the same. Matanga (9-10th century AD) in his work
      'Brihaddeshi' was the earliest to define raga as "raga is that kind of sound composition
      consisting of melodic movements which has the effect of colouring the hearts of men".
      However, there have been very few studies which have used Indian classical music as an
      intervention for studying their health benefits. Gandharvaveda, a part of Sama veda, has
      mentioned various ragas to have myriad health benefits.Dr. Burnell has mentioned a manuscript
      named raga chikistsa in the collections of Saraswati Mahal Library in Tanjore which deals
      with the various ragas that can be used for curing various ailments. For example raga
      Malkauns is said to help in curing hypotension. Insomnic patients are said to benefit by
      usage of raga Behag. 'Heart Rate Variability' has become the conventionally accepted term to
      describe beat-to-beat alteration in HR, and RR intervals in ECG. The cause of HRV is
      considered to be respiratory sinus arrhythmia as well as low-frequency oscillations (0.1 Hz)
      associated with Traube-Hering-Mayer waves of BP . It was found that a decrease in HRV was a
      strong predictor of mortality after acute myocardial infarction . HRV is assessed by either
      time or frequency domain methods. EFFECT OF MUSIC ON BLOOD PRESSURE:Many studies have shown
      that there is a modification of cardiorespiratory parameters on repeated rhythymic recitation
      of a prayer, poetry or yoga mantra . So it is not surprising that music (rhythmic repetition
      of notes and tones) can also have similar effects. A number of studies have reported that
      listening to sedative music (slow tempo, legato phrasing, and minimal dynamic contrasts) can
      lead to decreased HR and BP. BP was shown to be proportional to the crescendo present in
      music, where as music with uniform emphasis reduced the BP .

      Passive listening to music on a daily basis helped in reducing BP of 12 elderly subjects. The
      experimental group listened to selected songs for 25 minutes every day, for four weeks. BP
      was measured twice a week. There was a significant decrease in the mean BP: 11.8 mmHg in the
      SBP and 4.7 mmHg in the DBP . Elderly subjects have shown statistically significant reduction
      in SBP and DBP after 12-minute audio relaxation program . STUDIES ON EFFECT OF MUSIC ON HRV:
      Whether music causes an increase or decrease in HR, remains a mystery . Several studies
      reported that under various conditions music decreases sympathetic nervous system (SNS) and
      increases parasympathetic nervous system (PNS) activity as measured by HR and HRV, indicating
      physiological relaxation . No difference in HR or HRV was observed by a few investigators .
      However, an increase in HR has also been reported by some . SALIVARY STRESS MARKERS: The
      salivary glands receive sympathetic and parasympathetic innervations. The major enzyme that
      is released on sympathetic stimulation is alpha (α) amylase. Thus it is presumed that,
      changes in salivary alpha amylase indicate the activity of the SM system during stress.
      Further, both salivary cortisol and alpha amylase have been used by number of researchers
      recently to quantify stress or as biomarkers of stress. Nevertheless, it has also been put
      forth that salivary amylase activity is an index of plasma norepinephrine levels under a
      variety of stressful conditions. STUDIES ON EFFECT OF MUSIC ON EEG: In one study where EEG
      was recorded after giving alpha music to about ten subjects, it was observed that increase in
      the maximum amplitudes of Alpha waves either after 6 minutes or after 12 minutes of alpha
      music. However, the maximum amplitude of beta waves showed a decline of up to 40% from the
      initial value. These results, namely, the increase in Alpha activity and decrease in Beta
      activity indicate that subjects experience 'relaxed alertness'.

      Setting: Medical college and Tertiary care hospital Case group (totally 3 groups) = 35
      subjects in each group; a total sample of 105 Control group = 35 subjects Basis for sample
      size:Based on the study conducted by Okada et al, it was found that RMSSD (root mean square
      standard deviation of NN intervals on ECG) was 17.4±7.2 ms and 24.1±15.5 ms before and after
      music therapy with an effect size of 0.59 and power of 90% and confidence interval of 95%,
      the minimum sample size required for the present study was estimated to be 32.

      Methods and materials: The effect of at least 3 different Indian classical music ragas on the
      autonomic functions and brain waves of subjects will be studied. Healthy subjects will be
      recruited from M S Ramaiah Instituitions. Selection bias will be avoided by randomization
      using computer generated random numbers. All numbers generated will be kept in an opaque and
      sealed envelope. The envelope will be opened by the research assistant after the baseline
      assessment of each participant and assigned to each of the seven groups randomly, into all
      intervention and control categories. Each group will randomly be assigned to listen to a
      particular raga using block randomization. The control group, the seventh group, will not
      receive any raga, but HRV,BP, EEG and saliva will be recorded and collected. Literature given
      in Gandharva veda and raga chikitsa will be used to choose ragas which have varied health
      benefits especially on the cardiovascular system. The ragas which have been said to normalize
      the BP are ahir bhairav, bhimpalas, hindol, puriya, kausikanada and todi. Ahir Bhairav, Kausi
      Kanada & Bhimpalas will be used for the present study. Detailed methodology: The
      investigators will include a few questions inquiring the subjects' preference of type of
      music, previous experience with music instrumental or vocal training and note the same. A
      general health check up will be done for all subjects. The BMI, waist hip ratio and BP in
      sitting position measured twice after five minutes rest (Sphygmomanometry) in between will be
      noted. A stress questionnaire (State Trait Anxiety Inventory) will be administered prior to
      and after intervention to assess the baseline level of stress and the change in stress levels
      after music intervention.

      Subjects will be made to lie supine and relax for ten minutes. EEG electrodes will be applied
      according to 10-20 system. A baseline EEG (Galileo NT) and ECG in lead II for 10 minutes
      (Power lab 15 T Labchart by AD instruments) will be recorded. Baseline digital measurement of
      BP will be done. Saliva for baseline stress markers (cortisol and amylase) will be collected.
      All the subjects will be instructed to breathe at a rate of 6 breaths per minute, throughout
      the procedure that will be monitored by the software. After this, a raga from Indian
      classical music will be played for 10 minutes duration via earplugs connected to the laptop,
      during which time the recording of ECG and EEG will continue. The time of start of music will
      be marked using an event marker in the software. Post ten minutes, the music will be stopped
      and BP will be recorded and saliva will be collected. ECG and EEG recording will continue for
      another ten minutes to study any residual effects of music on the heart after which BP will
      be recorded and saliva will be collected again (end of 30 minutes procedure). Stress
      questionnaire will be administered at the end of the procedure. For those in control group
      baseline BP, ECG and EEG will be recorded for ten minutes under resting conditions. Saliva
      will be collected and stored. EEG will be analyzed using Galileo NT software. HRV will be
      analyzed using the software provided. The saliva samples will be centrifuged at 3000 rpm for
      15 minutes and supernatant saliva stored at -20° C until further analysis for cortisol and
      amylase (ELISA).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: It is a triple blinded study
measure: Change in Blood pressure
time frame: Baseline, 10 minutes after music intervention & 10 minutes post intervention
description: in mm Hg
measure: Change in Electroencephalogram amplitude
time frame: Baseline, 10 minutes during music intervention & 10 minutes post intervention
description: Change in Electroencephalogram (EEG) waves amplitude (in mV)
measure: Change in Electroencephalogram Frequency
time frame: Baseline, 10 minutes during music intervention & 10 minutes post intervention
description: Change in Electroencephalogram Frequency (in Hz)
measure: Change in Stress using state trait anxiety inventory
time frame: Baseline, after 10 minutes of music intervention & 10 minutes post intervention
description: State trait anxiety inventory score in numbers - It comprises separate self-report scales for measuring two distinct anxiety concepts: state anxiety and trait anxiety. The STAI-T scale consists of 20 statements that ask people to describe how they generally feel. The STAI-S scale also consists of 20 statements. Each question is rated on a 4-point scale (not at all, somewhat, moderately so, very much so). The range of possible scores for form Y of the STAI varies from a minimum score of 20 to a maximum score of 80 on both the STAI-T and STAI-S subscales. STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80).
measure: Change in Heart rate variability
time frame: Baseline, 10 minutes during music intervention & 10 minutes post intervention
description: Analyzed in lead II of Electrocardiogram - time and frequency domain
measure: Change in Salivary Cortisol
time frame: Baseline, after 10 minutes of music intervention & 10 minutes post intervention
description: Change in level of salivary cortisol will be analyzed
measure: Change in Salivary alpha amylase
time frame: Baseline, after 10 minutes of music intervention & 10 minutes post intervention
description: Change in level of salivary alpha amylase will be analyzed
arm group label: Music intervention group 1
arm group type: Experimental
description: Raga "A" will be played for 10 minutes & data collected.
arm group label: Music intervention group 2
arm group type: Experimental
description: Raga "B" will be played for 10 minutes & data collected.
arm group label: Music intervention group 3
arm group type: Experimental
description: Raga "C" will be played for 10 minutes & data collected.
arm group label: Control group
arm group type: No Intervention
description: Subject relaxes without music for 10 minutes and electrophysiological parameters will be collected
intervention type: Other
intervention name: Music intervention
description: A raga out of 3 select Indian classical ragas "Puriya/Hindol/Todi" will be played for 10 minutes & data collected.
arm group label: Music intervention group 1
arm group label: Music intervention group 2
arm group label: Music intervention group 3
criteria: 
gender: All
minimum age: 18 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: MEDHA RAO Y, MD
role: Study Chair
affiliation: M S Ramaiah Medical college and hospitals
facility: 
country: India
responsible party type: Principal Investigator
investigator affiliation: MS Ramaiah Medical College & Hospitals
investigator full name: KIRTHANA KUNIKULLAYA U
investigator title: Principal Investigator
mesh term: Stress, Psychological
sharing ipd: No
ipd description: Publications (Pre-press) may be shared with other researchers