NEED FOR THE STUDY:

Hypertension[HTN] is a leading preventable cause of premature death worldwide.1 It is mainly asymptomatic and remains undiagnosed until the disease progresses. It may lead to cardiovascular disease, renal failure, stroke and death if not intervened on time. Complications of hypertension account for 9.4 million deaths worldwide every year.2 Hypertension is directly responsible for 57% of all stroke deaths and 24% of all coronary heart disease deaths in India.3

Powerful antihypertensive drugs like Beta blockers, Calcium channel blockers and ACE inhibitors are now available to manage hypertension. In majority of cases, patient needs life-long treatment which leads to distressing side effects.4 Considering the above limitations, in recent years more attention has been paid to medications of herbal origin. However, till date the real potential of Ayurvedic medicine in the care of hypertension remains undocumented. The efficacy and safety of these medications remains to be evaluated. Although the availability of health-care services has risen, the quality of treatment received from different health-care providers is not consistent.5 Fewer than 1 in 5 people with hypertension have the problem under control6. Hence researchers are exploring for the possible beneficial effects from Alternative and complimentary systems of medicines.

Previous Ayurvedic studies proved effective in managing HTN through Panchakarma modalities and Shamana aushadhi7,8. The efficacy of Sarpagandha-ghana-vati in essential hypertension has been proven in some previous studies.9 However there is scarcity of studies with a randomised controlled design and with use of standard control like conventional Antihypertensives. Hence the current study was planned to validate the efficacy of Sarpagandhaghana vati in Hypertension.

REVIEW OF LITERATURE:

Hypertension also known as high blood pressure is a condition in which there is a persistently raised blood pressure. In Ayurveda, it is relatable to raktagata vata, raktavrita vata, siravata, kaphavrita vyana etc. HTN is diagnosed when systolic & diastolic readings on two different days is equal or above 140 mmHg & 90 mmHg respectievely.10

Though not common, symptoms like headache, nausea, confusion etc., are seen in some cases. If left untreated it leads to ischemic heart diseases and stroke causing death. Samprapti involves tridosha and rajo dushti of manas, but predominantly of vyana vata and rakta dhatu. Vyana vata mainly is considered responsible for maintenance of circulation. when vitiated vata reaches siras it causes pain, constriction and dilation sometimes even bulging. When this vyana vata gets avarana by kapha it alters the speed of circulation resulting in HTN. HTN is divided into primary [essential] and secondary HTN where 90-95% of adult cases are of primary. In some cases increased activity of sympathetic nervous system is found.11,12

TABLE OF DRUG REVIEW13

SARPAGANDHA GHANA VATI [ Siddhi yoga sangraha , yoga no.-111 ]

DRUG

LATIN NAME

PART USED

PROPORTION

KARMA

Sarpagandha

Rauwolfiaserpentina Benth ex. Kurz

Root

10 parts

Shoola prashmani,

Kaphavaathara,

Hrudaya avasadini

Jatamansi

Nardostachysjatamansi Dc

Root

1 part

Kaphashamakam,

Kaantibala prada,

Rakata doshakaret,

pittaghni,sheetlaa,

ParasikaYavani

HyoscyamusnigerLinn

Seeds

2 parts

Nidra janana,

Hrudayaavasadini,

Hrudayabala karaka,

Shotha hara

Pippalimula

Piper longum Linn.

Root

½ part

Hrudaya,mootral,

Rakta vardhak,

Rakta shodhak,

medhya,vaathara

Bhanga

Cannabis sativaLinn.

Leaves

1 part

Madakari,

Pralapajanana,

Nidrajanana,

Sulaprashamana

TABLE OF RASA PANCHAKA14

DRUG

RASA

GUNA

VEERYA

VIPAKA

DOSHAKARMA

Sarpagandha

Tikta

Rooksha

Ushna

Katu

Kaphavata hara

Jatamansi

Tikta, Kashaya, madhura

Teekshna, laghu, snigdha

Sheeta

Katu

Tridosha hara

Parasika yavani

Tikta, katu

Rooksha, guru, ushna

Ushna

Katu

Kaphavata hara

Pippalimoola

Katu

Teekshna, laghu, snigdha

Ushna

Madhura

Vata hara

Pithakara

Bhang

Tikta

Laghu, tikshna, ruksha

Ushna

Katu

Vatahara

PREVIOUS WORKS DONE

Dr. Dhanpat Mishra et al 2016 proved the efficacy of sarpagandha ghana vati on systolic, diastolic blood pressure, Hamilton anxiety rating scale over 35 patients when administered 1 gm /day for 30 days.15

Dr.jyothi Mishra et al 2011 proved the efficacy of sarpagandhaghan vati on systolic and diastolic blood pressure over 20 patients when administered 1 gm /day for 8 weeks.16

AIM AND OBJECTIVE:

AIM :

 To evaluate the efficacy of sarpagandha ghana vati in the management of Essential hypertension.

OBJECTIVES:

To compare the efficacy of sarpagandha ghana vati and amlodipine in the management of essential hypertension

To evaluate the efficacy of sarpagandha ghana vati on systolic, diastolic blood pressure , Sleep profile, Psychological states (anxiety, depression) and quality of life in essential hypertension

RESEARCH QUESTION

Does Sarpagandha ghana vati administered 500 mg BD for 60 days has efficacy in the management of essential hypertension?

HYPOTHESIS:

 H0- Effect of sarpagandha ghana vati and amlodipine in the management of essential hypertension are comparable

H1 – Effect of sarpagandha ghana vati and amlodipine in the management of essential hypertension are not comparable

MATERIALS

Literary source

The source of the data for the present study will be taken from classical texts, modern books, research articles, journals and internet.

Drug source

Sarpagandha ghana vati will be procured from GMP certified Ayurveda pharmacy

Subjects

 The patients with age between 20 to 70 years , fulfilling JNC criteria 8 for diagnosis of Essential hypertension will be taken for the study, from OPD and IPD section of K.L.E. Ayurveda Hospital & Medical research center, Shahapur- Belagavi.

METHODODLOGY

RESEARCH DRUG

Sarpagandha ghana vati

AUTHENTICATION:

Will be obtained from GMP certified pharmacy

DRUG PREPARATION METHOD

Drug will be procured from GMP certified pharmacy

PACKING AND STORAGE

Procured drug will be stored under standard storing conditions at MRC, KLE Ayurveda hospital.

STUDY TYPE

 Interventional

STUDY DESIGN

Randomised controlled clinical trial

MASKING

ï‚· Open label

CONTROL

ï‚· Control

END POINT

ï‚· Efficacy of sarpagandhaghana vati and comparability to amlodipine in the management of essential hypertension.

After approval of ethical clearance all subjects will be randomised into groups with method of randomisation and will begin the study.

GROUPS : 2

GROUP A :35

 GROUP B : 35

SAMPLE SIZE:

 70

GROUPS & INTERVENTION

GROUP

SAMPLE SIZE

INTERVENTION

DURATION

FOLLOWUP

Group A

[Trial]

35

Sarpagandha ghana vati 500mg BD A/F with water

60 days

Every 15 days

Group B

[Control]

35

Amlodipine 5mg OD with water.

60 days

Every 15 days

DIAGNOSTIC CRITERIA :

 Patients meeting the diagnostic criteria Stage 1 of hypertension recommended by JNC 8 will be recruited in the study 17

INCLUSION & EXCLUSION CRITERIA

Inclusion Criteria

 Criteria for the selection of the patients will be based on the criteria suggested by Joint National Committee 8. 18

In patients aged less than 60 years with Systolic Blood Pressure (SBP) greater than 140 mm Hg and Diastolic Blood Pressure (DBP) greater than 90 mm Hg

 In patients aged more than 60 years with Systolic Blood pressure greater than 150 mm Hg and Diastolic Blood Pressure greater than 90 mm Hg

Stages of Grade 1 Hypertension. (SBP-140-159, DBP-90-99mm Hg)

Patients between 20-70 years age of either sex.

Exclusion Criteria

Ischemic heart disease (IHD), Coronary heart disease (CHD), Coronary artery disease (CAD) and coarctation of aorta

 Renal failure

Endocrine diseases,

 Hypertension with cerebral complications e.g. hypertensive encephalopathy, cerebral haemorrhage, convulsive seizure.

Malignant hypertension

Pregnant and Lactating female patients

Patient on treatment for hypertension since 1 month.

WITHDRAWAL CRITERIA

1. Any serious adverse events requiring major interventions.

2. Any time during the study continuation of study drug could lead to harmful effect.

3. Any untoward event where in investigator feels continuation of trial may jeopardise the health state of the patient.

4. Subjects failure to follow the instructions of the Principal Investigator .

5. If patient needs treatment that are not allowed in the study.

6. Other administrative reasons.

RESCUE MEDICATION

Patients developing aggravation /worsening of present clinical condition would be referred to appropriate specialist /centre and will be administered rescue medications. Such patients will be excluded from the study

STUDY DRUG DOSE

500 mg BD

ROUTE OF ADMINISTRATION

Oral

STUDY SITE

ï‚· KLE Ayurveda hospital & Medical Research Center, shahapur, Belagavi.

STUDY PERIOD

18 months

ASSESSMENT CRITERIA

SUBJECTIVE PARAMETERS :

Primary Assessment Criteria -

Systolic blood pressure

Diastolic blood pressure

Secondary Assessment Criteria –

 Mean arterial pressure

Depression Anxiety Stress Scale long form (DASS-42) 19

Short Form 36 – Quality of life 20

2 weeks sleep diary 21

Pittsburgh Sleep Quality Index (PSQI)22

FREQUENCY OF ASSESSMENT

Assessment will be done on every 15th day.

[ 0th day - 15th day - 30th day - 45th day - 60th day]

STATISTICAL METHODS TO ANALYSE THE DATA

ï‚· Assessment of Quantitative parameters within group will be assessed by Paired t-test and between groups will be assessed with independent sample t-test. Assessment of qualitative parameters for between groups will be assessed with Mann Whitney test. Level of significance P<0.05

EXPECTED OUTCOME

Change may be helpful in the better management of essential hypertension

ETHICAL Clearance No. : BMK/20/PG/KC/3

CTRI Registration No. :

BIBLIOGRAPHIC REFERENCES.

1. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation. 2016 Aug 9;134(6):441-50. doi: 10.1161/CIRCULATIONAHA.115.018912. PMID: 27502908; PMCID: PMC4979614.

2. Graham LA, Dominiczak AF, Ferreri NR. Role of renal transporters and novel regulatory interactions in the TAL that control blood pressure. Physiol Genomics. 2017 May 1;49(5):261-276. doi: 10.1152/physiolgenomics.00017.2017. Epub 2017 Apr 7. PMID: 28389525; PMCID: PMC5451551.

3. Gupta R. Trends in hypertension epidemiology in India. J Hum Hypertens. 2004 Feb;18(2):73-8. doi: 10.1038/sj.jhh.1001633. PMID: 14730320. 4. Chen HY, Ma KY, Hsieh PL, Liou YS, Jong GP. Long-term Effects of Antihypertensive Drug Use and New-onset Osteoporotic Fracture in Elderly Patients: A Population-based Longitudinal Cohort Study. Chin Med J (Engl). 2016 Dec 20;129(24):2907-2912. doi: 10.4103/0366-6999.195472. PMID: 27958221; PMCID: PMC5198524. 5. Mehndiratta A, Sharma S, Gupta NP, Sankar MJ, Cluzeau F. Adapting clinical guidelines in India-a pragmatic approach. BMJ. 2017 Nov 17;359:j5147. doi: 10.1136/bmj.j5147. PMID: 29150419; PMCID: PMC5691554.

6. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation. 2016 Aug 9;134(6):441-50. doi: 10.1161/CIRCULATIONAHA.115.018912. PMID: 27502908; PMCID: PMC4979614. 7. Shukla G, Bhatted SK, Dave AR, Shukla VD. Efficacy of Virechana and Basti Karma with Shamana therapy in the management of essential hypertension: A comparative study. Ayu. 2013 Jan;34(1):70-6. doi: 10.4103/0974-8520.115455. PMID: 24049408; PMCID: PMC3764884 8. Ali A, Umar D, Farhan M, Basheer B, Baroudi K. Effect of Brahmyadi Churna (Brahmi, Shankhapushpi, Jatamansi, Jyotishmati, Vacha, Ashwagandha) and tablet Shilajatu in essential hypertension: An observational study. J Adv Pharm Technol Res. 2015 Oct-Dec;6(4):148-53. doi: 10.4103/2231-4040.165015. PMID: 26605154; PMCID: PMC4630720.

9. Mishra D, Tubaki BR. Effect of Brahmi vati and Sarpagandha Ghana vati in management of essential hypertension - A randomized, double blind, clinical study. J Ayurveda Integr Med. 2019 Oct-Dec;10(4):269-276. doi: 10.1016/j.jaim.2017.04.001. Epub 2017 Dec 11. PMID: 29242090; PMCID: PMC6938844.

10. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation. 2016 Aug 9;134(6):441-50. doi: 10.1161/CIRCULATIONAHA.115.018912. PMID: 27502908; PMCID: PMC4979614. Kaushik RM, Mahajan SK, Rajesh V,

11. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation. 2016 Aug 9;134(6):441-50. doi: 10.1161/CIRCULATIONAHA.115.018912. PMID: 27502908; PMCID: PMC4979614. Kaushik RM, Mahajan SK, Rajesh V,

12. Kaushik R. Stress profile in essential hypertension. Hypertens Res. 2004 Sep;27(9):619-24. doi: 10.1291/hypres.27.619. PMID: 15750254

13. Ayurveda sarasangraha, vati prakarana, Published by Shri Baidyanath Ayurveda Bhavana Limited ,Nani, Allahabada. 2010, pp 467

14. PandeyGynendra, DravyagunaVijnana, Part-1, Chowkhambakrishnadas Academy, Varanasi,3rd Edn. 2005 pg no 15. Mishra D, Tubaki BR. Effect of Brahmi vati and Sarpagandha Ghana vati in management of essential hypertension - A randomized, double blind, clinical study. J Ayurveda Integr Med. 2019 Oct-Dec;10(4):269-276. doi: 10.1016/j.jaim.2017.04.001. Epub 2017 Dec 11. PMID: 29242090; PMCID: PMC6938844. 16. Mishra J, Joshi NP, Pandya DM. A comparative study of Shankhapushpyadi Ghana Vati and Sarpagandhadi Ghana Vati in the management of "Essential Hypertension". Ayu. 2012 Jan;33(1):54-61. doi: 10.4103/0974-8520.100311. PMID: 23049185; PMCID: PMC3456865. 17. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb

5;311(5):507-20. doi: 10.1001/jama.2013.284427. Erratum in: JAMA. 2014 May 7;311(17):1809. PMID: 24352797. 18. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et.al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20. doi: 10.1001/jama.2013.284427. Erratum in: JAMA. 2014 May 7;311(17):1809. PMID: 24352797 19. Osman A, Wong JL, Bagge CL, Freedenthal S, Gutierrez PM, Lozano G. The Depression Anxiety Stress Scales-21 (DASS-21): further examination of dimensions, scale reliability, and correlates. J Clin Psychol. 2012 Dec;68(12):1322-38. doi: 10.1002/jclp.21908. Epub 2012 Aug 28. PMID: 22930477. 20. Newnham EA, Harwood KE, Page AC. Evaluating the clinical significance of responses by psychiatric inpatients to the mental health subscales of the SF-36. J Affect Disord. 2007 Feb;98(1-2):91-7. doi: 10.1016/j.jad.2006.07.001. Epub 2006 Aug 10. PMID: 16904752. 21. Kawada T. Agreement rates for sleep/wake judgments obtained via accelerometer and sleep diary: a comparison. Behav Res Methods. 2008 Nov;40(4):1026-9. doi: 10.3758/BRM.40.4.1026. PMID: 19001393. 22. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4. PMID: 2748771