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CTRI Number  CTRI/2016/04/006803 [Registered on: 07/04/2016] Trial Registered Prospectively
Last Modified On: 14/04/2018
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Ayurveda 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Management of changes in eye due to diabetes mellitus 
Scientific Title of Study   Effect of Ayurvedic Treatment protocol in the management of Madhumehajanya Timira w.s.r to Diabetic Retinopathy-A Clinical Study 
Trial Acronym  DR 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Prof Manjusha rajagopala 
Designation  Professor and head of department 
Affiliation  Gujrat ayurved university 
Address  DEPARTMENT OF SALAKYA TANTRA I.P.G.T.R.A JAMNAGAR

Jamnagar
GUJARAT
361008
India 
Phone  9428400759  
Fax    
Email  bhatrajma2008@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Prof Manjusha rajagopala 
Designation  Professor and head of department 
Affiliation  Gujrat ayurved university 
Address  DEPARTMENT OF SALAKYA TANTRA I.P.G.T.R.A JAMNAGAR
Krishna Kumar v PhD scholar Department of salakya thantra IPGTRA Jamnagar-361008 Mob . no.9496329408
Jamnagar
GUJARAT
361008
India 
Phone  9428400759  
Fax    
Email  bhatrajma2008@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Prof Manjusha rajagopala 
Designation  Professor and head of department 
Affiliation  Gujrat ayurved university 
Address  DEPARTMENT OF SALAKYA TANTRA I.P.G.T.R.A JAMNAGAR
Krishna Kumar v PhD scholar Department of salakya thantra IPGTRA Jamnagar Mob . no.9496329408
Jamnagar
GUJARAT
361008
India 
Phone  9428400759  
Fax    
Email  bhatrajma2008@gmail.com  
 
Source of Monetary or Material Support  
Institute for post graduate teaching and research in ayurveda Jamnagar-361008 
 
Primary Sponsor  
Name  Institute for post graduate teaching and research in ayurveda gujrat ayurved university 
Address  Institute for post graduate teaching and research in ayurveda Jamnagar 361008 
Type of Sponsor  Research institution and hospital 
 
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 
ProfMANJUSHA RAJAGOPALA  O.p.d. no.4 dept of shalakya thantra  I.P.G.T.R.A hospital Gujarat Ayurved university JAMNAGAR
Jamnagar
GUJARAT 
9428400759

bhatrajma2008@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional ethics committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Patients diagnosed of diabetic retinopathy fulfilling inclusion criteria,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  ANTI HYPER GLYCEMIC ANTI ANTIDR TREATMENT  Group B Control Group Diagnosed cases of DM having DR changes will be included and kept under observation till the whole therapy period They will be continued with their antihyperglycemic and antiDR treatment if any  
Intervention  Durvadi ghrita Rasayana yoga Takradhara  Preparatory Stage Deepana Pachana with Shivakshara Pachana churna or ChitrakadiVati or AmapachanaVati or Panchakola churna or Trikatu churna with luke warm water for five to seven days Kostha Shodhana with Eranda brishta hareetaki or Eranda dashamoola kashaya orDrakshadi kashaya orAvipattikara churna for three to five days at morning time Followed by Shiroshodhanam by Pippali and Saindhava Avapida Nasya Sharangadhara Samhita Uttarakhanda or Shadabindutaila orAnutaila or Sahacharaditaila for seven days According to Prakritri the suitable drug will be selected. For that short Prakriti evaluation proforma will be prepared Treatment phase Marsha Nasya with Durvadi ghrita for seven days at morning or evening time followed by Pratimarshya nasya with same Monthly one sitting Total three sittings Shirodhara by Siddha Takra as medium thirty minutes daily for fifteen days at the morning time monthly one sitting total three sittings Oral Medication Anubhuta Rasayana yoga Dosage Form capsules of five hundred mg or three gm powder Dosage six caps or three gm at bed time for three months Anupana three gm Madhu and six gm ghrita Time of administration at bed time with the advice not to take anything orally for an hour except hot water All the above therapies will be continued along with Antihyperglycemic treatment as advised by the treating physician  
 
Inclusion Criteria  
Age From  30.00 Year(s)
Age To  70.00 Year(s)
Gender  Both 
Details  Patients willing for treatment
Patients having type 1 and type 2 (non insulin depandent) with or without visual disturbances,but the detectable ophthalmoscopic features of DR
Patients of type 1 and type 2 (non insulin dependent) with blood sugar level,FBS-126 to 220 mg/dl or PPBS-186 To 300 mg/dl with ongoing treatment 
 
ExclusionCriteria 
Details  Patients who are extremely debilitating and those who are not able to withstand treatment procedures
Patients of type-1diabetes or type-2diabetes taking insulin
High risk DR Or those requiring emergency intervention
Patients of DR witg media opacity like cataract, vitreous degeneration etc. Which interfere with ophthalmoscopical finding
Patients having other ocular pathologies like glaucoma high myopia etc
Hypertensive retinopathy and DR Associated with pregnancy
 
 
Method of Generating Random Sequence   Random Number Table 
Method of Concealment   Case Record Numbers 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
signs and symptoms of DR will improve with treatment  90 days 
 
Secondary Outcome  
Outcome  TimePoints 
blurring of vision will improve  90days 
 
Target Sample Size   Total Sample Size="100"
Sample Size from India="100" 
Final Enrollment numbers achieved (Total)= "100"
Final Enrollment numbers achieved (India)="100" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   13/04/2016 
Date of Study Completion (India) 04/01/2018 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details
Modification(s)  
1) Pharmacognostical and Phytochemical Analysis of Ingredients Of Siddha Takra - An Ayurvedic Polyherbal Formulation For Takra Dhara In Diabetic Retinopathy, World Journal of Pharmaceutical Research, SJIF Impact Factor 6.805, Volume 5, Issue 7, 1864-1870. Research Article ISSN 2277– 7105. 2) Pharmacognostical and Phytochemical Analysis of Anubhuta Rasayan Yoga-An Ayurvedic Polyherbomineral Formulation For Diabetic Retinopathy, World Journal of Pharmaceutical Research, SJIF Impact Factor 6.805, Volume 5, Issue 7, 1421-1427. Research Article ISSN 2277– 7105. 3) Pharmacognostical and Physicochemical Analysis of Durvadi Ghrita – An Ayurvedic Polyherbal Formulation, World Journal of Pharmaceutical Research, SJIF Impact Factor 6.805, Volume 5, Issue 9, 1242-1251. Research Article ISSN 2277– 7105. 4) Diabetes Mellitus In Ayurveda Wsr To It’s Aetiopathogenesis, International Journal Of Current Research, Vol. 9, Issue, 04, pp.49173-49177, April, 2017  
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary
Modification(s)  

The frame of the present research work entitled Effect of Ayurvedic Treatment protocol in the management of Madhumehajanya Timira w.s.r. to Diabetic Retinopathy-A Clinical Study has been disposed into following sections:

 

1.      Introduction

2.      Conceptual study-Ayurvedic & Modern review

3.      Drug review- Pharmacognostical &Analytical Study

4.      Procedure review

5.      Clinical study

6.      Discussion

7.      Summary and Conclusion

1) Introduction:

In Introduction part, the gravity and incidence of the disease has been discussed. Its hypothesis in Ayurvedic literature regarding concept of the disease, treatment and selection of therapy after reviewing the previous research works done has been explained thoroughly. The plan of study with the selected aims and objectives was also given in brief in this portion. Hypothesis regarding selection of procedures was made upon the facts that in Madhumeha, there is Rakta vitiation due to Kleda and Kapha Vargiya Dravyas causing damage to Rasayanis. Later there will be derangement of Kapha causing Pitta Dushti and further leads to a condition similar to Raktapitta. Based upon this hypothesis Koshtashodhana was adopted. Takradhara which checks bleeding, acts on relieving stress and nourishes the Shira Marma was adopted along with Nasya which is having sense organ stimulant, Srotoshodhaka and Raktapittahara properties. Rasayana Yoga was consisting of all Pramehahara and Chakshushya drugs and was selected on the basis of hypothesis that it affects both Madhumehameha as well as Madhumehajanya Timira.

Aims and objectives

1.      To understand Madhumehajanya Timira in the light of Diabetic Retinopathy – various ocular complications of Diabetes mellitus.

2.      To evaluate the clinical efficacy of the adopted treatment approach in Diabetic Retinopathy

Hypothesis

Null Hypothesis (H0)

The adopted Ayurvedic treatment is not effective in managing Diabetic Retinopathy.

Alternative Hypothesis (H1)

The adopted Ayurvedic treatment is effective in managing Diabetic Retinopathy.

 

2) Conceptual Study:

 

a) Ayurvedic review

 

Madhumehajanya Timira is a Drishtigata Roga. The term Drishti has been used both functionally and structurally in our classics. After a comprehensive review regarding this term, it has been concluded that eyeball as a whole along with structures directly involved in visual process starting with tear film, central cornea, lens, retina as a whole and optic tract can be taken as Drishti with selectivity as per contexts. In Prameha Pidika, Rasayani Daurbalya concept has come which occurs due to Kleda and Kapha Bahulya as well as due to Apana and Vyana Vayu Dushti in the body due to improper/no treatment of Prameha and continuation of etiological factors. Also another fact that Rasayani Daurbalya is present since the starting phase of the disease but manifested as fundus findings later and visual symptoms still later came into consideration while reviewing the literature.

 

On comparing the etiological factors a great similarity between etiological factors of Prameha as well as Netra Rogas were found.  Moreover medieval period book, Netraprakashika has a direct reference of Netra Rogas due to Prameha. By taking all these concepts the study was planned. The modern review of the disease was taken from different text books, peer review journals and internet. The pathogenesis involved in is Rasayani Daurbalya (vascular damage consisting endothelial cell damage, pericyte loss etc.) was analysed in both Ayurvedic and Modern perspectives.

 

 

b) Modern Review

 

As the major structure evident to be involved in Diabetic retinopathy is Retina, due importance has been given to retina and its anatomy has been dealt with in detail. In disease review, detailed description regarding etiology, pathogenesis, classification and treatment have been dealt.

 

3) Drug Review:

 

Drug  review  deals  with  the  detailed  description  of  selected  formulations  i.e.  Drugs of Takradhara, Durvadi Ghrita which was used for Marsa and Pratimarsha Nasya and Rasayana Yoga and the logic/ reason behind the selection of formulations.

 

Under Drug Review, Pharmacognostical as well as Analytical study of the drugs were given in detail with their main physico- chemical parameters.

 

4) Procedure Review:

 

Procedure review introduces the detailed description of selected procedures i.e Koshtashodhana Karma, Shirashodhana, Takradhara, Marsa and Pratimarsha Nasya for the present clinical study.

 

5) Clinical Study:

 

Clinical study section deals with the need and plan of study in detail, aims and objectives, material and methods, criteria for selection of patients in the study and exclusion criteria, Grouping, treatment schedule, assessment criteria and observations in tabular form along with the statistical analysis of results obtained.

1.      The study was approved by Institutional ethics committee letter no. PGT/7 A/Ethics/2015-16/2625 dated 11/12/15.

 

2.      The Clinical trial was registered under CTRI with CTRI No. CTRI/2016/04/006803 registered on 07/04/2016.

 

A Clinical Research Proforma was designed consisting of examination of the patient, various investigations etc. Based on the assessment criteria and observations, the effects and results of the therapy were assessed. The patients were selected by SIMPLE RANDOM SAMPLING METHOD & were divided into 2 groups:

 

Group A: (Trial Group) – 70 patients

 

Group B :( Control Group) – 30 patients

 

 

The study was conducted in black box design.

Inclusion Criteria

Ø  Patients willing for the treatment.

Ø  Patients of 30-70 years having Type 2(Non insulin dependent) diabetes with or without visual disturbances, but with detectable ophthalmoscopic features of DR.

Ø  Patient of Type 2(Non insulin dependent) diabetes with blood sugar level, FBS- 126 to 220 mg/dl or PPBS-180 to 300 mg/dl with ongoing treatment.

Exclusion Criteria

Ø  Patients who are extremely debilitating and those who are not able to withstand treatment procedures.

Ø  Patients of Type-1 Diabetes or the patients of Type-2 Diabetes taking Insulin.

Ø  High Risk DR or those requiring emergency intervention.

Ø  Patients of DR with media opacities like cataract, vitreous degeneration etc. which interfere with ophthalmoscopical findings.

Ø  Patients having other ocular pathologies like glaucoma, high myopia etc.

Ø  Hypertensive Retinopathy and DR associated with pregnancy.

Ø  Patients whose BCVA is less than 6/60

 

 

A total of 100 patients diagnosed to have diabetic retinopathy with symptoms and/or signs were selected for the study. 10 patients dropped out were later excluded from the study. The selected patients were assigned randomly into two groups (A &B), group A having 62 and group B having 28 patients. Each group was subjected to the treatment in the following method.

STUDY DESIGN (GROUPING):

 

Group A: (Treatment Group)

 

Preparatory Stage:

1)                  Deepana Pachana with Shivakshara Pachana Churna/ Chitrakadi Vati/      Amapachana Vati/ Trikatu Churna 5-10 gms/ 1 tablet  with lukewarm water      orally twice daily for 5-7 days according to the Koshta of patients.

2)                  Koshta Shodhana with Eranda Brishta Hareetaki/ Avipattikara Churna -5-10 gms with lukewarm water orally in  morning for 3-5 days according to the Koshta and             Prakriti of patients.

3)                  Shirashodhana with Anu Taila – 8-10 drops into each nostril for 7 days.

 

Treatment phase:

1)         Marsha Nasya with Durvadi Ghrita-8-10 drops into each nostril for 7 days followed by Pratimarsha Nasya with same. Total three sitting of Marsha Nasya was done.

2)         Takradhara by Siddha-Takra as medium 30 minutes daily for 15 days in morning. Total three sitting of Takradhara was done.

 3)        Oral Medication (Anubhuta Rasayana Yoga) - 3 gm at bed time with 3gm Madhu and 6 gm Ghrita.

All the above therapies were continued along with Anti-hyperglycemic treatment as advised by the treating physician.

Group B: (Control Group)

Diagnosed cases of DM having DR changes were included and kept under observation till the whole therapy period. They were continued with their anti-hyperglycemic and anti-DR treatment, if any.

Duration of Therapy and Follow up:

The therapy was continued for 90 days.

Follow up study was done for 1 month at 15 days interval.

The effect of treatment was assessed on the basis of both subjective criteria and objective criteria; since the improvements in both patients’ vision and ophthalmoscopic features are necessary in Diabetic Retinopathy to say if the existing stage of retinopathy regressed or maintained. Specialized scoring pattern for subjective criteria was adopted. Whereas for objective assessment of therapy Best Corrected Visual acuity, Ophthalmoscopy, Fundus photography, Fundus Fluorescein Angiography and Optical coherence tomography was adopted. Laboratory investigations - FBS, PPBS, HbA1C, S. Cholesterol, Hb, S.G.O.T, S.G.P.T, Urea, S.Creatinine and Urine sugar were also taken  for assessment. Results were assessed in terms of percentage relief and statistical evaluations.  

 

  Observations (Demographic data)

 

Maximum number of patients was of age group between 61-70years. Majority of the patients were male i.e. 57(57.00%) and rest patients were female i.e. 43(43.00%). Majority of patients were Hindus i.e. 94(94.00%) and 06(06.00%) patients were Muslim. Majority i.e. 98 (98.00 %) patients were married. 38(38.00%) patients were house wives followed by 25(25.00 %) patients retired. Maximum patients (51.00%) were uneducated. Majority of the patients i.e. 47.00% belonged to middle class. In this study 100.00% belonged to Jangala Desha. Maximum (91.00%) of patients were Vegetarian. Maximum i.e. 84.00% patients were having good appetite. Maximum 82.00% patients were having sound sleep. It was observed that 64.00% were having Mridu Koshta. Maximum (92.00%) patients were having normal micturition. It was observed that 11.00% patients were addicted to Tobacco. It was observed that 84.00% of patients had moderate built. Maximum female patients, i.e 86.04 % were in menopausal period. It was observed that 86.00% were using spectacles. In Aharaja Nidana, 20.00% were having excessive use of curd. In Viharaja Nidana, 15.00 % patients were having mental stress and 15.00 %patients were having day sleeping. Maximum i.e. 66.00% of patients were taking Madhura Rasa dominant diet. Also 55.00% of patients were taking Snigdha Guna dominant diet.

It was observed that 63.00% patients were of Pittakapha Prakriti, 37.00 % patients were of Rajasik Prakriti, 95.00% patients were having Madhyama Satva, 93.00% patients were found to have Madhyama Sara, 95.00 % of patients were having Madhyama Samhanana, 95.00% of patients were having Madhyama Pramana, 95.00% were having Madhyama Satmya, 94.00 % of patients were having Madhyama Ahara Shakti, 92.00   %   of   patients   were   having   moderate exercises, 61.00% were in the Madhyama age group and 95.00% patients were having Madhyama Vikruti.

Observations on Disease.

All (100.00%) of patients were having complaints of diminished vision, followed by 18.00 % of patients having complaints of blurriness of vision. No patients had complaints of frequent changes in presbyopic glasses, perception of flashes of light, floaters and problem for dark adaptation. In this study 95.00% of patients had NPDR, 05.00% had PDR and 04.00% had DME. Majority of patients 73.00% were having dot blot haemorrhages. Superficial Haemorrhages were seen in 49.00 % patients. 60.00% patients were having hard exudates. In the study, 96.00% patients had gradual onset of ocular complaints and 04.00% had sudden onset. In the study 63.00 % were having chronicity of 0-1 year whereas 30.00 % patients were having chronicity of 2 –5 years. Maximum number of the patients, i.e.48.00% was having history of Diabetes up to 5 years. 27.00 %reported onset of Diabetes 6-10 years ago. It was observed that 97.00% patients were having regular control of Blood sugar level. Positive family history was reported in 23.00% and 77.00% had no family history of DM. Also 41.00 % were found to be hypertensive.

 

A detailed description of effect of therapy was given on the basis of subjective criteria, objective parameters and lab investigations. In brief the comparative results of both the groups can be explained like this-

 

a) Comparative Effects in both Groups

 

On Symptoms- On symptoms like defective vision and blurred vision, both the groups had statistically insignificant result.

 

On Signs-Treatment on Group A was more effective in reducing dot-blot haemorrhages, superficial haemorrhages, hard exudates and BCVA.

 

On Lab Parameters- on lab investigations like FBS and S. Cholesterol, Group A was better than Group B whereas on PPBS, Hb, HbA1C and urine sugar both the groups were showing more or less same results which was statistically insignificant. It could also be concluded that there was no statistically significant change in SGOT, SGPT, Urea and S. creatinine in Trial group. Thus there was no change in liver function and renal function tests in patients of trial group after taking Rasayana yoga.

 

b) Overall Effect of Therapy

 

·         In Group A, out of 62 patients, 04 (06.45%) got moderate improvement after the completion of treatment, 23(37.09%) got mild improvement, 35 (56.45%) remained unchanged. No eye showed progression.

 

  • In Group B, out of 28 patients, 02 (07.14%) got moderate improvement after the completion of treatment, 06 (21.42%) got mild improvement, 18 (64.28 %) remained unchanged and 02(7.14 %) showed worsening in condition.
  • Thus it may be concluded that Group A where Ayurvedic treatment were also given with modern-counterpart showed over all better effect.

 

6) Discussion:

 

A detailed discussion was done on selection of disease, conceptual part, and selection of procedures and drug with their probable modes of action, clinical study and effect of therapy on all the selected patients. Some important discussion on results are-

 

 

• Group A (Treatment Group) was effective in reducing dot blot haemorrhages and superficial haemorrhages. This can be said that Group A indicates towards improving health of retinal vasculature in this short duration of treatment with a significant improvement in hemorrhages by reducing the Kleda in blood and improving the other Dushyas, and by virtue of Rasayana Yoga, Takradhara and Nasya the Rasayani daurbalya is countered, thereby the structural health of the body vasculature is strengthened. That’s why no fresh haemorrhage was observed.

 

• Group A was more effective in lowering FBS and S.cholesterol showing that integrated approach in DM gives a better FBS and S.cholesterol control. It is reflecting that treatment by Takradhara, Pratimarsha Nasya and Rasayana therapy after Koshtashodhana in group A was helpful in blood sugar and S. cholesterol control along with its maintenance for a long period.

•                     There was no statistically significant change in SGOT, SGPT, Urea and S. creatinine in Trial group. Thus there was no change in liver function and renal function tests in patients of trial group after taking Rasayana Yoga.

 

Koshtashodhana by virtue of its Kledaharana, Pitta Shodhana, Rakta Prasadana actions; Sirasodhana due to its Urdhwasrota Shodhana effect; Durvadi Ghrita Marsa and Pratimarshanasya by its Rakta Sthambhaka and sense organ rejuvenating properties, Takradhara due to its Raktha Sthambhaka, Kledaharana, Sophaharana and mental relaxant effect and all drugs used in Rasayana yoga by their Chakshushya and Pramehahara properties have their role in combating the pathogenesis of Madhumehajanya Timira DR. Thus by these virtues the holistic Ayurvedic approach is helpful in giving a complimentary treatment protocol to the    DR patients.

 

Secondary outcome of the study: All patients reported betterment in their physical and mental well being which suggests that Holistic approach is improving the Quality of life and vision. Some reported attainment of good sleep following Takradhara which verifies its soothing and mental relaxing effect.

 

Adverse reactions: No adverse reactions were reported in any of the patients during the entire study period and follow up

 

CONCLUSION

 

From the present study following conclusions are drawn:

 

•   Group A (Treatment Group) showed better results on Dot blot haemorrhages, Superficial haemorrhages, hard Exudates, BCVA, FBS and S. cholesterol.

 

•  Both the groups showed almost similar effects in PPBS, Hb , HbA1C and urine sugar which was statistically insignificant.

 

•  There was no statistically significant change in SGOT, SGPT, Urea and S. creatinine in Trial group showing the safety of Anubhuta Rasayana Yoga.

 

•  There was no statistically significant change in symptoms like defective vision and blurred vision in both groups.

 

 

 

The better results in the treatment group(Group A) may be due to the improved health status of whole body vasculature specially microvasculature in retina i.e Rasayanis, which prevented further exudations thereby decreasing retinal oedema leading to improved visual status. Hence the null hypothesis was rejected and alternate hypothesis ie,” The adopted Ayurvedic treatment is effective in managing Diabetic Retinopathy” has been proved.

 
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