CTRI

Research Question- Is there any difference in the efficacy of MadhumehaÌ„riÌ„ cuÌ„rá¹‡a with or without

TriphalaÌ„-Ghá¹›ta Aká¹£itarpaá¹‡a for Non-Proliferative Diabetic-Retinopathy?

HYPOTHESIS

Null Hypothesis (Ho ) - There is no difference in the effect of MadhumehaÌ„riÌ„ cuÌ„rá¹‡a with or without

TriphalaÌ„-Ghá¹›ta Aká¹£itarpaá¹‡a in the management of NPDR.

Alternative Hypothesis (HA ) - There is difference in the effect of MadhumehaÌ„riÌ„ cuÌ„rá¹‡a with or

without TriphalaÌ„-Ghá¹›ta Aká¹£itarpaá¹‡a in the management of NPDR.

AIM

To compare the effects of MadhumehaÌ„riÌ„ CuÌ„rá¹‡a with and without TriphalaÌ„-Ghá¹›ta Aká¹£itarpaá¹‡a in

managing Prameha Upadrava, with a particular focus on its impact on Non-Proliferative Diabetic-

Retinopathy.

OBJECTIVES

1. To validate â€˜PraÌ„yaá¸¥ PradhaÌ„naprasÌame PrasÌamo Bhavatiâ€™ in Prameha Upadrava with

special reference to Non-Proliferative Diabetic-Retinopathy.

2. To evaluate the efficacy of MadhumehaÌ„riÌ„ CuÌ„rá¹‡a in Non-Proliferative Diabetic-Retinopathy.

3. To evaluate the efficacy of MadhumehaÌ„riÌ„ CuÌ„rá¹‡a with TriphalaÌ„-Ghá¹›ta Aká¹£itarpaá¹‡a in Non-

Proliferative Diabetic-Retinopathy.

4. To compare the effect of MadhumehaÌ„riÌ„ CuÌ„rá¹‡a with or without TriphalaÌ„-Ghá¹›ta Aká¹£itarpaá¹‡a in

prameha upadrva with special reference to Non-Proliferative Diabetic-Retinopathy.

PLAN OF STUDY

Material And Methods: Literary references will be collected from ayurveda classics, commentaries,

modern literature, research journals, Thesis &other related documents.

The whole study will be composed of following Three phases.

1. Preparation of Drug

2. Quality control analysis of Drug

3. Clinical study

1.Preparation of Drug- The Drugs MadhumehaÌ„riÌ„ CuÌ„rá¹‡a and TriphalaÌ„-Ghá¹›ta will be prepared in

GMP certified Pharmacy of NIA. by means of classical methods.

Composition Of MadhumehaÌ„riÌ„ CuÌ„rá¹‡a

S.No. Drug Name Botanical Name Used Part Part Ratio

1. JambuÌ„ Syzygyum cumini Seed 1 Part

2 AmrasthiÌ„ Mangifera indica Seed 1 Part

3 Karavallaka Momordia charantia Fruit 1 Part

4. Mesha shringiÌ„ Gymnema sylvestra Leaves 1 Part

5. MethikaÌ„ Trigonella foenum Seed 1 Part

6. Bilva Aegle marmelos Leaves 1 Part

7 Nimba Azadirachta Indica Dry Seed 1 Part

8. Svarna patri Cassia agustifolia Leaves 1 Part

9 Shatapushpa Foeniculum vulgare Seed 1 Part

10 BalaÌ„ Sida cordifolia Seed 1 Part

11 Babbula Acacia arabica Fruit 1 Part

12 ShunthiÌ„ Zingiber officinale rosc. Rhizome 1 Part

Route of administration - Orally

Dose - 6gm

Dose form - CuÌ„rá¹‡a

Anupana - Luke warm water

Time of administration - Twice in a day, Before meal

Total Duration of drug intake - 45 days

Method of preparation of MadhumehaÌ„riÌ„ CuÌ„rá¹‡a: As per standard protocol in GMP certified NIA

pharmacy [Nageshwar Rasayanshala]. All 12 Medicines will be taken in 1 Part each. Then these

ingredients are grinded finely to prepare a powder.

Composition Of TriphalaÌ„-Ghá¹›ta

Sr. No. Name of Drugs Botanical Name Useful Part Part ratio

1 HaritakiÌ„ Terminalia Chebula Geartn. Fruit 1 Part

2 VibhitakiÌ„ Terminalia Bellirica Geartn. Fruit 1 Part

3 AmalakiÌ„ Emblica Officinalis linn. Fruit 1 Part

â€˜Route of administration-Local Application

Dose â€“2oml in each affected eye

Dose form-Ghá¹›ita kalp

Time of administration -Morning time Between 10AM-12AM

Total Duration â€“ 20 day with gap of 10 days in each sitting

Method of preparation of TriphalaÌ„ Ghá¹›ta

As per standard protocol in GMP certified NIA pharmacy [Nageshwar Rasayanshala]. TriphalaÌ„ (fruits

of HariÌ„takiÌ„,VibhiÌ„takiÌ„ And AÌ„malakiÌ„) are taken in amount of 32 tolaÌ„ cooked with 1 AÌ„á¸aka Jala , boil it

and reduce it till Â¼ water remains and filter it. Take 1 Prastha cow milk, 1 Pala TriphalaÌ„ kalka, Â½

Prastha cow ghee and cooked it.

when ready, filter it.

2.Quality control analysis of Drug -Colour, Odor, Rancidity, Specific Gravity, pH Value ,Loss on

drying at 105 Celsius, Refractive index , Viscosity , Iodine Value ,Saponification Value , Unsaponified

matter , Acid Value ,Peroxide Value Free Fatty acid , Total fatty matter , High-Performance Thin-

Layer Chromatography (HPTLC) ,Test for heavy /Toxic metals , Microbial Contamination , Specific

Pathogen Testing, Shelf-Life Assessment .

3.Clinical Study

Following material &method will be employed for conducting the present research work. The study

will be conducted under a strict protocol to prevent bias and to reduce the source of error in the study.

A) Case Selection:

40 registered Clinically Diagnosed patients of Non proliferative diabetic retinopathy grade I &

fulfilling the inclusion criteria will be randomly selected from OPD and IPD of Dept. of

Shalakya and Madhumeha unit of Samhita dept of NIA Jaipur, Rajasthan. Patients will be

selected irrespective of caste, religion, nationality, socioeconomic status.

Age group: Patients in the age group of 35-70years will be selected for the study.

Number of Cases: 40 patients (20 in each group).

B) Calculation of sample size

Selection of study sample will be based on specific inclusion criteria. The initial sample size was

calculated using Open EPI software. However, due to budget constraints, conducting the study with

the originally calculated large sample size is not feasible. Therefore, the study will proceed with a

smaller sample size of 40 participants, evenly divided into two groups, with 20 patients in each group.

C) Inclusion Criteria:

Patients of either sex in the age group of above 35 years and below 70 years irrespective of

sex, race, religion, and socio-economic status.

Patient suffering from Diabetic retinopathy with the clinical feature of Non proliferative

diabetic retinopathy (Mild to moderate).

HbA1c Levels: Patients with a known diagnosis of Type II diabetes mellitus and HbA1C levels

6.5- 8 %

Visual Acuity: Visual acuity should range from 6/60 to 6/9.

Central Retinal Thickness (CRT) at OCT: Must be greater than 400 microns and less than 600

microns.

Ocular Condition: Clear ocular media and sufficient pupillary dilatation to enable fundus

imaging.

Diabetic Macular Oedema (DME): Clinically significant DME with a duration of less than 12

months.

D) Exclusion Criteria:

Patient received anti-VEGF treatment within the previous 12 months.

Patients with visual impairments like Macular degenerations, Retinitis Pigmentosa.

Patients with, Mature Cataract, post Cataract surgeries, Glaucoma etc.

Patient suffering systemic illness which may cause visual impairment.

Patients with known allergies to any components of the proposed treatment should be

excluded.

Known Drug Interactions: Patients taking medications with known interactions with the

proposed treatment should not be included.

Participation in Other Clinical Trials: Patients who are currently participating in other clinical

trials should be excluded to avoid potential confounding factors.

Cognitive Impairment: Patients with severe cognitive impairments that hinder their ability to

understand and follow the treatment plan should be excluded.

E) Patient Grouping:

In the present study 40 clinically diagnosed patients of Non proliferative diabetic retinopathy

(Pramehajanya Timira) will be selected and randomly divided into two groups (20 patients in each

group):

Posology -

Group A â€“ All 20 patients advised to take 6 gm MadhumehaÌ„riÌ„ CuÌ„rá¹‡a twice a day for 45 days

regimen.

Group B â€“ 20 patients have been advised to follow the following treatment regimen for a total

duration of 45 days:

Step 1: For the first 3 days, undergo Dipana PaÌ„cana with citrakaÌ„di vati.

Step 2: For the next 3 days, Anulomana with Eraá¹‡á¸a bhá¹›sta haritaki powder.

Step 3: In the subsequent 3 days, perform Nasya with Anu tail.

Step 4: After completing the Nasya with anu taila,patient undergo Aká¹£itarpaá¹‡a with TriphalaÌ„

ghá¹›ta. This will be done in three sittings, each lasting for 5 days, with a 10 day interval

between each sitting. This comprehensive treatment plan spans a total of 45 days and aims to

address the health concerns of the patients.

Along with this regime take 6 gm MadhumehaÌ„riÌ„ CuÌ„rá¹‡a .

Follow Up Period:

Follow up will be done on 15 th day & 30 th day..

F) Study Design:

Study Type : Randomized Clinical study, Interventional

Purpose : Treatment

Masking : Open label (No blinding /No masking)

Timing : Prospective

No. of Groups : 2 Groups

No. of patients : 40

Duration of therapy : 45 days

ASSESSMENT CRITERIA FOR DIABETIC RETINOPATHY:

A. Subjective Parameters for Vision Assessment:

Vihwala Drishti (Blurred vision)

Makshika Mashaka Kesha Jaala Pashyati (Floaters)

Nasa Akshi Yuktani Vipritani Vikshate (Metamorphopsia - Distorted images)

Tamasa Darshanam (Perception of black spots/Scotoma) etc.

B. Objective Parameters for:

Detecting microaneurysms

Identifying hard and soft exudates

Assessing haemorrhages

Measuring visual acuity / best-corrected visual acuity (BCVA)

Macular thickness measurement

Vihwala Drishti(Blurred vision)

Grade 0 No blurred Vision

Grade 1 Blurred vision but without imitating (inhibiting) Activities

Grade 2 Sometime difficulty in performing routine work

Grade 3 Unable to go out independently

Makshika Mashaka Kesha Jaala Pashyati(Floaters)

Grade 0 No perception of floaters

Grade 1 Occasionally interfering with routine work.

Grade 2 Regularly interfering with routine work.

Grade 3 Canâ€™t perform routine work

Nasa Akshi Yuktani Vipritani Vikshate (Metamorphopsia - Distorted images)

Grade 0 No perception of distorted images

Grade 1 Occasionally interfering with routine work

Grade 2 Regular interference with routine work

Grade 3 Unable to perform routine work

Tamasa Darshanam (Perception of black spots/Scotoma)

Grade 0 No perception of black spot

Grade 1 Occasionally interfering with routine work

Grade 2 Regular interference with routine work

Grade 3 Unable to perform routine work

Microaneurysm Detection

Grade 0 No microaneurysms detected

Grade 1 Microaneurysms present in 1 Quadrant.

Grade 2 Microaneurysms present in 2 Quadrant.

Grade 3 Microaneurysms present in 3 Quadrant

Identification of Hard Exudates

Grade 0 No hard and soft exudates present

Grade 1 A few hard and soft exudates present in any of the quadrants

Grade 2 A few hard and soft exudates present in two quadrants.

Grade 3 A few hard and soft exudates present in 3 quadrants

Intraretinal Hemorrhage Assessment

Grade 0 Absent Bleeding

Grade 1 Hemorrhage present in 1 Quadrant

Grade 2 Hemorrhage present in 2 Quadrants

Grade 3 Hemorrhage present in 3 Quadrants

Visual Acuity / Best Corrected Visual Acuity (BCVA)

Visual acuity is graded using the Logarithm of the Minimum Angle of Resolution (Log MAR) scale

for analysis purposes. On the Log MAR scale, better visual acuity is represented by lower values, and

worse visual acuity is represented by higher values.

Snellenâ€™s test type:

Distant vision chart testing Log MAR value

6/60 1.0

6/36 0.778

6/24 0.602

6/18 0.477

6/12 0.401

6/9 0.176

6/6 0

Near vision and best corrected visual acuity were tested by using Jaegerâ€™s Chart.

Near vision chart testing Log MAR value

N/5 0

N/6 0.097

N/8 0.176

N/10 0.401

N/12 0.398

N/14 0.477

N/18 0.602

N/24 0.699

N/36 1

Central macular thickness measured by 3D-Macula OCT Topcon.

Grade 0 Central macular thickness less than 400 Î¼m

Grade 1 Central macular thickness between 400 Î¼m - 400 Î¼m

Grade 2 Central macular thickness between 400 Î¼m - 500 Î¼m

Grade 3 Central macular thickness between 500 Î¼m - 600 Î¼m

Investigations-

FBS, PPBS, HbA1c, LFT, KFT, Urine R&M, OCT, Fundus image.

Investigation will be carried out before and after treatment for the purpose of assessing the effect of

therapy, general condition of the patients and to exclude other pathology.

CRITERIA FOR WITHDRAWAL:

1. During trial if any serious condition or any serious adverse effect occurs that requires urgent

treatment.

2. Patient himself wants to withdraw from the clinical trial.

ADVERSE DRUG REACTION: Any adverse effect of trial drug is not anticipated but if any

harmful, unintended effect of medication occurs, the patient will be assisted and managed with the

help of Allopathic Physicians appointed in NIA, Primary Health Care Unit.

OUTCOMES AND MEASUREMENTS WITH DURATION:

(Time frame baseline to end of 45th day)

Primary outcome: Changes in Features of Non proliferative diabetic retinopathy in ETDRS Score.

Secondary outcome: Changes in the clinical symptoms of Non proliferative diabetic retinopathy.

STATISTICAL ANALYSIS:

Results of the treatment will be recorded, tabulated and analysed statistically with relevant tests and

level of significance will be reported. Drawn conclusions and will be submitted in the form of

dissertation.

For subjective parameters:

a. Intragroup: Wilcoxon paired signed rank test.

b. Inter group: Mann Whitney â€˜Uâ€™ test and

For objective parameters

a. Intragroup: Student paired â€˜tâ€™ test

b. Inter group: Unpaired â€˜tâ€™ test

ETHICS

Informed consent:

Prior to all trial-related procedures, including physical examination, screening, and laboratory studies,

each participant will provide informed written consent. Participants will receive comprehensive

information about the study, including a description of any potential risks and discomforts that may be

foreseen. Additionally, they will be made aware of their right to withdraw from the study at any time

without the obligation to provide reasons.