Effect Of Unani Polyherbal Formulation On Ziabetus Sukari ( Type Ii Diabetes Mellitus ) A Randomized Controlled Clinical Trial

PROTOCOL

EFFECT OF UNANI POLYHERBAL FORMULATION ON ZIABETUS SUKARI

( TYPE II DIABETES MELLITUS ) A RANDOMIZED CONTROLLED CLINICAL

TRIAL

PHASE OF INVESTIGATION : (CLINICAL TRIAL)

INTERVENTIONAL DRUG : UNANI POLY HERBAL FORMULATION AND

METFORMIN

TRIAL REGISTRY: TRIAL WILL BE REGISTERED IN CTRI

CLINICAL LABORATORIES: CLINICAL LABORATORY,

ARINGNAR ANNA GOVERNMENT HOSPITAL OF INDIAN MEDICINE, ARUMBAKKAM, CHENNAI-106.

INTRODUCTION

Ziabetus Sukari ( Type II Diabetes mellitus) is a syndrome of multiple etiologies characterized by chronic hyperglycemia with disturbance of carbohydrates fat and protein metabolism.[1] Diabetes mellitus is currently classified based on the pathogenic process that leads to hyperglycemia. Type 1 Diabetes mellitus is characterized by insulin deficiency and tendency to develop ketosis- it is commonly caused by autoimmune destruction of the pancreatic beta cells. Type 2 Diabetes mellitus is a heterogeneous group of disorders characterizes by variable degrees on insulin resistance, impaired insulin secretion and excessive hepatic glucose production- it is strongly associated with obesity.[2]

Diabetes has emerged as one of the most serious and common chronic diseases of our times, Ibn sina in his book Canon of medicine states that the condition of patients with Diabetes is like where the patient takes water and it is not being retained and held and gets excreted immediately by the kidneys and he named it as Zalakhul kulliya. He mentioned the cause of disease as zayakhoomus, Qaramees, Duwarara and Dulaab and he mentioned other the cause of disease is Zauf e Kulliya (decreased physiological function of kidneys), Gurdon ke

mujariyon ka phailjana ( dilatation of openings or ducts in kidney.[3]

PREVALENCE

Using logistic regression and the attributable fraction approach, a study involving 2019 data sources from 2005 to 2020, representing 215 nations, identified estimates of the prevalence of diabetes. The population projections for 2045 were adjusted using the 2021 estimations.

India has experienced a large increase in noncommunicable diseases in the past several decad es, and now has the second greatest number of people with diabetes in the world at 77 million individuals. This number is expected to increase to over 101 million people with diabetes in the next 10 yrs.[4]

STASTIICAL CONCLUSION:

*N= r+1(Z42+ Z1-13)2**δ2/*rd2

r=1 Z1-13= 0.84

Z42= 1.96

d2= 693.7956

δ2= 1476.0964

N= 1+1(1.96+0.84)2×1476.0964

1×693.7956

= 2× 7.84× 1476.0964

1×693.7956

=33.36

=~33

Taking 20% dropouts

I.e., 6.6~7

Total sample size = 33+7= 40

I.e 30 pts in test group

10 pts control group

AGE STANDARDIZED PREVALENCE:

The prevalence of diabetes among adults aged 20 to 79 over the world was predicted to be

10.5% (536.6 million) in 2021 and 12.2% (783.2 million) in 2045. Diabetes prevalence was comparable between genders and was highest in people aged 75 to 79. In 2021, prevalence was predicted to be higher in urban (12.1%) than rural (8.3%) locations and high-income (11.1%) than low-income (5.5%) nations. Between 2021 and 2045, middle-income countries are predicted to experience the largest relative increase in the prevalence of diabetes (21.1%), followed by high-income (12.2%) and low-income (11.9%) nations.[4]

LONG TERM CONSEQUENCES:[5]

Ziabetus sukari ( Type II Diabetes Mellitus ) leads to long-term complications affecting organs such as eyes, kidney, nerves, heart, and blood vessels.

CLINCAL FEATURE:[6]

Polyuria

Polydipsia

Polyphagia

Weight loss

Tiredness

AIM AND OBJECTIVE

AIM:

The aim of the study to evulate the effect of unani polyherbal formulation in ziabetus sukari (Type 2 Diabetes Mellitus) in the form of Qurs.

OBJECTIVE: To Monitor Fasting blood sugar and 2hour plasma Glucose after intervention

To Monitor HbA1c level after intervention

LITERATURE REVIEW:

Ziabetus (Diabetes, derived from the Latin word "diabetes," originated from the Ancient Greek word "diabainein," meaning "to pass through." The term was first recorded in English in 1425. The term "mellitus" was added in 1675 by Thomas Willis, who noticed a sweet taste in diabetic urine. Diabetes was linked to renal ailment, with a weak quwwat e-mughayyarah potentially contributing to the condition. Ibn Sina/Avicenna referred to the disease as "Dulab," separating diabetes-related polyuria and emaciation from other causes. Long-term diabetes damages the liver, causing profound lassitude, asthenicity, and an aged aspect.[7]

Classification of ziabetus According To Classical unani literature [8]

Ziabetus is of types

Ziabteus Haar ( Shakari)

Ziabetus Barid ( Sada)

On the basis of presence of sugar in urine Ziabetus is divided into two types [9]

Ziabetus Sukari ( Diabetus Mellitus)

Ziabetus Sada ( Diabteus Insipidus)

Etiopathogenesis Described in the Classical Unani Literature by some Unani physicians like Majoosi, Ibn Sina and Samarqandi are as follows.

1. Zaufe Gurda (Weakness of Kidney)

2. Ittesae Gurda wa Majrae Baul (Dilatation of Kidney and tubule).

3. Buroodate Badan, Jigar wa Gurda.

4. Sue Mizaj Haar Gurda (Hot derangement in temperament of kidney).

5. Sue Mizaj Barid Gurda (Cold derangement in temperature in kidney.

Usul -i-ilaj (Principles of treatment): [10]

Taskin - Atsh (Quenching of thirst)

Tabrid (To cool the affected organs)

Tartib i Badan (To enhance moistness in the body)

Ziabetus sukari (type II diabetes mellitus) is currently one of the fastest growing health emergencies in the world.

Of the national and economic burden of this disease, as well as the challenges associated with managing the daily health needs of diabetic patients. Lifestyle modifications and treatment with hypoglycemics, antihyperglycemic, insulin sensitizing, and insulin secretion enhancing agents can lead to significant improvements in diabetic patients. However, the use of these therapeutic regimes is often accompanied by side effects.[11]

In unani system has several compound medicine which has been in use yrs together observed no side effects,so far for ziabetus sukari ( Type II Diabtes Mellitus) eg , Qurs e Diabetes, Qurse

e Kafoor, Qurse gulnar, Qurse Tabasheer, Safoof Ziabetus, Jawarsih Zarooni sada.[9]There are numerous single medications as well, eg tukhm-e- Hayat , Jamun , Gurmar boti, Hulba/methi,Asghand, Maghz-e- neem .[12, 13]

Broader societal processes such as urbanization and globalization, along with dietary changes and declining physical activity, have been primary drivers of the diabetes epidemic in low- and middle-income countries such as India and China. The risk of developing diabetes is dependent on both modifiable factors (e.g., lack of physical activity and obesity) and non-modifiable factors (e.g., age and family history of diabetes). Diabetes carries a large economic burden due to disability and death from several complications, including retinopathy, kidney failure, and heart disease, among others. The long-lasting pathology of disease complications can have severe impacts on individuals, families, communities, and healthcare systems. Individuals with diabetes from families of low socioeconomic status, who already face financial hardships, often spend as much as 60% of their household income to care for family members with diabetes [2].The Unani system of medicine, which has been in use since 460 BC, provides classical treatment modalities and drugs for a variety of diseases. One such unani compound formulation is mentioned in Kitb-al-Hawi, which has been prescribed in Unani literature for the management of Ziabetus sukar (TYPE II Diabetes Mellitus).[14]

RATIONALE[15,16]

S.No

Ingredients

Scientific Name

Pharmacological Activity

Active Ingredient

| |1

GUL E NAR

Punica granatum

Leucorrhoea,

Premature ejaculation,

Spermatorrhoea, Stomatitis,

Haemorrhoids,

Prolapse rectum [15,16]

Alkaliods,

Tannins,

Flavonoids, Glycosides,[17]

|2

GUL- E-

SURKH

Rosa damascene

Anti - inflammatory, Anitidiabetic activity purgative, Laxative.[15,16]

α- Glucosidase[18]

|3

ACACIA

Acacia Arabica Wild

Cough,

Leukorrhea, Syphilis,

Spermatorrhoea,

Diarrhoea,

Anti-inflammatory,

Sore throat.[15,16]

Amino acids, Tannins,

D-galactose

L-arabinose[19]

|4

ACACIA

GUM/ OR

BABUL GUM

Acacia Arabica Wild

Dysentery, Haemostasis,

Epistaxis,

Conjunctivitis,

Diarrhoea,

Menorrhagia [15,16]

Saponins,

Phenolics, Flavonoids[20]

SOURCE OF DRUGS

The required raw drugs will be procured from a well reputed indigenous raw drug shop.

The raw drug (mineral) taken for study will be authenticated by the Department Ilmul Advia at Government Unani Medical College, Chennai.

PREPARATION:

Drugs from the market are dried, finely ground to powder, while acacia is separately ground and mixed with the powder.

DRUG STORAGE:

The trial medicine will be stored in clean, dry, airtight container and it will be dispensed in a labelled container.

INTERVENTION:

Group A: ( Unani poly herbal formulation Kitab ul Hawai 10th volume page no (185)

Drug : Unani polyherbal formulation (Qurs)

Dosage: 2qurs Twice a day (2-0-2)

Duration: 45days (0 , 15, 30, 45)

Group B:

Tab: Metformin 500mg 1-0-1

Aim and Objective

Biochemical analysis of FBS and PPBS with monitor in values

INCLUSION CRITERIA

Age: 30 to 60

Sex: Both Gender

Fasting blood sugar (FBS) >126 mg/dl- < 200mg/dl

2hr Plasma Glucose (2PG)  > 200 mg/dl - <300 mg /dl

HbA1c > 6.5 - < 9.0%

Those who have not taken antidiabetic drugs after diagnosis/ discontinued the medication in the past 3 months.

EXCLUSION CRITERIA:

Fasting blood sugar (FBS) > 200mg/dl

2hr Plasma Glucose (2PG) > 300mg/dl

Known cases of Type 2 Diabetes Mellitus with comorbidities

Pregnant & lactating Women.

History of any systemic illnesses

Known Alcoholic patients.

WITHDRAWAL CRITERIA

Intolerance to the drug and development of any serious adverse effect during trial.

If ADR is reported, the patient will be directed to peripheral Pharmacovigilance Centre.

Poor compliance leads to any disease.

Any other acute illness which needs a rescue medication

STUDY TYPE

: Randomized Controlled Clinical Trial Study

|STUDY PLACE

: Aringar Anna Govt Hospital of Indian Medicine attached with GUMC, Chennai.

|STUDY PERIOD

:18 months

|SAMPLE SIZE

: 40 patients (OP & IP)

Criteria for the screening and diagnosis diabetes [19]

Prediabetes

Diabetes

|HbA1C

5.7% - 6.4% mmol

 6.5% mmol

|Fasting Blood sugar

100 - 125 mg/ dl

126 mg/d/

|2- Hour plasma glucose

140 - 199 mg/ dl

200mg/dl

|Random Blood sugar

 200mg/d/

INVESTIGATION

ROUTINE TESTS

BLOOD INVESTIGATION:

1. Complete blood count

2. Blood urea, serum creatinine

3. SGOT, SGPT, Serum alkaline phosphate

URINE TEST: 1. Albumin

2. Sugar

3. Deposits

SPECIFIC INVESTIGATION

Fasting Blood glucose

2hour plasma glucose

HBA1C

Pre investigation and post investigation:

1. Complete blood count

2. Blood urea, serum creatinine

3. SGOT, SGPT, Serum alkaline phosphate

4. Hba1c

URINE TEST: 1. Albumin

2. Sugar

3. Deposits

Base line investigation for every follow up

Fasting and post prandial blood glucose

UNANI ASSESSMENT AND INVESTIGATION:

UNANI ASSESSMENT:

Parameters

DAMVI

(Sanguine)

BALGHAMI

(Phlegmatic)

SAFRAVI

(Bilious)

SAUDAVI

(Melancholic)

|Complexion

Ruddy (Reddish/Brown)

1

Chalky (Whitish)

.75

Pale (Yellowish)

.5

Purple (Black)

.25

|Build

Muscular & Broad

1

Fatty & Broad

.75

Muscular & Thin

.5

Skeletal

.25

|Touch

Hot & Soft

1

Cold & Soft

.75

Hot & Dry

.5

Cold & Dry

.25

|Hair

Black & Lusty,

Thick, Rapid Growth

1

Black &

Thin,

Slow

Growth

.75

Brown & Thin, Rapid Growth

.5

Brown &

Thin,

Slow

Growth

.25

|Movement

Active

1

Dull

.75

Hyperactive

.5

Less Active

.25

|Diet (Most

Liked)

Cold & Dry

1

Hot & Dry

.75

Cold & Moist

.5

Hot & Moist

.25

|Weather (Most

Liked)

Spring

1

Summer

.75

Winter

.5

Autumn

.25

|Sleep

Normal

(6-8 hrs.)

1

In Excess

.75

Inadequate

.5

Insomnia

.25

|Pulse

Normal (70-80/min)

1

Slow (60-70)

.75

Rapid (80-100)

.5

Slow (60-70)

.25

|Emotions

Normal

1

Calm & Quiet

.75

Angry

.5

Nervous

.25

Total=

Range of temperament numbers:

Sanguine: 7.5 – 10 Phlegmatic: 5.10 – 7.50 Bilious: 2.51 – 5.00 Melancholic: 0.00 – 2.50

Damavi  Balghami:Safravi saudavi

Socioeconomic status scale of kuppuswamy ( Urban 1976)

Parameters Score

|Education

|Professional 7

|Graduate 6

|Intermediate diploma 5

|High school 4

|Middle school 3

|Primary School 2

|Illiterates 1

|Occupation

|Professional 10

|Semi – Professional 6

|Clerical / shop / farmer 5

|Skilled Worker 4

|Semi – Skilled Worker 3

|Unskilled Worker 2

|Unemployed 1

|Family income per month (Rs.)

|>2000 10

|1000 -1999 6

|750 - 999 5

|500 - 749 4

|300 – 499 3

|101 – 299 2

|< 100 1

|Total Score Socioeconomic class

|26 – 29 Upper (I)

|16 – 25 Upper middle (II)

|11 – 15 Lower middle (III)

|5 – 10 Upper lower (IV)

|< 5 Lower (V)

OUTCOME OF TREATMENT

Primary outcome will be predominantly assessed by:

ETHICAL ISSUES

The trail will be registered in CTRI

Informed consent will be obtained from the patients after explaining about the clinical trail in the regional language

Above the consent of the patient (through the consent form ) if the fit in the criteria they will be enrolled in the study.

Treatment will be provided for free of cost

Concomitant medicine will be used if there’s any need

The patient who are excluded (as per the exclusion criteria ) are given proper treatment

With full care at OPD.

DATA COLLECTION FORMS

Required information will be collected from each patient by using following forms:

Form I : Screening and selection Proforma

Form II : History taking proforma

Form III : Clinical assessment proforma

Form IV : Laboratory Investigation proforma

Form V : Informed consent form

Form VI : Withdrawal form

Form VII : Patient information sheet

Form VIII : Adverse drug reaction reporting sheet

CONCLUSION

As the literary evidence support the usage of drugs in the disease, a hypothesis is created such a way that ZIABETUS SUKARI (TYPE 11 DIABETUS MELLITUS) will be effectively treated with UANI POLY HERBAL FORMULATION IN THE FORM OF QURS AND TAB. METFORMIN and hence permission may be granted.

Date:

Stations

Signature of the Guide Signature of the Investigator

REFERENCES

CMR GUIDELINES FOR MANAGEMENT OF TYPE 2 DIABETES 2018 Indian Council of Medical Research, Ansari Nagar, New Delhi-110 029 ICMR Guidelines for Management of Type 2 Diabetes 2018 ICMR GUIDELINES FOR MANAGEMENT OF TYPE 2 DIABETES 2018. (n.d.).

Jameson, J. L., Kasper, D. L., Fauci, A. S., Hauser, S. L., Longo, D. L., & Loscalzo, J. (n.d.). Harrison’s principles of internal medicine, 20e: Vol. II. :McGraw-Hill Education.

Ibn Sina.Al-Kanoon Fil Tibb, (Urdu Translation by Kantoori G H) Vol (3), Idara Kitabul

Shifa, Kucha Celan, Daryaganj, New Delhi .2007, Page: 1031-1033]

IDF Diabetes atlas global estimates of diabetes prevalence for 2107 between 2045.

[Quraishi, Haider Ali, et al. "DIABETES IN CONTEXT OF UNANI SYSTEM OF MEDICINE: A REVIEW STUDY." diabetes 3 (2018): 4.]

Hakim Ajmal Khan Institute for Literary and Historical Research in Unani Medicine Central Council for Research in Unani Medicine Ministry of AYUSH, Government of India 2016

Chaudhury, A., Duvoor, C., Reddy Dendi, V. S., Kraleti, S., Chada, A., Ravilla, R., Marco, A., Shekhawat, N. S., Montales, M. T., Kuriakose, K., Sasapu, A., Beebe, A., Patil, N.,

Musham, C. K., Lohani, G. P., & Mirza, W. (2017). Clinical Review of Antidiabetic Drugs:

Implications for Type 2 Diabetes Mellitus Management. Frontiers in Endocrinology,

8.[ Dr. Reesha Ahmed, Role of some unani single drugs in the treatment of Diabtes melltius type 2 (2017) ]

Firdaus, S., Anwar, A. I., Khan, A. A., & Ahmed, S. (2022). Classical Review of Ziabetus (Diabetes) in Unani Treatise with insightful perspectives of Preventive Measures.

Hakim Ajmal Khan Institute for Literary and Historical Research in Unani Medicine Central Council for Research in Unani Medicine Ministry of AYUSH, Government of India 2016

Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., Peters, A. L., Tsapas, A., Wender, R., & Matthews, D. R. (2012). Management of hyperglycaemia in type 2 diabetes: A patient-centered approach. Position statement of the american diabetes association (ADA) and the european association for the study of diabetes (EASD). Diabetologia 55(6). https://doi.org/10.1007/s00125-012-2534-0

Ahmed, R., Khan, N. A., Khan, B. D., & Waseem, M. ROLE OF SOME UNANI SINGLE DRUGS IN THE TREATMENT OF DIABETES MELLITUS TYPE-2: A REVIEW.

Rauf, A., & Khalique, A. (2019). Unani Herbal Drugs: A Ray of Hope for the Management of Diabetes

Mellitus. Journal of Integrated Community Health (ISSN 2319-9113), 8(2), 21-26.

[Rhazi, Z. "Kitab Al Hawi Fit Tibb." Vol-10. Published by CCRUM New Delhi 241 (2002): 185.]

Ghani Najmul khazayinul Adviya jadeed Idara kitabus Shifa, New delhi (2005) page, 254, 272, 340, 1135.

Iftekharul Mufradat “Hakim shakeeb ahmed”. Published by Ausadh Ghar Iftekharia publication 31, A.P.C Road Kolkata 700009 (2010)

Khanam, T., Siddiqui, N., & Yasir, M. (2018). PHARMACEUTICAL ANALYSIS OF GULNAR FARSI (Punica granatum LINN.)

Ansari, S., Zeenat, F., Ahmad, W., & Ahmad, I. (2017). Therapeutics and pharmacology of Gul-e-Surkh (R osa damascena Mill): An important Unani drug. Int J Adv Pharm Med Bioallied Sci, 3, 195-205.

Anjum, N., Akhtar, J., Bashir, F., & Parveen, S. (2018). PHARMACOLOGICAL INVESTIGATIONS ON AQAQIA – Acacia arabica (Lam.) Willd.

Ashour MA, Fatima W, Imran M, Ghoneim MM, Alshehri S, Shakeel F. A Review on the Main Phytoconstituents, Traditional Uses, Inventions, and Patent Literature of Gum Arabic Emphasizing Acacia seyal. Molecules. 2022 Feb 9;27(4):1171. doi: 10.3390/molecules27041171. PMID: 35208961; PMCID: PMC8874428.