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CTRI Number  CTRI/2021/01/030404 [Registered on: 12/01/2021] Trial Registered Prospectively
Last Modified On: 11/01/2021
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug
Unani 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Effect of Unani formulation in Ring worm 
Scientific Title of Study   Therapeutic evaluation of Topical Halela Zard in treatment of Quba (Tinea Corporis) - A randomised Standard Controlled Trial 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
Nil  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  SUMAYYATASNEEM PARAPUR 
Designation  PG Scholar  
Affiliation  Luqman unani medical college, hospital and research center 12 naubag Vijaypur 
Address  Department of OPD Moalejat ground floor Luqman Unani Medical College, Hospital and Research Center 12 Navbag Vijaypur 586101
Department of OPD Moalijat ground floor, Luqman Unani Medical College Hospital 12 Navbag Vijaypur 586101
Bijapur
KARNATAKA
586101
India 
Phone  7019622214  
Fax    
Email  drsumaiyyatasneem@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Mohd Khalid 
Designation  Assistant professor 
Affiliation  Luqman Unani Medical College 
Address  Dept. of Moalajat, Luqman Unani Medical College Hospital and Research Center, 12 Navbagh

Bijapur
KARNATAKA
586101
India 
Phone  9916261251  
Fax    
Email  khalidhameedkhan@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Nazim Husain 
Designation  Assistant professor 
Affiliation  Luqman Unani Medical College Hospital and Research Center 
Address  Dept. of Moalajat, Luqman Unani Medical College Hospital and Research Center, 12 Navbagh

Bijapur
KARNATAKA
586101
India 
Phone  9212143572  
Fax    
Email  dr.nazimhusain@gmail.com  
 
Source of Monetary or Material Support  
Luqman Unani Medical College Bijapur 
 
Primary Sponsor  
Name  Luqman Unani Medical College Hospital and Research Center Vijaypur 
Address  12 Navbag Vijaypur 586101 Karnataka 
Type of Sponsor  Private medical college 
 
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 
SUMAYYATASNEEM PARAPUR  Luqman Unani Medical College Hospital and Research Center  Department of OPD Moalijat, Ground floor, Moalajat OPD No. 1, LUMC, 12 Navbag, Bijapur, 586101
Bijapur
KARNATAKA 
7019622214

drsumaiyyatasneem@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee Luqman Unani Medical College Hospital & Research Centre  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: B354||Tinea corporis,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Halela Zard and Sirka  Halela Zard will be procured from the registered herbalist and will be subjected to taxonomical identification by certified botanist. Then, the ingredient will be rendered into a fine powder and mixed in required amount of vinegar as vehicle and will be instructed to the patients for local application on the lesions twice a day for 10 minutes for 21 days. 
Comparator Agent  Terbinafine 1% cream  it will be given for local application in sufficient quantity twice daily for 21 days 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  Clinically as well as KOH diagnosed cases of Tinea corporis without nail and scalp involvement with Body Surface Area less than or equal to 20% 
 
ExclusionCriteria 
Details  Pregnancy and lactation
Patient already on topical and/or systemic antifungal treatment (1 week of topical therapy and/or 4 weeks of systemic antifungal therapy before baseline visit)
Diabetes mellitus
Patients with immunosuppressive disease/drugs
Super-imposed cases of tinea corporis
Non-compliance to the trial protocol
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   An Open list of random numbers 
Blinding/Masking   Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
KOH examination  At baseline and After completion of therapy 
 
Secondary Outcome  
Outcome  TimePoints 
Change in pruritus measured by VAS  At baseline, 10th, 20th, 30th, and 40th day 
Patients global assessment  Baseline and after trial 
Physicians global assessment  Baseline and after trial 
Dermatology Life quality index  Baseline and after trial 
 
Target Sample Size   Total Sample Size="40"
Sample Size from India="40" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   12/01/2021 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   Nil 
Individual Participant Data (IPD) Sharing Statement

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

Response - YES
  1. What data in particular will be shared?
    Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

  2. What additional supporting information will be shared?
    Response - Clinical Study Report

  3. Who will be able to view these files?
    Response - Researchers who provide a methodologically sound proposal.

  4. For what types of analyses will this data be available?
    Response - To achieve aims in the approved proposal.

  5. By what mechanism will data be made available?
    Response - Proposals should be directed to [drsumaiyyatasneem@gmail.com].

  6. For how long will this data be available start date provided 01-05-2022 and end date provided 01-05-2027?
    Response - Beginning 3 months and ending 5 years following article publication.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - NIL
Brief Summary  

Need for The Study:

Dermatophytosis, also referred to as “tinea” is a very common clinical problem caused by superficial mycoses that infect skin, hair, and nails[1][2]. According to WHO, the reported worldwide prevalence is about 20% to 25% [3][4], whereas approximately 30 to 70% adults suffer from asymptomatic superficial mycosis. The incidence of this disease increases with the passage of age [3]. It is clinically manifested by well demarcated, annular, pruritic, and scaly lesions with central clearing [1][5]. Dermatophytes are a larger group of over 51 species divided into six major genera i.e. Trichophyton, Microsporum, Epidermophyton, Nannizzia, Lophophyton, and Arthroderma [6]. Clinically, it is categorized by the name of body parts affected i.e. tinea capitis (head); tinea corporis (body); tinea cruris (groin); tinea unguium (nail), and tinea pedis (feet) [1][5].

Among these subtypes, tinea corporis is the commonest type characterized by dermatophytosis of glaborous skin except palms, soles, and groin area [4][7]. It is treated by both topical and oral antifungal agents in conventional medicine [1][4][5][7]. Systemic antifungals include terbinafine; grisofluvin; itraconazole, and fluconazole[1][4][5][7], but failure reports of systemic therapy and resistance is the most alarming concern; especially mutation in the sequalene peroxidise enzyme that leads to the drug resistance[8]. High recurrence rate was also reported if these therapies are discontinued [9]. Thus, it creates some potential space for further exploration of alternative treatment modality, and Unani medicine may play an important role in its management.

In Unani system of medicine, QÅ«bā is clinically synonymous with Tinea [10] [11]. Moreover, QÅ«bā has been extensively described in various classical text books with special focus on its classification, pathology, prevention, and treatment [12]. QÅ«bā is defined as annular, dry, and pruritic eruptions [11] caused by amalgamation of Mirra Sawda’ (bilious melanchole) into blood or Ruá¹­Å«bat-i Ghalīẓ and Balgham-i Shor (saline phlegm) [10] which is diverted towards the skin by Quwwat-i Ṭabī’yya (natural faculty)  resulting in pruritic skin lesion [13].

The line of treatment of Qūbā is based on Teḥlīl (resolvent) and Talṭīf-i Mawād (demulcent)[12]; and there are many single and compound drugs mentioned in Unani classical literature such as Marham-i Dād [14], Ḥabb-i Qūbā [15], Ushaq (Dorema ammoniacum) with vinegar [13]; Samagh-i ‘Arabi (Acacia gummi) with Sirka [12], Saresham Māhi (Gelatinum/Isinglass) and Kundar (Boswalia serrate) mixed with vinegar [13] for topical application.

Among these, Halela Zard (Terminalia chebula Retz.) mixed with Sirka (vinegar) is recommended for the treatment of Qūbā [11][13]which possesses Teḥlīl and Talṭīf properties. After the extensive online and hand search of literature sources on Qūbā, it’s found that no trial was conducted to validate the safety and efficacy of this drug in the patients of Qūbā.

Keeping all facts in consideration, the present study has been designed to conduct on Qūbā with topical use of Halela Zard and Sirka, entitled “Therapeutic Evaluation of Topical Halela Zard in Treatment of Qūbā (Tinea Corporis) - A Randomised Standard Controlled Trial”.

 

Review of Literature:

 

Dermatophytosis, publicly called as ringworm[3][4], is a fungal infection of skin that have global significance. It is highly prevalent in tropical and subtropical regions of the world [7]. Tinea is a Latin word implying the worm of serpentine nature for skin lesion [3]. Dermatophytes are inoculated into the host skin through penetration followed by full-blown lesions mediated by proteases, serine-substilisins, and fungolysin which cause digestion of keratin network into oligopeptide or amino acid and act as potent immunogenic stimuli[16].

Tinea corporis is a superficial dermatophytic infection of skin other than those involving scalp, beard, hands, feet, and groin[4][7]. It is characterized by one or more circular, sharply circumscribed, and slightly erythematous dry scaly, usually hypopigmented patches [17]. In Unani literature, Qūbā is defined as roughness or scaly skin which is black or red in colour. The primary cause of Qūbā is Mirra-Sawda’ (bilious melanchole) produced by excess intake of black bile producing foods [10]. Moreover, Qūbā may be Damawī (sanguineous) due to putrefied blood and morbid fluid mixing in the blood; Raṭūbī due to excess heat and infection and Sawdāwī due to burnt humours or excessive black bile. The sanguineous lesion appears reddish, while Raṭūbī lesion is whitish to reddish and yellowish in colour. However, the lesion of Sawdāwī Qūbā appears deep brown in color [18].

According to Ibn Sīnā, Qūbā may be of certain types, such as Qūbā Damawī (sanguineous) marked by oozing of fluid from the annular lesions; it may also be caused by saline phlegm mixed with abnormal black bile resulting in dry lesions. Few other types are Qūba Sā‘ī (creeping ring worm), Khabīth (malignant/morbid), and putrefied one[12].

Ismāīl Jurjānī said that Qūbā is caused by pruritic Khilṭ-i Fāsid (morbid humour) or Khilt-i Ghaliz (thick humour) and Sawdāwī (black bilious) blood. The other potential cause is diversion of morbid matter from internal to external part of the body resulting in Qūbā under the influence of Quwwat-i Tabī’yya [13]. It is treated on the principle of Tanqiya (elimination of morbid material from the body), Teḥlīl (resolution) and Talṭīf-i Mawād (attenuation) [12]. Hence, drugs which eliminate Sawda’ out of the body are employed in its treatment besides resolvent and dessicant drugs. A number of single and compound drugs have been prescribed by Unani scholars in treatment of Qūbā. Moreover, various regimenal procedures such as Ta‘līq al-‘Alaq (leeching) [12]; Ḥammām (therapeutic bath) [12][13]; Hijāma bi’l Sharṭ (wet cupping) [13], and Faṣd (venesection) are also prescribed [10][12]. Among these single drugs, Halela Zard is a potent antifungal plant based single drug and it possesses Mushil-i Ṣafra’ (cholagogue), Qābiḍ (astringent), and Muqawwi-i Mi’da (stomachic) actions as mentioned in Unani classical literature [19][20]. The renowned Unani scholar Ahmad al-Hasan al-Jurjāni has written in his voluminous book “Dhakhīra Khwārizm Shāhi” that Halela Zard (Terminalia chebula) should be mixed with Sirka (vinegar) and applied topically on the dermatophytic lesion[13].

Halela Zard (Terminalia chebula, Retz.) belongs to the family of Combretaceae. Its habitat is throughout India, especially West Bengal; Tamil Nadu; West Coast, and Western Ghats. Its fruit is used for thee therapeutic purpose, and the chief chemical constituents are chebulin; palmitic acid, and behenic acid.  The reported pharmacological actions are anti-inflammatory; carminative; digestive; laxative; purgative; antiseptic with indications in wound; ulcers; inflammation; skin diseases; neuropathy, and general debility [21]. Dutta B K and Rubini B , et al reported that the aqueous extract of Terminalia chebula fruit has potent anti-fungal activity, especially against Trichophyton rubrum [22] [23]. Sirka is an acidic agent which helps in reduction of growth of the fungus [16].

Thus, it is hypothesized that Halela Zard along with Sirka as a vehicle will be very effective in amelioration of tinea corporis as the reported antifungal action and its use in treatment of Qūbā by Unani scholars. The control drug “Terbinafine” is a standard drug for treatment of tinea with significant antifungal action [24][25][26].

 

Keeping the above concepts and claim in view, the present study entitled “Therapeutic Evaluation of Topical Halela Zard in Treatment of Qūbā (Tinea Corporis) - A Randomised Standard Controlled Trial” has been designed for the treatment of T. corporis.

List of References:

 

1.        Kim B Y, Thomas J L. Approach to the Patient with a Skin Disorder. In: Jameson JL, Kasper DL, Longo DL, Fauci AS, Hauser SL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine, volume-1. 20th ed. NEW YORK: Mc-Grill Education; 2018. p. 335–6.

2.        HENRY W. LIM. Goldman-Cecil Medicine. In: LEE G, ANDREW S, editors. Goldman-Cecil Medicine. 25th ed. NEW YORK: Elsevier; 2016. p. 2670.

3.        Carol A K. Mucormycosis. In: Jameson JL, Dennis L. Kasper, Longo DL, Fauci AS, Hauser SL, Loscalzo J, editors. Harrison’s Principles of Internal Medicine, volume-1. 20th ed. NEW YORK: Mc-Grill Education; 2018. p. 1546.

4.        Lauren N C, Stefan M S. Fungal Diseases. In: Kang S, Amagai M, Bruckner AL, H. AE, Margolis DJ, McMichael AJ, et al., editors. Fitzpatrick’s Dermatology Volume-I. 9th ed. NEW YORK: McGraw Hill Education; 2019. p. 2926 to 2944.

5.        Neena K. Illustrated Synopsis of Dermatology and Sexually Transmitted Diseases. 4th ed. Delhi: Elsevier; 2011. 282–290 p.

6.        de Hoog GS, Dukik K, Monod M, Packeu A, Stubbe D, Hendrickx M, et al. Toward a novel multilocus phylogenetic taxonomy for the dermatophytes. Mycopathologia. 2017;182(1–2):5–31.

7.        Hay RJ, Ashbee HR. INFECTIONS ANDINFESTATION. In: Griffiths C, Barker J, Bleiker T, Robert C, Creamer & D, editors. ROOK’S TEXTBOOK OF DERMATOLOGY volume-1. 9TH ed. United Kingdom: Blackwell, Wiley; 2016. p. 32.35-32.37.

8.        Shenoy M, Jayaraman J. Epidemic of difficult-to-treat tinea in India: Current scenario, culprits, and curbing strategies. Arch Med Heal Sci. 2019;7(1):112.

9.        Varma S MR. The Great Indian Epidemic of Dematophytosis: An Appraisal. Indian J Dermatol. 62(3):227-.

10.      Abu al-Hasan Ali Ibni Abbas Mutib Majusi. KAMILUS SANA. New Dehli: Idara kitab Al-shifa; 2010. 432 p.

11.      Hakim Muhammed Akbar Arzani. MEZANI ALTIB. NEW DELHI: Idara kitab Al-shifa; 2002. 249 p.

12.      Sina SABAI. ALQANUN. 2nd ed. New Dehli: Idara kitab Al-shifa; 2014. 1431–1432 p.

13.      Ahmad al-hasan al-jurjani. DHAKHIRA KHWARZAM SHAHI. New Dehli: Idara kitab Al-shifa; 2010. 24–26 p.

14.      Hakeem Abd Alrahim Jaleel. MUJARRABATI LUQMANI. Devband: A’jaz Publishing House; 116–119 p.

15.      Hakeem Muhammad Kabir Aldeen. BAYAZI KABIR. New Dehli: Central Council for Reasearch in Unani Medicine; 2008. 214 p.

16.      Sahoo AK, Mahajan R. Management of tinea corporis, tinea cruris, and tinea pedis: A comprehensive review. Indian Dermatol Online J. 2016;7(2):77.

17.      Neuhaus WJTBDEI. Andrews’ Diseases of the Skin. 12th Editi. Elsevier; 285–290 p.

18.      M AAA bin MT. AlMUALAJATH ALBUQRATIYA Volume-2. New Dehli: Central Council for Reasearch in Unani Medicine; 1997. 211–213 p.

19.      Hakeem Kabiruddin. MUKHZAN ALMUFRADAT. New Dehli: A’jaz Publishing House; 590–591 p.

20.      IBN B. ALJAMA ALMUFARADAT ALADVIA WA ALAGHZIA VOL-4. New Dehli: Central Council for Reasearch in Unani Medicine; 2003.

21.      Narayan DP, S.S P, Arun KV, Tarun K. A HANDBOOK OF MEDICINAL PLANTS A COMPLETE SOURCE BOOK. Jodhpur: Agrobios (India); 2013. 508 p.

22.      Dutta BK, Rahman I, Das T. Antifungal activity of Indian plant extracts Antimyzetische Aktivität indischer Pflanzenextrakte. Mycoses. 1998;41(11/12):535–6.

23.      Rubini B, Shanthi G, Rajarajan. S, Soundhari. C. Antifungal activity of Terminalia chebula and Terminalia catappa on two dermatophytes. J Med Aromat Plants. 2013;4(2):15-19:15–9.

24.      Choudhary S V, Bisati S, Singh AL, Koley S. Efficacy and safety of terbinafine hydrochloride 1% cream vs. sertaconazole nitrate 2% cream in tinea corporis and tinea cruris: a comparative therapeutic trial. Indian J Dermatol. 2013;58(6):457.

25.      Nepal A. Efficacy of topical terbinafine and clotrimazole in the treatment of dermatophytoses: a Clinical and Microbiological Comparision. Med J Pokhara Acad Heal Sci. 2018;1(1):31–4.

26.      Dattatreyo C, Sudip KG, Sukanta S, Saswati S, Avijit H, Radharaman D. Efficacy and tolerability of topical sertaconazole versus topical terbinafine in localized dermatophytosis:A randomised observer-blind,parallel group study. indian J Pharmacol. 2016;659–64.

27.      Das A, Sil A, Sarkar TK, Sen A, Chakravorty S, Sengupta M, et al. A randomized, double-blind trial of amorolfine 0.25% cream and sertaconazole 2% cream in limited dermatophytosis. Indian J Dermatology, Venereol Leprol. 2019;85(3):276.

 
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