Brief resume of the intended work:                                                

Need of the study:

Urinary problems are the frequently encountered issues in women and are capable of affecting all aspects of their life. The International Continence Society (ICS) defines Stress Urinary Incontinence (SUI) as, “the complaint of any involuntary loss of urine on effort or physical exertion or on sneezing or coughing”.¹

Worldwide, SUI is predominant in females and the mean prevalence in the various studies is 25%.² It can, however, range from 25% in young women to 45% among the elderly.³ Because there is not a standard established definition of SUI for epidemiologic research, the reported variation in prevalence rates reflects differences in populations studied, as well as differences in the definition of SUI used by the investigators.⁴

It is a hidden factor that significantly hampers the quality of life and is ‘under reported’ and ‘under treated’ due to traditional and modest lifestyle.^5,6 NICE guidelines recommend the use of duloxetine (SSNRI) as a second line of treatment which has plenty of side effects including somnolence, dysgeusia, hypoesthesia, lethargy, paresthesia, psychomotor agitation, tremor, vertigo and suicidal attempts.^7,8 Failure of pharmacological intervention may result in a need for surgery. These complications warrant for a simple, low-cost, low-risk, non-invasive management that can improve the quality of life without prolonging hospital stay or causing undue strain on the patient.

Unani system of medicine with its wealth of knowledge can contribute in this regard. Classical literature recommends the use of ItrÄ«fal-i-SaghÄ«r  ,ItrÄ«fal-i-KabÄ«r, Ayārij-e-Jālinōōs, Kundur and Rōghan-i-Hinā, ShōōnÄ“Ä“z and Sudāāb, AnjÄ“Ä“r and Rōghan-i-Zaitōōn, Arad-i-Juft Balōōt, Tukhm-i-khurfah etc.in the management of SUI.⁹ ItrÄ«fal-i-SaghÄ«r with its constituents of HalÄ“la, BalÄ“la and Ä€mla possesses astringent, antioxidant, nephroprotective and immunomodulator properties. It has been reported to be effective in Salas al-Bawl but has not been validated for the same.¹⁰ Hence this study is designed to evaluate the effectiveness of ItrÄ«fal-i-SaghÄ«r in SUI.

Review of literature:

SUI could be due to many reasons like weakness of the bladder due to Sū’-i- Mizaj al Barid (coldness of temperament), paresis of the bladder and excessive rutÅ«bāt.¹⁰ Which implies that SUI is basically a BalghamÄ« Mard that presents as laxity or abnormal relaxation of the muscles of external sphincter and the pelvic floor. This diagnosis is further confirmed by examining the urine. If there is no burning micturition, the urine appears white in color and the patient doesn’t experience thirst, then it further confirms the diagnosis of Sū’-i- Mizaj al Barid.^9,11

Classical literature also describes a hār type of Sū’-i- Mizaj, that could lead to dribbling of urine. This kaifiyat creates tÄ“z (irritant) urine which the tab‘īyat would want to evacuate as soon as possible leading to incontinence.⁹ However this description is more at par with Urinary Tract Infection (UTI) than with SUI.

The Medical Epidemiologic and Social aspects of Aging (MESA) questionnaire is an authenticated and reliable tool to diagnose the presence of SUI in women.¹² The MESA questionnaire is consists of 2 separate parts, with 6 questions concerning urgency urinary incontinence and 9 concerning stress urinary incontinence. Its reliability allows it to be used both as a diagnostic tool and outcome assessment. Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) are well known broadly used condition- specific questionnaires which give an idea on the quality of life.¹³

According to NICE guidelines first line of management should be done through lifestyle modifications like weight reduction, maintaining a bladder diary, decreasing fluid and caffeine intake.^7,14It also recommends offering a trial of supervised pelvic floor muscle training of at least 3 months duration to women with stress or mixed urinary incontinence. On extreme need Dulexotine (SSNRI) can be prescribed with precaution. On the failure of all the above regimens surgical intervention is recommended.⁷

Classical literature recommends the use of Itrīfal-i-Saghīr, for the management of SUI as it possess anti-inflammatory, analgesic, purifying, healing, astringent, nephroprotective and immunomodulator activities.

Objectives of study:

●      To evaluate the effect of ItrÄ«fal-i-SaghÄ«r in Stress Urinary Incontinence

MATERIAL METHODS

Source of data:

Patients attending the female OPD and IPD, Department of IlmulQabalatwaAmraz-e-Niswan, NIUM, Bangalore.

Study design: Single blind, randomized, placebo controlled study.

Sample size: 60 patients

Test Group = 30

Control Group = 30

Method of collection of data

●      History taking and clinical examination

●      Investigations

Selection criteria: Clinically assessed patients with Stress Urinary Incontinence will be included in the study after obtaining voluntary consent.

Inclusion criteria:

●      Women 20-60 years of age, with or without genital prolapse (Grade 1 and 2).

●      Women who satisfy the criteria for Stress Urinary Incontinence according to MESA questionnaire.

Exclusion criteria:

·       Uncontrolled HTN, DM and Malignancies

●      Pregnant and lactating women

●      Neurological deficit incontinence (Stroke, spinal injury)

●      UTI or fibroid/cyst >3cm or uterine prolapse (grade 3 and 4)

●      History of medication/surgery for SUI in past three months

Subjective Parameters: Losing urine during Coughing/ sneezing/ lifting/ bending/ walking/ straining (MESA).

Objective Parameters: IIQ-7, UDI-6 questionnaire.

Intervention

Test group: ItrÄ«fal-i-SaghÄ«r.¹⁵

Control group:  Placebo (mixture of wheat flour and honey).

Kegel’s exercise will be advised in both the groups.

Ingredients:

Pōst HalÄ“la Zard         (Terminalia chebula) 20gms

Pōst HalÄ“la KābulÄ«      (Terminalia chebula) 20gms

HalÄ“la Siyāh               (Terminalia chebula) 20gms

Pōst BalÄ“la                 (Terminalia bellerica)  20gms

Ä€mla Khushk               (Emblica officinalis) 20gms

Rōghan-i-Zard            (Ghee) QS

Qand-i-SafÄ“d              (Sugar) 300gms

Method of preparation: Itrīfal-i-Saghīr is prepared as per standard preparation.^15,16

Route of administration, dosage, duration:

Test group: 10 gms of ItrÄ«fal-i-SaghÄ«r BD orally for 8 weeks.¹⁵

Control group: Placebo (mixture of wheat flour and honey) BD, orally for 8 weeks.

Duration of protocol therapy: 2 months

Procedure of the study: Diagnosed cases of SUI will be selected and randomly allocated considering the inclusion and exclusion criteria (n=60) and written informed consent will be taken. Pelvic floor assessment will be done according to modified oxford grading system.¹⁷ Test group will be given ItrÄ«fal-i-SaghÄ«r   and control group will be given placebo 10g BD, every day for 2 months. During the study follow up of the patient will be done once a month and one month after trial completion.

Follow up:

·       During trial: Every month for 2 months

·       After trial: One month after trial completion

Duration of study: 1 and half years

Withdrawal criteria:

·       Failure to follow protocol therapy

·       The case in which adverse reaction is noted

Informed consent: Patients fulfilling inclusion criteria will be given an information sheet having the details regarding the nature of the study and the procedure being used. Patients will be given enough time to go through the study details mentioned in the information sheet. They will be given an opportunity to ask questions and if they agree to participate in the study, they will be asked to put in their signature on the form.

Assessment of efficacy: The assessment of efficacy of the test and control drug will be done through change in MESA and IIQ-7, UDI-6 questionnaires.

Primary outcome: Change in MESA questionnaire¹¹

Secondary outcome: Change in IIQ-7, UDI-6¹²

Assessment of safety:

·       Clinical signs and symptoms

·       Laboratory investigations

Adverse drug documentation: Any adverse reaction of the drug will be documented.

Documentation: The report will be submitted to the department after completion of the study.

Statistical analysis: The appropriate tests will be applied to analyze the data. The descriptive statistical analysis will be used in the study. Results on the continuous measurement will be presented in mean (SD) and results on the categorical measurements will be presented in number (%) with 5% level of significance and 95% confidence interval.

Does the study require any investigation or intervention to be conducted on patients or other human animals? Yes

Investigations:

Pre-test: CBC, RBS, CUE, Urine Culture and Sensitivity, USG Pelvis, Pap smear.

Pre and Post-test: ALT, AST, Alkaline phosphatase, Blood Urea, Serum Creatinine.

Has ethical clearance been obtained from your institution in case of 7.3 – Ethical clearance obtained vide IEC No: NIUM/IEC/2020-21/010/ANQ/01

List of references

1. Abrams P, Cardozo L, Fall M, et al; Standardization Sub-Committee of the International Continence Society.  The standardization of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society.  Urology. 2003;61(1):37-49.
2. Hunskaar S, Burgio K, Diokno A, Herzog A, Hjälmås K, Lapitan MC. Epidemiology and natural history of urinary incontinence in women. Urology. 2003;62(4 Suppl 1):16-23.
3. Hunskaar S, Burgio K, Clark A, Lapitan MC, Nelson R, Sillen U, et al. Epidemiology of urinary and faecal incontinence and pelvic organ prolapse (POP). Health Publications Ltd; 2005.
4. Luber KM. The definition, prevalence, and risk factors for stress urinary incontinence. Rev Urol. 2004;6Suppl 3(Suppl 3):S3-S9.
5. Kim JC, Chung BS, Choi JB, Lee JY, Lee KS, Park WH, Choo MS. A safety and quality of life analysis of intravaginal sling plasty in female stress incontinence: a prospective, open label, multicenter, and observational study. IntUrogynecol J 2007;18(11):1331-5.
6. Tsai YC, Liu CH. Urinary incontinence among Taiwanese women: an outpatient study of prevalence, comorbidity, risk factors, and quality of life. IntUrolNephrol 2009; 41(4):795-803.
7. Stress Urinary Incontinence: Assessment and management/Guidance and guidelines/NICE www.nice.org.uk
8. Maund E, Tendal B, Hrobjartsson A, Jorgensen K, Lundh A, Schroll J et al. Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder: comparison of clinical study reports, trial registries, and publications. BMJ. 2014;348(jun04 2):g3510-g3510.
9. Sina I, Al Qanoon fi Tib. Trans:Khan HH. New Delhi. IdaraKitabusShifa. 2010.p1027-30
10. Jurjani AH, ZakheeraKhwarzmShahi. Trans:Khan HH. New Delhi. IdaraKitabusShifa. 2011.p.531-3
11. Shirbeigi L, Niktabe Z, Masoudi N, Tabrrai M, Nejatbakhsh F. Effect of Thermotherapy on Mixed Urinary Incontinence Based on Persian Medicine: A Case Report TradIntegr Med 2017; 2(3): 129-32.
12. Diokno AC, Catipay JRC, Steinert BW. Office assessment of patient outcome of pharmacologic therapy for urge incontinence. IntUrogynecol J 2002;13:334–8
13. Skorupska, K., Grzybowska, M.E., Kubik-Komar, A. et al. Identification of the Urogenital Distress Inventory-6 and the Incontinence Impact Questionnaire-7 cutoff scores in urinary incontinent women. Health Qual Life Outcomes 19, 87 (2021)
14. Nygaard, Ingrid E. MD, MS; Heit, Michael MD, MSPH Stress Urinary Incontinence, Obstetrics & Gynecology: September 2004;104(3):607-20
15. Kabiruddin M, Al-Qarabadeen, 2^nded. New Delhi: CCRUM; 2006.p11

   16. Anonymous, National Formulary of Unani Medicine, Part 1, 1^sted. New Delhi: Ministry of AYUSH; 2006.p95

    17. Ferreira C, Barbosa P, Souza F, Antônio F, Franco M, Bø K. Inter-rater reliability study of the modified Oxford Grading Scale and the Peritron manometer. Physiotherapy. 2011;97(2):132-138.