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Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Warts

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Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

All Drugs and Chemicals

Immunomodulating Agents

Intralesional injection of 0.3ml candida antigen into largest wart at baseline visit and then every 3 weeks +/- 3 days for a maximum of 10 treatments.

Candida Antigen

Mayumi Nakagawa, MD, PhD

The purpose of this study is to look at how people respond to the treatment of warts through use of the Candida antigen to get an immune response to rid the body of human papillomavirus (HPV). The immune system is the part of the body that fights infections like HPV which causes warts. This research study will examine the response of your wart when injected with a portion of a common yeast (candida) which is the study drug. Your immune system response will also be looked at by doing a test called an ELISPOT assay. This test is done on blood samples. The results of this test may help us to determine how the Candida antigen affects your wart.

The use of recall antigens for treating warts is not yet Food and Drug Administration (FDA) approved. The primary goal of this work was to assess the safety of Candin as an investigational new drug (IND) for the treatment of warts. In addition, clinical resolution of treated and untreated warts was evaluated and immunologic responses were examined using an ex vivo interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay in order to elucidate the immunologic mechanisms behind the successful regression of warts in patients undergoing Candin injection immunotherapy.

Study With Candida Antigen for Treatment of Warts

A Phase 1 Study to Evaluate the Immunologic Mechanisms Underlying Wart Resolution After Intralesional Immunotherapy With Candida Antigen

Immunologic responses from peripheral blood mononuclear cells collected prior to vaccination and post-vaccination were measured by ex vivo interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay to human papillomavirus type 57 L1-peptide.

When the participant completed the protocol, clinical resolution of the injected wart was determined by the overall percentage of resolution from the initial visit. Participants were classified as 'complete responders' if they had complete resolution of the injected wart, 'partial responders' if the injected wart regressed between 25% and 99%, and 'non-responders' if they had not achieved at least 25% regression of the injected wart.

When the participant completed the protocol, clinical resolution of 1st anatomically distant, non-injected wart was determined by the overall percentage of resolution from the initial visit.

When the participant completed the protocol, clinical resolution of 2nd anatomically distant, non-injected wart was determined by the overall percentage of resolution from the initial visit.

Allermed Laboratories, Inc.

University of Arkansas

Mayumi Nakagawa

All patients enrolled into the study were treated with intralesional injection of 0.3ml candida antigen into largest wart at baseline visit and then every 3 weeks +/- 3 days for a maximum of 10 treatments.

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Complete responder

Partial responder

Non-responder

The participants were analyzed if they completed the protocol by achieving complete resolution of the treated wart, receiving the maximum of 10 treatments, or by having less than 25% resolution of the treated wart after 5 treatments.

Number of Participants With Clinical Resolution of Injected Wart

Complete resolution of 1st non-injected wart

Partial resolution of 1st non-injected wart

Participants with 1st anatomically distant, non-injected wart were analyzed.

Number of Participants With Clinical Resolution of 1st Anatomically Distant, Non-injected Wart

The participants with 2nd anatomically distant, non-injected wart were analyzed.

Number of Participants With Clinical Resolution of 2nd Anatomically Distant, Non-injected Wart

The interferon-γ enzyme-linked immunospot assay was performed on available samples from participants who completed the study.

Number of Participants With Immune Response to Human Papillomavirus Type 57 (HPV-57) L1-peptide

Overall Study

Immune System Diseases

Neoplasms

Mouth and Tooth Diseases

Rare Diseases

Hypersensitivity

Leukoplakia

Leukoplakia, Oral

Precancerous Conditions

Pathological Conditions, Anatomical

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Leukoplakia

Oral Cancer

Anti-Infective Agents

Central Nervous System Depressants

Clotrimazole

Miconazole

Fluconazole

Ethanol

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormones

Hormone Antagonists

uniform, flat, thin, smooth/ wrinkled/corrugated surface throughout the white lesion.

Tab Fluconazole 100 mg as a mouthwash ( tablet dissolved in 10 ml of drinking water and used as a mouth rinse for 2 minute and swallowed) once a day for 14 days

mixture of red and white lesions with a irregularly speckled/ nodular/ verrucous surface Tab Fluconazole 100 mg as a mouthwash ( tablet dissolved in 10 ml of drinking water and used as a mouth rinse for 2 minute and swallowed) once a day for 14 days

30 healthy controls ( age and sex matched) would also be recruited from patients who are reporting for other routine dental problems.

( Tab Fluconazole 100 mg as a mouthwash ( tablet dissolved in 10 ml of drinking water and used as a rinse for 2 minute and swallowed) once a day for 14 days WHO criteria 5As and 5Rs for tobacco cessation

Shalini Gupta, MDS,FDSRCS

This study aims to determine the correlation between candida and pro- inflammatory cytokines response in Oral Leukoplakia(OL) with antifungal therapy. Ethical clearance from the Institutes ethical committee and Informed written consent from the patient will be obtained. The study group would comprise of clinically and histopathologically confirmed cases of OL (60 patients). The control group would be 30 dental patients ( age \& sex matched) who do not any malignancy, OL or any other potentially malignant disorder of oral mucosa. Patients who have any predisposing factor for oral candidiasis will be excluded from the study. Swabs will be taken from the oral lesion and cultured for candida to determine phenotypes, virulence attributes and antifungal sensitivity. Sterile PVA opthalmic sponges will be used to collect sample from the surface of oral epithelium and then processed to determine levels of pro- inflammatory cytokines (IL-6, IL-8. IL-17, TNFα). This procedure will be repeated in study group 2 weeks after a course of antifungal therapy. The results will be tested statistically at a confidence level of 95%.

Objectives

1. To determine the association of candida phenotypes, virulence attributes ( Secreted aspartyl proteinases, biofilm formation, Phospholipase) and antifungal sensitivity with clinicopathologic characteristics in oral leukoplakia
2. To determine the secretion and levels of pro-inflammatory cytokines ( IL-6, IL-8. IL-17, TNFα ) in oral leukoplakia before and after antifungal therapy.
3. To study the correlation between candida and pro-inflammatory cytokines in oral leukoplakia with antifungal therapy

Detailed methodology including study design, outcome measures, sample size and statistical analysis.

Study design:

Prospective case- control observational study

Selection of patients:

The patients in the study group and control group will be consecutively recruited from the Oral Medicine \& Radiology clinic at Centre for Dental Education \& Research AIIMS.

Sample size:

The study will include 60 OL ( 30 Homogenous OL, 30 Non- Homogenous OL) and 30 healthy controls

Clinicopathologic characteristics:

The clinical characteristics and staging/grading would be recorded as per prepared proforma for each group. Written informed consent would be taken before any further investigation. History of tobacco, betel nut, alcohol habits with frequency, duration of habit and current status, oral burning sensation with Visual Analogue Scale (VAS) scores will be Routine blood investigations would be done before incisional biopsy and histopathological confirmation of the diagnosis. The H \& E histopathological features with Periodic Acid Schiff (PAS) staining would be recorded and grading done for study group as per standard World Health Organization criteria. The clinical staging of OL will be done as per OL staging system (OLEP) ( van der Waal 2000) with photographic records of lesions by two calibrated observers.Tobacco,betel nut and alcohol cessation counselling and oral hygiene instructions will be given.

Sample collection for study:

A). Candida phenotypes, virulence and antifungal sensitivity study. Collection , transport and processing: Two oral swabs from each patient ( pre-wet with sterile normal saline) will be taken from the oral lesion and sent to the Mycology Laboratory, Department of Microbiology for further processing as per standard laboratory procedures.

Direct microscopy: One swab sample will be examined by microscopy for detection of yeast cells by preparing gram stain.

Culture: The second swab will be inoculated on Sabouraud dextrose agar (SDA) medium with gentamicin and will be kept at 37°C for incubation for 48 hours. Gram staining will be performed on any growth morphologically resembling to that of yeast.

Phenotypic identification: Identification of isolates was performed by using germ tube, morphology on corn meal agar, colour on triphenyl tetrazolium chloride and CHROM agar medium Determination of virulence factors of Candida spp Various virulence factors like phospholipase activity, Secreted aspartyl proteinase (SAP) and Biofilm formation (BF) will be determined as per the standard protocol.

Determination of Phospholipase (PL) activity Phospholipase activity will be measure by growing cells on egg yolk agar medium and measuring the size of the zone of precipitation. A cell suspension of 106 yeast cells/ml in saline will be prepare and 5μl will be place on the surface of the egg yolk medium. The culture will then incubated at 37°C for 7-8 days, after which the diameter of the precipitation zone around the colony will be determine. Phospholipase activity (Pz) will be measure by dividing colony diameter by the diameter of the precipitation zone (pz) around the colony formed on the plate. Each isolate will be tested in duplicate. The C. albicans SC 5314 strain will be used as positive control.

Determination of Secreted aspartyl proteinase (SAP) activity All isolates will be tested for their ability to grow and produce a clear zone of hydrolysis in bovine serum albumin (BSA) agar. . A 5μl of 1x106 cells /ml will be placed on solid medium and will be incubated at 37°C for 3-4 days. Subsequently, clearing of the opacity by hydrolysis of precipitated albumin will be recorded. The C. albicans SC 5314 strain will be used as positive control.

Determination of Biofilm formation (BF) A 100μl volume of 1 x 106 cells /ml suspension will be place on sterile, polystyrene, flat-bottom 96-well microtitre plates and will be incubated for 48 h at 37°C for adherence and biofilm. After 48 hr wells will be washed with PBS and a semi-qualitative measure of biofilm will be detected by XTT \[2,3-bis (2-methoxy-4nitro-5-sulfo-phenyl) - 2H - tetra-zolium-5-carboxanilide\] -reduction assay A colorimetric change in the XTT-reduction assay, a direct correlation of the metabolic activity of the biofilm, will then be measure in a microtiter plate reader at 490 nm after 2 hr of incubation.

Antifungal susceptibility testing of isolates Antifungal susceptibility for voriconazole fluconazole and clotrimazole will be performed by disk diffusion method as per the CLSI M44-A2 recommendation on the yeast isolates.

B). Pro- Inflammatory cytokines study Sample collection of oral secretions from lesion Four Sterile PVA ophthalmic sponges (Merocel) will be used to collect samples of oral secretions for four pro-inflammatory cytokine study from the oral lesion (other than biopsy site). This is a non- invasive method and makes it site -specific which is an advantage over other serum and saliva estimations. In addition, assessment of local cytokine levels via longitudinal sampling in patients undergoing antifungal therapy in OL may allow for an understanding of the temporal nature of cytokine elevation and clinical response to antifungals.

This procedure will be done for both the study group and control group. The subjects will be asked to abstain from eating, drinking and rinsing the mouth at least 2 hours prior to sampling. The sponges will be pre-wet with sterile normal saline, kept in contact with the lesion without rubbing or movement or 1 minute and then immediately stored in sterile containers at -80 °C till further analysis in Biochemistry department AIIMS. A photographic and clinical record of the sample site will be kept with the patient proforma for future reference. This procedure will be repeated at the same site after antifungal therapy for study group and a photographic record will be kept for comparison. Ethical clearance from Institute ethics board will be taken. Informed written consent will be obtained and information regarding the study would be given to the study subjects and controls prior sample collection.

Estimation of IL-6, IL-8, IL-17 and TNFα levels by ELISA The opthalmic sponges (Merocel ) will be thawed at room temperature for 10 min. Sponges will then be inserted into a microcentrifuge tube containing a 0.2 μm filter (SpinX centrifuge tube), equilibrated by adding 300 μl of extraction buffer and incubated for 30 min at 4 °C, followed by centrifugation at 4 °C for 30 min at 14,000 rpm. After centrifugation, the resultant supernatant will be collected for the estimation of IL-6, IL-8, IL-17 and TNFα levels by ELISA method with commercially available kits. The supernatant will be stored at -80 °C until use.

A monoclonal antibody against the antigens (IL-6, IL-8, IL-17 and TNFα) has been pre-coated onto the wells of the microtiter strips provided. Antigens present in the sample or standard will be incubated with the plates to allow binding of antigens to the antibody. This is followed by the addition of a primary monoclonal anti- IL-6, IL-8, IL-17 and TNFα antibody respectively conjugated to biotin in respective microtiter plates. An avidin-HRP conjugated antibody specific for primary antibody will then be added to the wells. After incubation and following a wash, to remove any unbound antibody enzyme reagent, a TMB one-step substrate reagent reactive with HRP will be added to the wells. The color development will be terminated by adding acid and absorbance was measured at 450 nm. A reference curve will be obtained by plotting the different concentrations of standard samples versus absorbance and levels of the antigens in samples tested will be calculated by its standard plot.

Antifungal therapy The study group will be treated with antifungal therapy ( Tab Fluconazole 100 mg as a mouthwash ( tablet dissolved in 10 ml of drinking water and used as a rinse for 2 minute and swallowed) once a day for 14 days). The procedure will be demonstrated to each study subject before starting the treatment. The oral burning sensation and clinical characteristics of the lesions with intraoral photographs will be recorded after antifungal therapy.

Statistical analysis:

The distribution of candida phenotypes, virulence attributes and antifungal sensitivity in the study and control groups would be correlated with levels of IL-6, IL-8, IL-17 and TNFα and clinicopathological characteristics. Correlations between virulence factors and clinical characteristics will be determined. Cohens kappa statistic will be used to determine intraobserver reliability. A comparison of the levels of pro inflammatory cytokines(IL-6, IL-8, IL-17 and TNFα) before and after antifungal therapy will be done in the study group. The results would be tested for statistical significance.The Chi- square and the Mann- Whitney U tests will be used to estimate the statistical significance of difference observed between the groups.

7.Ethical Clearance Obtained

Candida Associated Cytokines in Oral Leukoplakia

Association of Candida and Antifungal Therapy With Pro-inflammatory Cytokines in Oral Leukoplakia- A Pilot Study

maximum Length( L) and width (W) L1: L/W ≤ 2 cm L2: L /W 2-4 cm L3: L/W ≥ 4cm

il6,il8,il17,TNF-alpha by ELISA before and after antifungal treatment

Scores as \[ 0- no change, 1- minimal change ( Reduction in erythema \< 1cm of oral lesion, and 2- significant change( Reduction in erythema ≥ 1cm of oral lesion)

Scores as \[ 0- no change, 1- minimal change ( Reduction in thickness \< 1cm of oral lesion, and 2- significant change( Reduction in thickness ≥ 1cm of oral lesion)

Swabs for smear or culture positive for Candida

Phospholipase activity (Pz) was measured by dividing colony diameter by the diameter of the precipitation zone (Pz) around the colony formed on the plate. A Precipitation zone (in mm) around colony 1.0 : 0 negative (-), 0.99-0.9 : 1 weak (+), 0.89-0.8: 2 poor (++), 0.79-0.7: 3 moderate (+++), \< 0.69: 4 Strong positive(++++),

Secreted aspartyl proteinase activity was measured by dividing colony diameter by the diameter of the precipitation zone (Pz) around the colony formed on the plate. A Precipitation zone (in mm) around colony 1.0 : 0 negative (-), 0.99-0.9 : 1 weak (+), 0.89-0.8: 2 poor (++), 0.79-0.7: 3 moderate (+++), \< 0.69: 4 Strong positive(++++),

Absorbance values of test wells at 490nm of XTT reduction assay- absorbance values of control

Using CLSI document M44-A for disk diffusion method for Fluconazole (25 μg), Voriconazole (1 μg) and Clotrimazole (50 μg) S: Sensitive R: Resistant I: Intermediate

Mild Dysplasia Moderate Dysplasia Severe Dysplasia PAS stain positive/ negative

Histological features of Oral Squamous Cell Carcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study With Candida Antigen for Treatment of Warts	NCT00569231	Warts HPV	Candida Antigen	18 Years - 50 Years	University of Arkansas
Candida Associated Cytokines in Oral Leukoplakia	NCT04712929	Oral Leukoplaki...	Fluconazole	18 Years - 100 Years	All India Institute of Medical Sciences, New Delhi
Candida Associated Cytokines in Oral Leukoplakia	NCT04712929	Oral Leukoplaki...	Fluconazole	18 Years - 100 Years	All India Institute of Medical Sciences, New Delhi
Candida Associated Cytokines in Oral Leukoplakia	NCT04712929	Oral Leukoplaki...	Fluconazole	18 Years - 100 Years	All India Institute of Medical Sciences, New Delhi

Spots Global Cancer Trial Database for candida

Every month we try and update this database with for candida cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for candida

Every month we try and update this database with for candida cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for candida cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.