Use of Maqui Berry Extract in Treating Oral Candidiasis in Diabetes Mellitus Patients and Systemically Healthy Persons

Study Overview
=================
Brief Summary
-----------------
Fungi from the genus Candida present the saprophytic flora of the cavity. This saprophytic yeast can cause different form of oral infections at immunocompromised patients as well as at subjects with impaired local oral microbiota e.g. wearers of dentures. The most common cause of oral candidiasis is Candida albicans, but recently, non-albicans species has also been commonly isolated. One of the reasons for growing frequency of non-albicans species is traditional antifungal therapy. Standard antifungal therapy, which means elimination of yeasts, lead to antimicrobial resistance, dysbiosis and higher incidence of non-albicans species In order to overcome these limitations, the new antimicrobial therapy is based on anti-virulence strategy. This approach relays on disarming the microorganism, instead of killing or stopping their growth, which is especially important for saprophytes. In case of Candida albicans the main goal is preventing transition from cell to hyphal form.

Detailed Description
-----------------
The aim of this study is to assess the efficiency of a dietary supplement based on Maqui Berry extract (CandBerrol® lozenge, Phytonet, Serbia) in treatment of oral candidiasis in patients who are treated with standard antifungal therapy - miconazole, 2%, (Daktanol® oral gel, Galenika, Serbia). The study would be conducted at Clinic for Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade. The subjects would be recruited from the pool of patients who come for the treatment of suspected oral candidiasis. A total of 90 patients with confirmed fungal infection (Candida spp.) of the oral cavity would be included in the study and divided into three groups (30 subjects per group), matched by gender and age: Group A: systemically healthy subjects wearing acrylate dentures Group B: subjects with diabetes mellitus without acrylate dentures Group C: subjects with diabetes mellitus wearing acrylate dentures Each group is further subdivided into two treatment subgroups: Active control, treated with miconazole, 2% (Daktanol® oral gel, Galenika, Serbia). Experimental, treated with miconazole, 2% with Maqui Berry extract (CandBerrol® lozenge, Phytonet, Serbia) During the first examination, patients signed their consent to participate in the research based on written and oral information about the type, duration and expected outcome of the research. Following signing the consent, the research sheet specifically designed for this study would be fulfilled. Both therapy protocol (active control and experimental therapy) would be administrated for 14 days. Therapy protocols would also include advices for oral and denture hygiene and diet. Clinical and microbiological controls would be conducted after 7th, 18th and 30th days from the start of therapy. Patients who would not be able to follow the study instructions, would be excluded from the study. Statistical analysis would be analyzed using the SPSS software program using appropriate statistical tests.

Official Title
-----------------
The Effect of Using Preparations With Maqui Berry Extract in Treating Oral Candidiasis in Patients With Diabetes Mellitus and Systemically Healthy Persons

Conditions
-----------------
Oral Candidiases

Intervention / Treatment
-----------------
* Drug: Miconazole
* Dietary Supplement: CandBerrol® lozenges


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age over 18 Candida spp. infection (Clinical signs, symptoms and microbiological confirmation of infection) Systematically healthy wearing acrylate denture (Group A) Diabetic patients with/without acrylate denture (Groups B and C) Exclusion Criteria: Presence of other systemic diseases Presence other oral mucosal contions

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy subjects with acrylate dentures and oral Candida spp infection-Miconazole group<br>These group includes systematically healthy patients wearing acrylate dentures and with microbiologically confirmed oral infection caused with Candida spp. These patients were treated with Miconazole gel. | Drug: Miconazole<br>* Protocol for active control groups includes use of Miconazole Oral gel for 14 days with frequency of four time per day.<br>* Other names: Daktanol®;|
| Experimental: Healthy subjects with acrylate dentures and oral Candida spp infection-Candberrol-Miconazole group<br>These group includes systematically healthy patients wearing acrylate dentures and with microbiologically confirmed oral infection caused with Candida spp. These patients were treated with Miconazole gel and Candberrol lozenges. | Drug: Miconazole<br>* Protocol for active control groups includes use of Miconazole Oral gel for 14 days with frequency of four time per day.<br>* Other names: Daktanol®;Dietary Supplement: CandBerrol® lozenges<br>* Protocol for experimental groups includes use of Miconazole Oral gel and CandBerrol® lozenges for 14 days with frequency of four time per day<br>|
| Active Comparator: Diabetic subjects without dentures and with oral Candida spp infection - Miconazole group<br>These group includes diabetes mellitus patients without acrylate dentures and with microbiologically confirmed oral infection caused with Candida spp. These patients were treated with Miconazole gel. | Drug: Miconazole<br>* Protocol for active control groups includes use of Miconazole Oral gel for 14 days with frequency of four time per day.<br>* Other names: Daktanol®;|
| Experimental: Diabetic subjects without dentures and with oral Candida spp infection - Miconazole-Candberrol group<br>These group includes diabetes mellitus patients without acrylate dentures and with microbiologically confirmed oral infection caused with Candida spp. These patients were treated with Miconazole gel and Candberrol lozenges. | Drug: Miconazole<br>* Protocol for active control groups includes use of Miconazole Oral gel for 14 days with frequency of four time per day.<br>* Other names: Daktanol®;Dietary Supplement: CandBerrol® lozenges<br>* Protocol for experimental groups includes use of Miconazole Oral gel and CandBerrol® lozenges for 14 days with frequency of four time per day<br>|
| Active Comparator: Diabetic subjects with acrylate dentures and oral Candida spp - Miconazole group<br>These group includes diabetes mellitus patients with acrylate dentures and microbiologically confirmed oral infection caused with Candida spp. These patients were treated with Miconazole gel. | Drug: Miconazole<br>* Protocol for active control groups includes use of Miconazole Oral gel for 14 days with frequency of four time per day.<br>* Other names: Daktanol®;|
| Experimental: Diabetic subjects with acrylate dentures and oral Candida spp - Miconazole and Candberrol group<br>These group includes diabetes mellitus patients with acrylate dentures and microbiologically confirmed oral infection caused with Candida spp. These patients were treated with Miconazole gel and Candberrol lozenges. | Drug: Miconazole<br>* Protocol for active control groups includes use of Miconazole Oral gel for 14 days with frequency of four time per day.<br>* Other names: Daktanol®;Dietary Supplement: CandBerrol® lozenges<br>* Protocol for experimental groups includes use of Miconazole Oral gel and CandBerrol® lozenges for 14 days with frequency of four time per day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of Candida albicans after therapy at first reexamination | Evaluation of symptoms and the presence of Candida spp. on day 18 from the beginning of the therapy | 1.5 year | 
| Presence of Candida albicans after therapy at second reexamination | Evaluation of symptoms and the presence of Candida spp. on day 30 from the beginning of the therapy | 1.5 year | 
| Presence of Candida albicans after therapy at third reexamination | Evaluation of symptoms and the presence of Candida spp. 4 days after the end of the therapy | 1.5 year | 
| Presence of Candida albicans after therapy at fourth reexamination | Evaluation of symptoms and the presence of Candida spp. 12 days after the end of the therapy | 1.5 year |