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Effects of Sulawesi Propolis Extract on Lesion Growth, Apoptotic and Inflammatory Activity of the Rat Endometriosis Tissue

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ClinicalTrials.gov Identifier: NCT04374006
Recruitment Status : Completed
First Posted : May 5, 2020
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
dr Herbert Situmorang,SpOG(K), Indonesia University

Brief Summary:
This study aims to evaluating inflammatory and apoptotic activity in rat's endometriosis lesion treated by Propolis compared to Dienogest

Condition or disease Intervention/treatment Phase
Endometriosis; Peritoneum Endometriosis Drug: Dienogest Drug: Propolis Other: placebo Early Phase 1

Detailed Description:

Propolis has known of having various efficacy. The main benefits are as antimicrobial, antioxidant, anti-inflammatory, immunomodulatory and antiapoptotic.Propolis has even been shown to have an antibacterial effect in vitro, without requiring human immunological reactions.

The immunological effect of propolis is generated through immune suppression directly and decreasing cytokine production which stimulates immune process. Although proven to have a various efficacy, propolis can't be used as a therapeutic drug due to the difficulty of obtaining standard chemical composition as a requirement to be the drug's substances. Therefore, it is necessary to have biological composition in each propolis prepartions written down before comparing the efficacy.

Anti tumor activity by propolis, which has been tested in animal previously, showed that propolis can inhibit DNA synthesis in tumor cells, induce cell apoptosis and activate macrophage to produce factors which regulate the function of B, T, as well as NK cell.

Dienogest, is the next choice of progestin drug class. It has high selectivity binding in progesterone receptors, inhibits cytokine secretion in endometriosis stroma cell and induces apoptosis in endometriosis cell. Dienogest also has slight inhibitory effect against estradiol, so it can deminisce the symptoms due to hypoestrogenic such as decresing in bone mass density.

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Study Type : Interventional
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Tetragonula Aff. Biroi Propolis Extract on Lesion Growth, Apoptotic and Inflammatory Activity of the Rat Endometriosis Tissue
Actual Study Start Date : November 1, 2019
Actual Primary Completion Date : May 18, 2020
Actual Study Completion Date : May 18, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Endometriosis

Arm Intervention/treatment
Experimental: propolis 50
we do sonde everyday to the rat that given treatment of 50mg/kg propolis for 2, 4, and 6 weeks
Drug: Propolis
The propolis contains 20 mg in each ml. So, each rat we given 0,2 ml for 50mg/kg propolis treatment and 0,4 ml for 100mg/kg propolis treatment
Other Name: sulawesian propolis

Experimental: propolis 100
we do sonde everyday to the rat that given treatment of 100mg/kg propolis for 2, 4, and 6 weeks
Drug: Propolis
The propolis contains 20 mg in each ml. So, each rat we given 0,2 ml for 50mg/kg propolis treatment and 0,4 ml for 100mg/kg propolis treatment
Other Name: sulawesian propolis

Active Comparator: dienogest
we do sonde everyday to the rat that given treatment of 25mg/kg dienogest for 2, 4, and 6 weeks
Drug: Dienogest
1mg/kg BW/day based on the study by Katayama et al. A DNG in 0,5% carboxymethylcellulose suspension was given orally with metal sound daily 0,2-0,4 mL per day
Other Name: visanne

Placebo Comparator: water
we do sonde everyday to the rat that given 0,2 ml water placebo for 2, 4, and 6 weeks
Other: placebo
we gave 0,2 ml to each rat everyday to negative control groups, and we gave no treatment to sham groups

Sham Comparator: sham group
after the 2nd laparotomy, we do nothing about sonde, just giving food and drink everyday
Other: placebo
we gave 0,2 ml to each rat everyday to negative control groups, and we gave no treatment to sham groups




Primary Outcome Measures :
  1. mRNA expressions of Bax, Bcl, Cleaved Caspase 3, IL-1B, and PGE 2 [ Time Frame: through study completion, an average of 6 months ]
    The expression of Bax, Bcl-2, ad Caspase 3, IL-1B, PGE2 mRNA was carried out by isolating the RNA samples of endometriosis tissue based on the modified QIAamp RNA Blod Mini Handbook protocol. RNA spectrophotometric measurments and cDNA synthesis were carried out based on the Instruction Manual ReverTra Ace qPCR RT Master Mix with gDNA Remover protocol (Toyobo 2017: 2). In real-time PCR examination, the melting temperature (Tm) was determined to perform Quantitative Real-time PCR (Q-PCR) based on the QuantiTech SYBR Green PCR Handbook protocol (Qiagen 2011: 11) using a 3-step cycling cycle. The results were then compared with the standard curve and analyzed

  2. Mollecular docking [ Time Frame: during the procedure ]
    Twenty-three compounds contained in Propolis were tested by screening using rule of 5 (Lipinski's rule), screening results determine which compounds can enter the body and can work in endometriosis tissue. Furthermore, the three-dimensional shape is made of compounds which have passed the first stage. This process was created using the Marvin Sketch program. Furthermore, the compound that has been formed is stored as a ligand with extension pdb (protein data bank). Look for NFĸB receptor proteins, estrogen A, estrogen B, progesterone A and progesterone B in the protein data bank, which will be stored as protein. Ligands and proteins are tested using standard Lamarckian algorithms in the Autodock program. The results obtained are in the form of bond energy (ΔG), where smaller results indicate a higher likelihood of interaction

  3. Lession size [ Time Frame: during the procedure ]
    In the second laparotomy (before the treatment are given) the investigators take a picture of the lession (as the beginning lession). Then the investigators give the treatment. After the treatment are done, the investigators do the necropsy to take a picture after the treatment was given to compare it with the beginning

  4. The normality of estrus cycle after the treatment [ Time Frame: during the procedure ]
    Vaginal discharge of the rat obtained through vaginal lavage was fixed using 90% alcohol solution and stained using Giemsa. The specimen was examined microscopically to determined its estrous cycle


Secondary Outcome Measures :
  1. Organs morpholgy after the treatment [ Time Frame: through study completion, an average of 6 months ]
    In the necropsy, the investigators take ovarium, uterus, and peritonium to see if there's any change in morphology after the treatment was given



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   we used female rats to make a model of endometriosis
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • female ratus rat type
  • having normal estrus cycle

Exclusion Criteria:

  • nothing

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04374006


Locations
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Indonesia
Animal Laboratory of Indonesia University
Jakarta, Capital Special Region, Indonesia
Sponsors and Collaborators
Indonesia University
Investigators
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Principal Investigator: Wachyu Hadisaputra, Prof, dr, SpOG Lecturer at Obgyn Department, Indonesia University
  Study Documents (Full-Text)

Documents provided by dr Herbert Situmorang,SpOG(K), Indonesia University:
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Responsible Party: dr Herbert Situmorang,SpOG(K), Principal Investigator, Indonesia University
ClinicalTrials.gov Identifier: NCT04374006    
Other Study ID Numbers: 19-10-1269'
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: April 1, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by dr Herbert Situmorang,SpOG(K), Indonesia University:
endometriosis
propolis
Additional relevant MeSH terms:
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Endometriosis
Propolis
Dienogest
Contraceptive Agents, Male
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral
Contraceptive Agents, Female
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Infective Agents