Endometriosis; PeritoneumEarly Phase 1NCT04374006
Effects of Sulawesi Propolis Extract on Lesion Growth, Apoptotic and Inflammatory Activity of the Rat Endometriosis Tissue
A Early Phase 1 study testing Dienogest and Propolis in people with Endometriosis; Peritoneum and Endometriosis, run by Universitas Indonesia at 1 site in Indonesia.
Trial summary
This study aims to evaluating inflammatory and apoptotic activity in rat's endometriosis lesion treated by Propolis compared to Dienogest Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Endometriosis; Peritoneum, Endometriosis
- What is being tested?
- Dienogest and Propolis
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteIndonesia
- Study dates
- 1 Nov 2019to 18 May 2020
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- female ratus rat type
- having normal estrus cycle
Who cannot join
- nothing
Trial locations and contacts
1 site in 1 country.
Indonesia1 site
Animal Laboratory of Indonesia University
Jakarta, Capital Special Region
About this study
Official title: Effects of Tetragonula Aff. Biroi Propolis Extract on Lesion Growth, Apoptotic and Inflammatory Activity of the Rat Endometriosis Tissue
This study aims to evaluating inflammatory and apoptotic activity in rat's endometriosis lesion treated by Propolis compared to Dienogest
Read the 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.
- Conditions
- Endometriosis; Peritoneum, Endometriosis
- Being tested
- Dienogest, Propolis, placebo
- Keywords
- endometriosis, propolis
- Medical subject headings
- Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DienogestDrug
Also called visanne
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
PropolisDrug
Also called sulawesian 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
placeboOther
we gave 0,2 ml to each rat everyday to negative control groups, and we gave no treatment to sham groups
| Study group | Role | What they receive |
|---|---|---|
| propolis 50 | Experimental | we do sonde everyday to the rat that given treatment of 50mg/kg propolis for 2, 4, and 6 weeks Receives: Drug: Propolis |
| propolis 100 | Experimental | we do sonde everyday to the rat that given treatment of 100mg/kg propolis for 2, 4, and 6 weeks Receives: Drug: Propolis |
| dienogest | Active comparator | we do sonde everyday to the rat that given treatment of 25mg/kg dienogest for 2, 4, and 6 weeks Receives: Drug: Dienogest |
| water | Placebo comparator | we do sonde everyday to the rat that given 0,2 ml water placebo for 2, 4, and 6 weeks Receives: Other: placebo |
| sham group | Sham comparator | after the 2nd laparotomy, we do nothing about sonde, just giving food and drink everyday Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
mRNA expressions of Bax, Bcl, Cleaved Caspase 3, IL-1B, and PGE 2
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
Measured: through study completion, an average of 6 months
Mollecular docking
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
Measured: during the procedure
Lession size
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
Measured: during the procedure
The normality of estrus cycle after the treatment
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
Measured: during the procedure
Secondary outcomes (1)
Organs morpholgy after the treatment
In the necropsy, the investigators take ovarium, uterus, and peritonium to see if there's any change in morphology after the treatment was given
Measured: through study completion, an average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start1 Nov 2019
- Primary completion18 May 2020
- Study completion18 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endometriosis; PeritoneumStudies of the same condition, open and under way.
- More trials run by Universitas IndonesiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, dr Herbert Situmorang,SpOG(K), Universitas Indonesia
- Investigators
- Wachyu Hadisaputra, Prof, dr, SpOG, Principal investigator, Lecturer at Obgyn Department, Indonesia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04374006
- Sponsor's protocol ID
- 19-10-1269'
- Status last verified
- Mar 2021
- First submitted
- 21 Apr 2020
- Last updated
- 1 Apr 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Tetragonula Aff. Biroi Propolis Extract on Lesion Growth, Apoptotic and Inflammatory Activity of the Rat Endometriosis Tissue
- ClinicalTrials.gov ID
- NCT04374006
- Acronym / sponsor ID
- 19-10-1269'
- Conditions
- Endometriosis; Peritoneum, Endometriosis
- Keywords
- endometriosis, propolis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Universitas IndonesiaUniversity, hospital or other
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- 18 May 2020 (actual)
- Study completion
- 18 May 2020 (actual)
- First posted
- 5 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to evaluating inflammatory and apoptotic activity in rat's endometriosis lesion treated by Propolis compared to Dienogest
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| propolis 50 | Experimental | Drug: Propoliswe do sonde everyday to the rat that given treatment of 50mg/kg propolis for 2, 4, and 6 weeks |
| propolis 100 | Experimental | Drug: Propoliswe do sonde everyday to the rat that given treatment of 100mg/kg propolis for 2, 4, and 6 weeks |
| dienogest | Active comparator | Drug: Dienogestwe do sonde everyday to the rat that given treatment of 25mg/kg dienogest for 2, 4, and 6 weeks |
| water | Placebo comparator | Other: placebowe do sonde everyday to the rat that given 0,2 ml water placebo for 2, 4, and 6 weeks |
| sham group | Sham comparator | Other: placeboafter the 2nd laparotomy, we do nothing about sonde, just giving food and drink everyday |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- female ratus rat type
- having normal estrus cycle
Key exclusion criteria (1 listed)
- nothing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DienogestAlso: visanne1mg/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 | Drug | dienogest |
| PropolisAlso: sulawesian propolisThe 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 | Drug | propolis 100, propolis 50 |
| placebowe gave 0,2 ml to each rat everyday to negative control groups, and we gave no treatment to sham groups | Other | sham group, water |
Primary outcome
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
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
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
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
1 secondary outcome
Organs morpholgy after the treatment
Time frame: through study completion, an average of 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wachyu Hadisaputra, Prof, dr, SpOG principal investigator
Lecturer at Obgyn Department, Indonesia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Dienogest and Propolis in people with Endometriosis; Peritoneum and Endometriosis, run by Universitas Indonesia at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mRNA expressions of Bax, Bcl, Cleaved Caspase 3, IL-1B, and PGE 2 (time frame: through study completion, an average of 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.