EndometriosisEarly Phase 1NCT04844996
Antilipidemic Ezetimibe Induces Regression of Endometriotic Explants in a Rat Model of Endometriosis
A Early Phase 1 study testing Surgical induction of endometriotic explants in people with Endometriosis, run by Mersin University at 1 site in Turkey (Türkiye).
Trial summary
Current endometriosis therapy is based on interrupting the menstrual cycle and suppression of estrogen synthesis in order to induce atrophy of endometrial tissue. Progestins, oral contraceptives, androgenic agents, aromatase inhibitors, gonadotropin-releasing hormone analogues all play a role in the treatment of… Read more about this study
- Who is it for?
- Ages 3 to 12 months, women onlyHealthy volunteers can take part
- Conditions the study is for
- Endometriosis
- What is being tested?
- Surgical induction of endometriotic explants
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Sep 2019to 31 Jan 2021
- 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 3 to 12 months
- Women only
- Healthy volunteers accepted
- Child
Who may be able to join
- non-pregnant, sexually mature albino rats weighing between 180-240 g
Who cannot join
- pregnant, non-healthy, sexually immature, weighing <180 g
Trial locations and contacts
1 site in 1 country.
About this study
Current endometriosis therapy is based on interrupting the menstrual cycle and suppression of estrogen synthesis in order to induce atrophy of endometrial tissue. Progestins, oral contraceptives, androgenic agents, aromatase inhibitors, gonadotropin-releasing hormone analogues all play a role in the treatment of endometriosis. However, none of these treatments can definitely cure the disease and they require long-term use despite the side effects of the drug. It is clear that new treatment methods are needed for this disease, and therefore many different new treatment methods are being investigated. Some of the treatment methods have focused on inhibiting angiogenesis and inflammation, which seems to play an important role in the progression of the disease. In the present study, it was investigated whether ezetimibe which is a cholesterol absorption inhibitor with anti-inflammatory and antiangiogenic properties, has therapeutic effect on endometriosis in an experimental rat model.
Read the detailed description
Endometriosis is a relatively common benign disorder that causes significant health problems with yet an unknown etiology. The disease which is defined as the presence of the endometrial gland and stroma outside the uterine cavity, was first described by the famous pathologist Von Rokitansky in 1860. Since then, new theories about the mechanism of its occurrence have been put forward, but no single theory has been holistic enough to explain all clinical presentations of the disease. Retrograde menstruation, stem cell theory, immune system, genetic and environmental factors are among the proposed theories. However, with the widespread use of molecular methods in recent years, more detailed information about its etiopathogenesis has been obtained and new approaches have been proposed for its diagnosis and treatment. Today, it is accepted that multiple factors, including ectopic endometrial tissue, altered immune system response, imbalanced cell proliferation and apoptosis, abnormal endocrine signal and genetic factors, play a role in the pathogenesis of endometriosis, which is a progressive, estrogen-dependent inflammatory disease.
In recent years, studies on the inflammatory and angiogenesis mechanisms that play a role in the pathogenesis of endometriosis have intensified in the treatment of the disease. Agents with anti-inflammatory and antiangiogenic effects have been experimentally shown to partially prevent the formation or reduce the size of endometriotic lesions in animal models. Statins like atorvastatin and simvastatin have been using in the treatment of coronary artery disease with their antilipidemic effects and are shown to have efficacy in animal endometriosis models with their anti-inflammatory and antiangiogenic properties.
Ezetimibe, which is a member of a different class of antilipidemic agents than statins, has similarly been shown to inhibit the release of substances that play a key role in the inflammatory process such as nuclear factor kappa, TNF-α and interleukin 1, and angiogenesis such as VEGF. With this mechanism of action, it may be hypothesized that this agent may have a possible therapeutic effect on endometriosis. Therefore in this study it was aimed to assess the potential therapeutic role of ezetimibe in the experimental rat endometriosis model.
- Conditions
- Endometriosis
- Being tested
- Surgical induction of endometriotic explants
- Keywords
- endometriosis, ezetimibe, antilipidemics
- Medical subject headings
- Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical induction of endometriotic explantsProcedure or surgery
Also called Drug (ezetimibe 1mg/kg/day) and placebo (saline 1 ml/kg/day) administration
Surgical induction of endometriosis was done as: A 5-cm vertical midline incision was made and a distal segment 1 cm in length of the right uterine horn was resected. The segment was split longitudinally, and a 5 X 5 mm piece was sectioned.
This piece of uterine tissue was transplanted without removing the myometrium onto the inner surface of the right abdominal wall with the serosal surface apposed and secured with single nonabsorbable 5-0 polypropylene suture at the middle to the abdominal wall. The abdominal incision was closed in two layers
Drug administration:
Vehicle treatment (1 mL/kg/day saline) was administered orally to the control group with the gavage methodology. Ezetimibe (1 mg/kg/day (Ezetrol®, Merck Sharp Dohme, Istanbul, Turkey) was administered orally with gavage methodology to the rats in the study for 28 days postoperatively
| Study group | Role | What they receive |
|---|---|---|
| Ezetimibe group | Experimental | The endometriosis model was developed surgically in all 18 rats and pretreatment sizes of the endometriotic explants were measured. After randomization Ezetimibe (1 mg/kg/day (Ezetrol®, Merck Sharp Dohme, Istanbul, Turkey) was administered orally with gavage methodology to the 9 rats in the ezetimibe group for 28 days postoperatively. Receives: Procedure: Surgical induction of endometriotic explants |
| Control groups | Placebo comparator | The endometriosis model was developed surgically in all 18 rats and pretreatment sizes of the endometriotic explants were measured. After randomization saline (1 ml/kg/day) was administered orally with gavage methodology to the 9 rats in the control group for 28 days postoperatively. Receives: Procedure: Surgical induction of endometriotic explants |
What is being measured
The primary outcome is the main question the study is designed to answer.
The volume of endometriotic explants in mm3.
The sizes of the explants were measured with a caliber. The spherical volume of each ectopic uterine tissue was calculated using the prolate ellipsoid formula (V [mm3] = 0.52 × width × length × height).
Measured: 3 months
The amount of vascular endothelial growth factor
Immunohistochemical stains were performed with standard protocols. For immunohistochemical evaluation the intensity of the staining in each section was scored as intense (++++), moderate (+++), mild (++), and none (+).
Measured: 5 months
The amount of tumor necrosis factor alpha
Immunohistochemical stains were performed with standard protocols. For immunohistochemical evaluation the intensity of the staining in each section was scored as intense (++++), moderate (+++), mild (++), and none (+).
Measured: 5 months
The number of mast cells
The number of the mast cells stained with toluidine blue was counted under x20 magnification separetely in 5 different areas of the endometrium, myometrium and perimetrium in each specimen (15 different areas in each subject).
Measured: 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2021
- Study start1 Sep 2019
- Primary completion1 Dec 2019
- Study completion31 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- More trials run by Mersin UniversityThe 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
- Single group
- Model description
- an experimental rat, randomized, drug versus placebo trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mersin University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hakan Aytan, Mersin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04844996
- Sponsor's protocol ID
- 992903
- Status last verified
- Apr 2021
- First submitted
- 10 Apr 2021
- Last updated
- 14 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antilipidemic Ezetimibe Induces Regression of Endometriotic Explants in a Rat Model of Endometriosis
- ClinicalTrials.gov ID
- NCT04844996
- Acronym / sponsor ID
- 992903
- Conditions
- Endometriosis
- Keywords
- endometriosis, ezetimibe, antilipidemics
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Mersin UniversityUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 31 Jan 2021 (actual)
- First posted
- 14 Apr 2021 (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.
Current endometriosis therapy is based on interrupting the menstrual cycle and suppression of estrogen synthesis in order to induce atrophy of endometrial tissue. Progestins, oral contraceptives, androgenic agents, aromatase inhibitors, gonadotropin-releasing hormone analogues all play a role in the treatment of endometriosis. However, none of these treatments can definitely cure the disease and they require long-term use despite the side effects of the drug. It is clear that new treatment methods are needed for this disease, and therefore many different new treatment methods are being investigated. Some of the treatment methods have focused on inhibiting angiogenesis and inflammation, which seems to play an important role in the progression of the disease. In the present study, it was investigated whether ezetimibe which is a cholesterol absorption inhibitor with anti-inflammatory and antiangiogenic properties, has therapeutic effect on endometriosis in an experimental rat model.
Detailed description
Endometriosis is a relatively common benign disorder that causes significant health problems with yet an unknown etiology. The disease which is defined as the presence of the endometrial gland and stroma outside the uterine cavity, was first described by the famous pathologist Von Rokitansky in 1860. Since then, new theories about the mechanism of its occurrence have been put forward, but no single theory has been holistic enough to explain all clinical presentations of the disease. Retrograde menstruation, stem cell theory, immune system, genetic and environmental factors are among the proposed theories. However, with the widespread use of molecular methods in recent years, more detailed information about its etiopathogenesis has been obtained and new approaches have been proposed for its diagnosis and treatment. Today, it is accepted that multiple factors, including ectopic endometrial tissue, altered immune system response, imbalanced cell proliferation and apoptosis, abnormal endocrine signal and genetic factors, play a role in the pathogenesis of endometriosis, which is a progressive, estrogen-dependent inflammatory disease.
In recent years, studies on the inflammatory and angiogenesis mechanisms that play a role in the pathogenesis of endometriosis have intensified in the treatment of the disease. Agents with anti-inflammatory and antiangiogenic effects have been experimentally shown to partially prevent the formation or reduce the size of endometriotic lesions in animal models. Statins like atorvastatin and simvastatin have been using in the treatment of coronary artery disease with their antilipidemic effects and are shown to have efficacy in animal endometriosis models with their anti-inflammatory and antiangiogenic properties.
Ezetimibe, which is a member of a different class of antilipidemic agents than statins, has similarly been shown to inhibit the release of substances that play a key role in the inflammatory process such as nuclear factor kappa, TNF-α and interleukin 1, and angiogenesis such as VEGF. With this mechanism of action, it may be hypothesized that this agent may have a possible therapeutic effect on endometriosis. Therefore in this study it was aimed to assess the potential therapeutic role of ezetimibe in the experimental rat endometriosis model.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- an experimental rat, randomized, drug versus placebo trial
| Arm | Type | Receives |
|---|---|---|
| Ezetimibe group | Experimental | Procedure: Surgical induction of endometriotic explantsThe endometriosis model was developed surgically in all 18 rats and pretreatment sizes of the endometriotic explants were measured. After randomization Ezetimibe (1 mg/kg/day (Ezetrol®, Merck Sharp Dohme, Istanbul, Turkey) was administered orally with gavage methodology to the 9 rats in the ezetimibe group for 28 days postoperatively. |
| Control groups | Placebo comparator | Procedure: Surgical induction of endometriotic explantsThe endometriosis model was developed surgically in all 18 rats and pretreatment sizes of the endometriotic explants were measured. After randomization saline (1 ml/kg/day) was administered orally with gavage methodology to the 9 rats in the control group for 28 days postoperatively. |
Who may qualify
- Ages
- 3 to 12 months
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- non-pregnant, sexually mature albino rats weighing between 180-240 g
Key exclusion criteria (1 listed)
- pregnant, non-healthy, sexually immature, weighing <180 g
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 |
|---|---|---|
| Surgical induction of endometriotic explantsAlso: Drug (ezetimibe 1mg/kg/day) and placebo (saline 1 ml/kg/day) administrationSurgical induction of endometriosis was done as: A 5-cm vertical midline incision was made and a distal segment 1 cm in length of the right uterine horn was resected. The segment was split longitudinally, and a 5 X 5 mm piece was sectioned. This piece of uterine tissue was transplanted without removing the myometrium onto the inner surface of the right abdominal wall with the serosal surface apposed and secured with single nonabsorbable 5-0 polypropylene suture at the middle to the abdominal wall. The abdominal incision was closed in two layers Drug administration: Vehicle treatment (1 mL/kg/day saline) was administered orally to the control group with the gavage methodology. Ezetimibe (1 mg/kg/day (Ezetrol®, Merck Sharp Dohme, Istanbul, Turkey) was administered orally with gavage methodology to the rats in the study for 28 days postoperatively | Procedure or surgery | Control groups, Ezetimibe group |
Primary outcome
The volume of endometriotic explants in mm3.
Time frame: 3 months
The sizes of the explants were measured with a caliber. The spherical volume of each ectopic uterine tissue was calculated using the prolate ellipsoid formula (V [mm3] = 0.52 × width × length × height).
The amount of vascular endothelial growth factor
Time frame: 5 months
Immunohistochemical stains were performed with standard protocols. For immunohistochemical evaluation the intensity of the staining in each section was scored as intense (++++), moderate (+++), mild (++), and none (+).
The amount of tumor necrosis factor alpha
Time frame: 5 months
Immunohistochemical stains were performed with standard protocols. For immunohistochemical evaluation the intensity of the staining in each section was scored as intense (++++), moderate (+++), mild (++), and none (+).
The number of mast cells
Time frame: 5 months
The number of the mast cells stained with toluidine blue was counted under x20 magnification separetely in 5 different areas of the endometrium, myometrium and perimetrium in each specimen (15 different areas in each subject).
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 14 Apr 2021.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Surgical induction of endometriotic explants in people with Endometriosis, run by Mersin University at 1 site in Turkey (Türkiye).
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 1 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 14 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 Turkey (Türkiye). 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?
The volume of endometriotic explants in mm3. (time frame: 3 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 14 Apr 2021.