Antilipidemic Ezetimibe Induces Regression of Endometriotic Explants in a Rat Model of Endometriosis

NCT04844996 | Completed Early Phase 1

• 1 other identifier: 992903
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Endometriosis

Keywords

endometriosis, ezetimibe, antilipidemics

Outcome Measures

Primary Outcomes (4)

• 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).

  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 (+).

  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 (+).

  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).

  5 months

Study Arms (2)

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.

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.

Procedure: Surgical induction of endometriotic explants

Interventions

Surgical induction of endometriotic explants PROCEDURE

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

Also known as: Drug (ezetimibe 1mg/kg/day) and placebo (saline 1 ml/kg/day) administration

Control groups; Ezetimibe group

Eligibility Criteria

• Age: 3 Months - 12 Months
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• non-pregnant, sexually mature albino rats weighing between 180-240 g

You may not qualify if:

• pregnant, non-healthy, sexually immature, weighing \<180 g

Sponsors & Collaborators

• Mersin University: lead

Study Sites (1)

Mersin University

Mersin, 33343, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Endometriosis

Interventions

Pharmaceutical Preparations; Ezetimibe; Sodium Chloride; Organization and Administration

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Health Services Administration

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: the outcome assessors who measured the sizes of the post-treatment explants, and who histopathologically evaluated the explants were blinded to the groups
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr.

Model Details: an experimental rat, randomized, drug versus placebo trial

Study Record Dates

• First Submitted: April 10, 2021
• First Posted: April 14, 2021
• Study Start: September 1, 2019
• Primary Completion: December 1, 2019
• Study Completion: January 31, 2021
• Last Updated: April 14, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)