Effect of a GnRH Analog on Hepatic Steatosis

NCT ID: NCT06523530

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-26

Study Completion Date

2027-04-30

Brief Summary

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Menopause increases the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), possibly owing to the abrupt lack of estrogen. Gonadotropin-releasing hormone (GnRH) treatment in endometriosis is regarded as a model of pharmaceutical menopause. Thus, the effect of goserelin acetate, a GnRH analog that results in transient menopause, on hepatic steatosis and fibrosis will be evaluated in this study.

Detailed Description

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The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which until recently was known as nonalcoholic fatty liver disease (NAFLD), has risen to 30% of the global adult general population, whereas the pharmaceutical interventions against it remain limited. Owing to the epidemiologic and pathophysiologic association of MASLD with obesity, type 2 diabetes mellitus, dyslipidemia and arterial hypertension, the diagnostic criteria for MASLD are similar to those of the metabolic syndrome.

Menopause has been associated with higher MASLD prevalence, with the lack of estrogen being a very plausible pathogenetic contributor to this liver disease. Other pathogenetic contributors of MASLD, including abdominal obesity, increase in insulin resistance (IR) and dysmetabolism of carbohydrates and lipids, are aggravated after menopause, thus adversely contributing to the pathogenesis of MASLD. Regarding the effect of the lack of estrogen on the liver, most to date data are derived from experimental studies, largely showing a favoring effect on MASLD. Epidemiological studies have also shown menopause as an associate of MASLD. However, existing clinical studies are mostly observational, thereby not being able to show a causative association between menopause and MASLD.

Gonadotropin-releasing hormone (GnRH) treatment in disorders such as endometriosis can be regarded as a model of pharmaceutical menopause. More specifically, GnRH analogs, like goserelin acetate, lead to pharmaceutical menopause by suppressing the axis hypothalamus-pituitary-ovaries, thus, causing an iatrogenic, reversible ovarian cessation, which lasts as long as the use of GnRH. The adverse effects of GnRH are generally mild and reversible after their discontinuation.

This is a prospective, interventional non-randomized study, which aims to evaluate the effect of goserelin acetate on hepatic steatosis in women with histologically confirmed endometriosis compared with women with endometriosis that will not receive pharmacological treatment post-surgically.

Conditions

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Metabolic Dysfunction-Associated Steatotic Liver Disease Nonalcoholic Fatty Liver Endometriosis

Keywords

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endometriosis goserelin acetate hepatic fibrosis MASLD MASH metabolic dysfunction-associated steatotic liver disease metabolic dysfunction-associated steatohepatitis NAFLD NASH nonalcoholic fatty liver disease nonalcoholic steatohepatitis treatment menopause

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Multicenter, interventional, open label, non-randomized, parallel group
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Goserelin

31 women with histologically confirmed endometriosis will receive goserelin acetate post-surgically.

Group Type EXPERIMENTAL

Goserelin Acetate 3.6 mg inj, implant

Intervention Type DRUG

3.6 mg (1ml) administered subcutaneously once every month for 6 months (totally 6 injections)

Control

31 women with histologically confirmed endometriosis will not receive pharmacological treatment post-surgically.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Goserelin Acetate 3.6 mg inj, implant

3.6 mg (1ml) administered subcutaneously once every month for 6 months (totally 6 injections)

Intervention Type DRUG

Other Intervention Names

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Zoladex

Eligibility Criteria

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Inclusion Criteria

* women of reproductive age
* diagnosis of endometriosis. The disease is suspected by patient's individual history (chronic pelvic pain, dyspareunia or/and dysmenorrhea) and the ultrasonographic imaging (chocolate cysts). The diagnosis is confirmed histologically, after laparoscopic surgical treatment and biopsy sampling, which will be interpreted by an independent blinded pathologist.
* use of contraceptives, which is the first line treatment, is contraindicated or the patient does not consent to receive contraceptives, due to personal preferences.
* written informed consent to participate to the study

Exclusion Criteria

* mean ethanol consumption \>10 g/day
* history of other chronic liver disease (e.g., viral hepatitis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and overlap syndromes, drug-induced liver injury, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency)
* liver cirrhosis
* any malignancy
* chronic kidney disease
* uncontrolled hypothyroidism or hyperthyroidism
* severe sexual hormone disorders (congenital adrenaline hyperplasia, Down syndrome, Turner syndrome).
* use of the following medications within a 12-month period before baseline, which are associated with drug-induced liver injury (DILI): interferon, tamoxifen, amiodarone, aloperidin, glucocorticoids, hormone replacement therapy, contraceptives, anabolic steroids, any medication against tuberculosis, epilepsy or viruses, methotrexate, parenteral nutrition
* use of the following medications within a 12-month period before baseline, which are probably associated with improvement in hepatic steatosis: vitamin E, pioglitazone, insulin, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium- glucose co-transporter-2 inhibitors (SGLT-2i), orlistat, ursodeoxycholic acid
* use of any GnRH agonist or antagonist within a 12-month period before baseline
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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424 General Military Hospital

OTHER

Sponsor Role collaborator

Aristotle University Of Thessaloniki

OTHER

Sponsor Role lead

Responsible Party

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Stergios A Polyzos

Associate Professor of Pharmacology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Dimitrios A Anastasilakis, MD, PhDc

Role: STUDY_DIRECTOR

School of Medicine, Aristotle University of Thessaloniki

Athina I Gkiomisi, MD, PhD

Role: STUDY_DIRECTOR

424 General Military Hospital, Thessaloniki, Greece

Dimitrios G Goulis, MD, PhD

Role: STUDY_DIRECTOR

School of Medicine, Aristotle University of Thessaloniki

Angelos Daniilidis, MD, PhD

Role: STUDY_DIRECTOR

School of Medicine, Aristotle University of Thessaloniki

Athanasios A Anastasilakis, MD, PhD

Role: STUDY_DIRECTOR

424 General Military Hospital, Thessaloniki, Greece

Chrysi Nalmpantidou, MD

Role: STUDY_DIRECTOR

"G. Gennimatas" General Hospital, Thessaloniki, Greece

Stergios A Polyzos, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

School of Medicine, Aristotle University of Thessaloniki

Locations

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424 General Military Hospital

Thessaloniki, Thessaloniki, Greece

Site Status RECRUITING

1st Department of Obstetrics and Gynecology, School of Medicine, Aristotle University of Thessaloniki

Thessaloniki, , Greece

Site Status RECRUITING

Countries

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Greece

Central Contacts

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Stergios A Polyzos, MD, PhD

Role: CONTACT

Phone: 2310999316

Email: [email protected]

Dimitrios A Anastasilakis, MD, PhDc

Role: CONTACT

Phone: 6932238231

Email: [email protected]

Facility Contacts

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Athanasios D Anastasilakis, MD, PhD

Role: primary

Dimitrios A Anastasilakis, MD, PhDc

Role: backup

Athanasios D Anastasilakis, MD, PhD

Role: backup

Dimitrios A Anastasilakis, MD, PhDc

Role: backup

Athina I Gκiomisi, MD, PhD

Role: backup

Dimitrios G Goulis, MD, PhD

Role: primary

Angelos Daniilidis, MD, PhD

Role: backup

Dimitrios G Goulis, MD, PhD

Role: backup

Angelos Daniilidis, MD, PhD

Role: backup

References

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Reference Type BACKGROUND
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Polyzos SA, Lambrinoudaki I, Goulis DG. Menopausal hormone therapy in women with dyslipidemia and nonalcoholic fatty liver disease. Hormones (Athens). 2022 Sep;21(3):375-381. doi: 10.1007/s42000-022-00369-8. Epub 2022 May 9.

Reference Type BACKGROUND
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Polyzos SA, Goulis DG. Menopause and metabolic dysfunction-associated steatotic liver disease. Maturitas. 2024 Aug;186:108024. doi: 10.1016/j.maturitas.2024.108024. Epub 2024 May 14.

Reference Type BACKGROUND
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Palmisano BT, Zhu L, Stafford JM. Role of Estrogens in the Regulation of Liver Lipid Metabolism. Adv Exp Med Biol. 2017;1043:227-256. doi: 10.1007/978-3-319-70178-3_12.

Reference Type BACKGROUND
PMID: 29224098 (View on PubMed)

Venetsanaki V, Polyzos SA. Menopause and Non-Alcoholic Fatty Liver Disease: A Review Focusing on Therapeutic Perspectives. Curr Vasc Pharmacol. 2019;17(6):546-555. doi: 10.2174/1570161116666180711121949.

Reference Type BACKGROUND
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Takaesu Y, Nishi H, Kojima J, Sasaki T, Nagamitsu Y, Kato R, Isaka K. Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis. J Obstet Gynaecol Res. 2016 Sep;42(9):1152-8. doi: 10.1111/jog.13023. Epub 2016 May 26.

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PMID: 27225336 (View on PubMed)

Ferrero S, Evangelisti G, Barra F. Current and emerging treatment options for endometriosis. Expert Opin Pharmacother. 2018 Jul;19(10):1109-1125. doi: 10.1080/14656566.2018.1494154. Epub 2018 Jul 5.

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DiVasta AD, Laufer MR. The use of gonadotropin releasing hormone analogues in adolescent and young patients with endometriosis. Curr Opin Obstet Gynecol. 2013 Aug;25(4):287-92. doi: 10.1097/GCO.0b013e32836343eb.

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Polyzos SA, Kang ES, Boutari C, Rhee EJ, Mantzoros CS. Current and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis. Metabolism. 2020 Oct;111S:154203. doi: 10.1016/j.metabol.2020.154203. Epub 2020 Mar 6.

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Polyzos SA, Kountouras J, Tsatsoulis A, Zafeiriadou E, Katsiki E, Patsiaoura K, Zavos C, Anastasiadou VV, Slavakis A. Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease. Hormones (Athens). 2013 Jul-Sep;12(3):405-16. doi: 10.1007/BF03401306.

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Reference Type BACKGROUND
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Other Identifiers

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5221

Identifier Type: -

Identifier Source: org_study_id