Effect of a GnRH Analog on Hepatic Steatosis

NCT06523530 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 5221
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Metabolic Dysfunction-Associated Steatotic Liver Disease; Endometriosis; Nonalcoholic Fatty Liver

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Hepatic steatosis

  Ultrasound-Guided Attenuation Parameter (UGAP) measured on an ultrasound machine GE Logiq E10s. Between-within group interactions in UGAP UGAP is a non-invasive index based on the attenuation quantification of the ultrasound beam through the hepatic parenchyma, thus used for hepatic steatosis quantification. Cut-off values of ≥ 0.53 dB/cm/MHz, ≥ 0.60 dB/cm/MHz, and ≥ 0.65 dB/cm/MHz have been proposed for the diagnosis of steatosis grade S1, S2, and S3, respectively

  6 months

• Hepatic fibrosis

  Liver stiffness (LS) measured with 2D Shear Wave Elastography (2D SWE) on an ultrasound machine GE Logiq E10s. Between-within group interactions in LS 2D SWE is a non-invasive tool measuring the hepatic parenchyma stiffness, thus indirectly suggesting fibrosis stage (F). Cut-offs values of \<8.27 kPa, 8.27-9.39 kPa, 9.40-11.88 kPa and ≥11.88 kPa have been proposed for F0-F1, F2, F3, and F4, respectively.

  6 months

Secondary Outcomes (22)

• Liver function tests I - ALT and AST

  6 months

• Liver function tests II - γGT

  6 months

• Insulin resistance

  6 months

• Lipid profile

  6 months

• Non-invasive hepatic steatosis index I - Fatty Liver Index (FLI)

  6 months

Study Arms (2)

Goserelin

EXPERIMENTAL

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

Drug: Goserelin Acetate 3.6 mg inj, implant

Control

NO INTERVENTION

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

Interventions

Goserelin Acetate 3.6 mg inj, implant DRUG

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

Also known as: Zoladex

Goserelin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead
• 424 General Military Hospital: collaborator

Study Sites (2)

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

Thessaloniki, 56403, Greece

RECRUITING

424 General Military Hospital

Thessaloniki, 56429, Greece

RECRUITING

Related Publications (13)

• Henry L, Paik J, Younossi ZM. Review article: the epidemiologic burden of non-alcoholic fatty liver disease across the world. Aliment Pharmacol Ther. 2022 Sep;56(6):942-956. doi: 10.1111/apt.17158. Epub 2022 Jul 26.

  PMID: 35880713 BACKGROUND

• Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, Arrese M, Bataller R, Beuers U, Boursier J, Bugianesi E, Byrne CD, Castro Narro GE, Chowdhury A, Cortez-Pinto H, Cryer DR, Cusi K, El-Kassas M, Klein S, Eskridge W, Fan J, Gawrieh S, Guy CD, Harrison SA, Kim SU, Koot BG, Korenjak M, Kowdley KV, Lacaille F, Loomba R, Mitchell-Thain R, Morgan TR, Powell EE, Roden M, Romero-Gomez M, Silva M, Singh SP, Sookoian SC, Spearman CW, Tiniakos D, Valenti L, Vos MB, Wong VW, Xanthakos S, Yilmaz Y, Younossi Z, Hobbs A, Villota-Rivas M, Newsome PN; NAFLD Nomenclature consensus group. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 Dec 1;78(6):1966-1986. doi: 10.1097/HEP.0000000000000520. Epub 2023 Jun 24.

  PMID: 37363821 BACKGROUND

• Alberti KG, Zimmet P, Shaw J. Metabolic syndrome--a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006 May;23(5):469-80. doi: 10.1111/j.1464-5491.2006.01858.x.

  PMID: 16681555 BACKGROUND

• 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.

  PMID: 35532850 BACKGROUND

• 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.

  PMID: 38760254 BACKGROUND

• 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.

  PMID: 29224098 BACKGROUND

• 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.

  PMID: 29992886 BACKGROUND

• 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.

  PMID: 27225336 BACKGROUND

• 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.

  PMID: 29975553 BACKGROUND

• 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.

  PMID: 23770813 BACKGROUND

• 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.

  PMID: 32151660 BACKGROUND

• 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.

  PMID: 24121382 BACKGROUND

• Pafili K, Paschou SA, Armeni E, Polyzos SA, Goulis DG, Lambrinoudaki I. Non-alcoholic fatty liver disease through the female lifespan: the role of sex hormones. J Endocrinol Invest. 2022 Sep;45(9):1609-1623. doi: 10.1007/s40618-022-01766-x. Epub 2022 Mar 18.

  PMID: 35303270 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Endometriosis; Liver Cirrhosis

Interventions

Goserelin; Drug Implants

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Dimitrios A Anastasilakis, MD, PhDc

  School of Medicine, Aristotle University of Thessaloniki

  STUDY DIRECTOR

• Athina I Gkiomisi, MD, PhD

  424 General Military Hospital, Thessaloniki, Greece

  STUDY DIRECTOR

• Dimitrios G Goulis, MD, PhD

  School of Medicine, Aristotle University of Thessaloniki

  STUDY DIRECTOR

• Angelos Daniilidis, MD, PhD

  School of Medicine, Aristotle University of Thessaloniki

  STUDY DIRECTOR

• Athanasios A Anastasilakis, MD, PhD

  424 General Military Hospital, Thessaloniki, Greece

  STUDY DIRECTOR

• Chrysi Nalmpantidou, MD

  "G. Gennimatas" General Hospital, Thessaloniki, Greece

  STUDY DIRECTOR

• Stergios A Polyzos, MD, PhD

  School of Medicine, Aristotle University of Thessaloniki

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stergios A Polyzos, MD, PhD

CONTACT

2310999316; spolyzos@auth.gr

Dimitrios A Anastasilakis, MD, PhDc

CONTACT

6932238231; dimitanast@auth.gr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pharmacology

Model Details: Multicenter, interventional, open label, non-randomized, parallel group

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 26, 2024
• Study Start: November 26, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: February 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 12 months after the publication of the study.
• Access Criteria: Yet unknown

Locations

GR (2)