A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease

NCT05478083 | Recruiting Phase 2 DMC

• 3 other identifiers: 2020-005949-1610140261910001U1111-1278-8976
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

Multicenter trial on the effect of the GnRH analogue leuprorelin on the growth of total liver volume in pre-menopausal women with very severe polycystic liver disease who, despite available therapy, experience growth and are heading for liver transplantation.

Conditions

Polycystic Liver Disease; Autosomal Dominant Polycystic Kidney

Outcome Measures

Primary Outcomes (1)

• Liver growth

  Liver volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 36 months

  36 months

Secondary Outcomes (16)

• Polycystic liver disease related complaints

  36 months

• Menopause related complaints

  36 months

• Patient reported mental health

  36 months

• Patient reported physical health

  36 months

• Kidney growth

  36 months

Study Arms (2)

Direct start

ACTIVE COMPARATOR

36 months of treatment with study medication

Drug: Leuprorelin

Delayed start

OTHER

First 18 months standard care, hereafter 18 months treatment with study medication

Drug: Leuprorelin

Interventions

Leuprorelin DRUG

Treatment consist of leuprorelin 3.75 mg once monthly for the first 3 months followed by 3-monthly injections of 11.25 mg. The direct start group will use leuprorelin for 36 months. The delayed start group will use standard of care in the first 18 months.

Delayed start; Direct start

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Female hormones, especially estrogen, seem to play a pivotal role in liver growth. More than 90% of patients is female and exogenous estrogen administration enhances liver growth and liver growth declines after menopause.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female patients
• Diagnosis of polycystic liver disease defined as the presence of more than 10 liver cysts
• Age between 18 to 45 (inclusive) years;
• Very large liver for age, defined as the upper 10% of liver volumes in specific age categories (based on a retrospective polycystic liver disease registry, n=1.600 patients)
• yr; height adjusted TLV \> 2.0 L/m
• yr; height adjusted TLV \> 2.2 L/m
• yr; height adjusted TLV \> 2.5 L/m
• years; height adjusted TLV \> 3.0 L/m
• Availability of at least 1 historical MRI or CT scan made between 5 to 1 years before baseline visit of this study
• Ongoing liver growth, defined as an increase in absolute total liver volume between the historical MRI or CT scan and the MRI at screening of this trial
• Since somatostatin analogues are proven efficacious therapy for polycystic liver disease at this time it is required that:
• patients use a somatostatin analogue and still have confirmed liver growth; OR
• patient have a specific reason not to use this medication, .e.g. patient used a somatostatin analogue in the past, but had to stop it due to inefficacy or because he/she did not tolerate it, patient has a contra-indication for using somatostatin analogues, no availability of somatostatin analogues
• Voluntary written informed consent before performance of any study-related procedures not part of standard medical care, and able to read, comprehend, and respond to study questionnaires.

You may not qualify if:

• Post-menopausal status or (vasomotor) symptoms indicating upcoming menopause
• Anti Mullerian Hormone (AMH) measurement at screening visit \<0.03 ng/ml.
• Active desire to have children, pregnancy or breast-feeding
• Contra-indications for leuprorelin, such as history of cardiovascular disease, history of osteoporosis or osteoporosis determined by DEXA-scan at screening (T score ≤ - 2.5), or a known intolerance for leuprorelin
• Liver transplantation or liver surgery expected within 1.5 years, to the discretion of the study doctor
• Contra-indications for MRI assessments (such as implants) or not able or willing to undergo MRI scan for other reasons (e.g. claustrophobia, profound obesity)
• Kidney transplantation or chronic use of immunosuppressive agents (such as cyclosporine, mycophenolic acid, tacrolimus but not prednisolone) for other indications
• Severe hypertension, defined as a systolic blood pressure \>160 mmHg and/or diastolic blood pressure \> 100 mm Hg.
• Clinically significant, uncontrolled medical condition that, in the opinion of the investigator, would put the safety of the patient at risk through participation, or which would affect the efficacy of safety analysis if the condition exacerbated during the study, or that may significantly interfere with study compliance, such as, but not restricted to, recurrent cholangitis, recurrent ascites or hepato-venous outflow obstruction, (history of) depression
• Participation in other interventional studies at the same time.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Radboud University Medical Center: collaborator

Study Sites (2)

Radboudumc

Nijmegen, Gelderland, 6525 GA, Netherlands

NOT YET RECRUITING

Groningen universitair medical center

Groningen, 9713 GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Polycystic liver disease; Polycystic Kidney, Autosomal Dominant

Interventions

Leuprolide

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

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

Central Study Contacts

Ron T Gansevoort

CONTACT

+31 50 3610923; r.t.gansevoort@umcg.nl

Renée Duijzer

CONTACT

renee.duijzer@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Patient blinding is not possible, since leuprorelin will induce menopause related complaints. Primary outcome is not reported to investigators until the study has finished. Outcome assessors are blinded for study subject and treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, controlled trial in which patients are randomized between either 1. Direct start with treatment or 2. Delayed start with treatment which will start after 18 months of standard care with the study medication

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: July 28, 2022
• Study Start: June 1, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: November 4, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (2)