Severe polycystic liver disease in female patients MedDRA version: 20.1 Level: PT Classification code 10048834 Term: Polycystic liver disease System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10036045 Term: Polycystic kidney System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10036046 Term: Polycystic kidney, autosomal dominant System Organ Clas
Conditions
Interventions
Trade Name: Lucrin
Product Name: Lucrin
Pharmaceutical Form: Solution for infusion in pre-filled syringe
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Female patients with PLD - Age 18 to 45 years - Very large height adjusted liver volume for age: 18-30 yr >2.0 L/m; 30-35 yr >2.2 L/m, 35-40 yr > 2.5 L/m and >40 years >3.0 L/m - Confirmed ongoing liver growth - Since somatostatin analogues are proven efficacious therapy for PLD at this time it is required that patients use a somatostatin analogue and still have liver growth (as mentioned above) or the patient has 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 they did not tolerate it, or they have a contra-indication for using somatostatin analogues) - Availability of at least 1 historical MRI or CT scan made between 5 to 1 years before baseline visit Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Post-menopausal status or (vasomotor) symptoms indicating upcoming menopause; - AMH measurement at screening < 0.3 - Active desire to have pregancy; - Contra-indications for leuproreline, such as history of cardiovascular disease, history of osteoporosis or osteoporosis at the dexa-scan at screening; - Liver transplantation expected in the next 1.5 years - Use of estrogen or progesterone containing medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to determine whether lowering estrogen and progesterone levels with leuproreline decreases liver growth rates in pre-menopausal women with severe PLD.;Secondary Objective: Secondary objectives are to assess in these women the effect of leuproreline on PLD-related complaints, quality of life, tolerability and safety.;Primary end point(s): The primary outcome is the livergrowth, in percent per year, calculated from BL till t=1.5 years, compared between the direct start groep (receiving leuproreline treatment in this period) and the delayed start group (serving as a control group).;Timepoint(s) of evaluation of this end point: At the end of the trial, the primary outcome will be analyzed, using the calculated liver growth in percent per year during the first 18 months of the trial, compared between the direct start group and the delayed start group. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Polycystic liver disease related complaints, using the validated PLD Questionnaire (8). The change in the score on the PLD Questionnaire (? PLD-Q score) will be compared between patients in the direct start group and the delayed start group after 18 months of treatment (? BL-18 months in the direct start group versus ? BL-18 months in the delayed start group) 2. Liver growth rate (in % per year) compared within individuals before start of treatment and during treatment (a paired analysis of growth rates; in the direct start group of historical growth versus growht during the frist 1.5 years of treatment, and in the delayed start group between the first 1.5 years of the trial without treatment and the next 1.5 years of the trial with treatment. Exploratory outcomes: - liver volume, compared between the direct and delayed start groep after 1.5 years - estrogen levels, compared at BL, 3 months after start treatment, 1.5 years, 21 months and 3 years - acute effects of the treatment, using the MRI scans 6 months after start of treatment - safety and toleratability, incidence of (serious) adverse events, bone-density measured using DEXA-scans, drop-out rate - Quality of life, assessed by het SF-36 and BD-II - menopause related complaints, assessed by the MENQOL-questionnaire In patients with polycystic kidney disease - growth rate of kidney volume in the first 1.5 years, compared between the direct start group and delayed start group - growth rate of kidney volumes, compared within individuals, before start of treatment and during treatment - acute effects of the treatment, using the MRI scans 6 months after start of treatment - change in renal function in the first 1.5 years between direct and delayed start group;Timepoint(s) of evaluation of this end point: Endpoints will be evaluated if the last patient fulfulled the trial follow up. For a detailed description of outcomes please see E.5.2.1. | — |
Countries
Germany, Netherlands
Contacts
Public ContactCoordinating investigator
University Medical Center Groningen
Outcome results
None listed