Clinical trial NCT05478083: A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
Official title: A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Polycystic Liver Disease
Autosomal Dominant Polycystic Kidney
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Radboud University Medical Center
First posted: 2022-07-28
Enrollment: 36
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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)

  * 18-30 yr; height adjusted TLV \> 2.0 L/m
  * 30-35 yr; height adjusted TLV \> 2.2 L/m
  * 35-40 yr; height adjusted TLV \> 2.5 L/m
  * 40-45 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.

Exclusion Criteria:

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
* Use of hormonal oral contra-conception containing estrogen and/or progesterone. In contrast, a hormone containing uterine device is not an exclusion criteria.
* 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.

Primary outcomes:
measure: Liver growth
timeFrame: 36 months
Secondary outcomes:
measure: Polycystic liver disease related complaints
timeFrame: 36 months
measure: Menopause related complaints
timeFrame: 36 months
measure: Patient reported mental health
timeFrame: 36 months
measure: Patient reported physical health
timeFrame: 36 months
measure: Kidney growth
timeFrame: 36 months
measure: Sex hormone levels
timeFrame: 36 months
measure: Bone density
timeFrame: 36 months
measure: Renal function
timeFrame: 36 months
measure: Bloodpressure
timeFrame: 36 months
measure: Heart rate
timeFrame: 36 months
measure: Weight
timeFrame: 36 months
measure: Upper-arm-circumference
timeFrame: 36 months
measure: Abdominal circumference
timeFrame: 36 months
measure: Length
timeFrame: 1 month
measure: The number of participants experciencing a (serious) adverse events
timeFrame: 36 months
measure: Symptoms of depression
timeFrame: 36 months
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Groningen
country: Netherlands
facility: Groningen universitair medical center
Study officials:
References: