A study into the efficacy and toleratability of leuprorelin by patients suffering from severe polycystic liver disease
- Conditions
- Severe polycystic liver disease in female patientTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2020-005949-16-DE
- Lead Sponsor
- niversity Medical Center Groningen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 36
- 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)
o 18-30 yr; height adjusted TLV > 2.0 L/m
o 30-35 yr; height adjusted TLV > 2.2 L/m
o 35-40 yr; height adjusted TLV > 2.5 L/m
o 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:
o patients use a somatostatin analogue and still have confirmed liver growth; OR
o 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.
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
1. Post-menopausal status or (vasomotor) symptoms indicating upcoming menopause
2. Anti Mullerian Hormone (AMH) measurement at screening visit <0.03 ng/ml.
3. Patients who are pregnant or lactation, or who have an active desire to have children,
pregnancy or breast-feeding during the clinical study
4. A history of osteoporosis or osteoporosis determined by DEXA-scan at screening (T
score = -2.5)
5. Patients diagnosed with a clinical depression and is or has been treated with antidepression medication.
6. Patients known with a prolongated QT time or who use medicinal products leading to
a QT prolongation including, but not restricted to: class IA (e.g. quinidine,
disopyramide) or class III (e.g. amiodarone, sotalol, dofetilide, ibutilide)
antiarrhythmic medicinal products, methadone, moxifloxacin and antipsychotics.
7. Hypersensitivity to leuprorelin or other GnRH analogues, to polylactic acid or
poly(D,L-lactide-co-glycolide) (1:1)
8. Patients with epilepsy which is not well-controlled (defined as manifestation of >= 1
seizure in the last 12 months).
9. Patients with a confirmed hormone independence carcinoma.
10. Liver transplantation or liver surgery expected within 1.5 years, to the discretion of the
study doctor
11. Use of hormonal oral contra-conception containing estrogen and/or progesterone. In
contrast, a hormone containing uterine device is not an exclusion criteria.
12. 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)
13. Kidney transplantation or chronic use of immunosuppressive agents (such as
cyclosporine, mycophenolic acid, tacrolimus but not prednisolone) for other indications
14. Severe hypertension, defined as a systolic blood pressure >160 mmHg and/or diastolic
blood pressure > 100 mm Hg.
15. 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
16. Participation in other clinical trials or treatments with other IMPs and its relevant
metabolites or previous therapies, whose toxicity (may) overlap with that of this
studies IMP and its relevant metabolites within five times the half-life of the drug
and/or metabolites (whichever is longer).
17. Participation in other interventional studies at the same time.
Exclusion criteria related to the historical MRI or CT scan to determine liver
growth before start of the study
- Start or stop of liver volume reducing therapy (medication e.g. somatostatin analogues
or surgical interventions) in the period between the historical scan and the baseline
MRI scan;
- The historical MRI or CT scan is performed <3 months after start or stop of a
somatostatin analogue or surgical volume reducing therapy.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The main objective of this study is to determine whether lowering <br>estrogen and progesterone levels with leuproreline decreases liver <br>growth rates in pre-menopausal women with severe PLD;Secondary Objective: Secondary objectives are to assess in these women the effect of <br>leuproreline on PLD-related complaints, quality of life, tolerability and <br>safety ;Primary end point(s): The primary outcome is the livergrowth, in percent per year, calculated <br>from BL till t=1.5 years, compared between the direct start groep <br>(receiving leuproreline treatment in this period) and the delayed start <br>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 <br>calculated liver growth in percent per year during the first 18 months of <br>the trial, compared between the direct start group and the delayed start <br>group.
- Secondary Outcome Measures
Name Time Method