Autosomal Dominant Polycystic Kidney, Polycystic Liver Disease
Conditions
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.
Interventions
DRUGLeuprorelin
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.
Sponsors
Radboud University Medical Center
University Medical Center Groningen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
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.
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
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Liver growth | 36 months | Liver volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 36 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Menopause related complaints | 36 months | Menopause related complaints by using the validated MENQOL questionnaire at baseline, 6 months, 18 months, 24 months and 36 months |
| Patient reported mental health | 36 months | Quality of life and as subset mental health will be measured by the validated RAND SF-36 questionnaires at baseline, 6 months, 18 months, 24 months and 36 months |
| Patient reported physical health | 36 months | Quality of life and as subset physical health will be measured by the validated RAND SF-36 questionnaires at baseline, 6 months, 18 months, 24 months and 36 months |
| Kidney growth | 36 months | Kidney volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 36 months |
| Sex hormone levels | 36 months | Anti Muller Hormone will be assessed at screening. Other Extensive laboratory includes estradiol, progesterone, AMH, FSH, LH levels at baseline, 6 months after start therapy and after 18 and 36 months. |
| Bone density | 36 months | Bone density measured by a DEXA scan at screening, 18 months and 36 months. |
| Renal function | 36 months | eGFR measurements and 24h urine analyisis (in ADPKD patients only) at baseline, 6 months, 18 months, 24 months and 36 months time |
| Polycystic liver disease related complaints | 36 months | PLD related complaints assessed by the Polycystic liver disease-Questionnaire at baseline, 6 months, 18 months, 24 months and 36 months |
| Heart rate | 36 months | Heart rate in beats per minute (measure 3 times with 2 minutes in between) measured at screening, baseline, 3 months, 6 months, 12 months, 18months, 21 months, 24 months, 30 months and 36 months . |
| Weight | 36 months | Body weight in kilograms measured at screening, baseline, 3 months, 6 months, 12 months, 18months, 21 months, 24 months, 30 months and 36 months . |
| Upper-arm-circumference | 36 months | Upper-arm-circumference in centimeters of the non-dominant arm measured at screening, baseline, 3 months, 6 months, 12 months, 18months, 21 months, 24 months, 30 months and 36 months. |
| Abdominal circumference | 36 months | Abdominal circumference in centimeters (measured at the level of the umbilicus) measured at screening, baseline, 3 months, 6 months, 12 months, 18months, 21 months, 24 months, 30 months and 36 months . At screening, length will be collected to calculate Body Mass Index. |
| Length | 1 month | At screening length in centimeters will be collected. |
| The number of participants experciencing a (serious) adverse events | 36 months | During each physical or telephone contact, the adverse effects are queried and registered in accordance with national protocol |
| Symptoms of depression | 36 months | Symptoms of depression measured by the validated BD-II questionnaires at baseline, 6 months, 18 months, 24 months and 36 months |
| Bloodpressure | 36 months | Manual blood pressure measurements in millimetres of mercury (measure 3 times with 2 minutes in between) at screening, baseline, 3 months, 6 months, 12 months, 18months, 21 months, 24 months, 30 months and 36 months . |
Countries
Netherlands
Contacts
Primary ContactRon T Gansevoort
Backup ContactRenée Duijzer
Outcome results
None listed