Polycystic Liver DiseasePhase 2AGAINST-PLDNCT05478083
A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
A Phase 2 study testing Leuprorelin in people with Polycystic Liver Disease and Autosomal Dominant Polycystic Kidney, run by University Medical Center Groningen at 2 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Polycystic Liver Disease, Autosomal Dominant Polycystic Kidney
- What is being tested?
- Leuprorelin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesNetherlands
- Study dates
- 1 Jun 2022to 1 Oct 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Renée Duijzer contact
Netherlands2 sites, 2 recruiting
- Recruiting
Groningen universitair medical center
Groningen, 9713 GZ
Renée Duijzer, msc, +31(0)629669242, r.duijzer@umcg.nl
Sophie Aapkes, s.e.aapkes@umcg.nl
- Not yet recruiting
Radboudumc
Nijmegen, Gelderland, 6525 GA
Renée Duijzer, +31(0)629669242, renee.duijzer@radboudumc.nl
About this study
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.
- Being tested
- Leuprorelin
- Medical subject headings
- Polycystic liver disease, Polycystic Kidney, Autosomal Dominant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeuprorelinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Direct start | Active comparator | 36 months of treatment with study medication Receives: Drug: Leuprorelin |
| Delayed start | Other | First 18 months standard care, hereafter 18 months treatment with study medication Receives: Drug: Leuprorelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver growth
Liver volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 36 months
Measured: 36 months
Secondary outcomes (16)
Polycystic liver disease related complaints
PLD related complaints assessed by the Polycystic liver disease-Questionnaire at baseline, 6 months, 18 months, 24 months and 36 months
Measured: 36 months
Menopause related complaints
Menopause related complaints by using the validated MENQOL questionnaire at baseline, 6 months, 18 months, 24 months and 36 months
Measured: 36 months
Patient reported mental health
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
Measured: 36 months
Patient reported physical health
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
Measured: 36 months
Kidney growth
Kidney volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 36 months
Measured: 36 months
Sex hormone levels
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.
Measured: 36 months
Bone density
Bone density measured by a DEXA scan at screening, 18 months and 36 months.
Measured: 36 months
Renal function
eGFR measurements and 24h urine analyisis (in ADPKD patients only) at baseline, 6 months, 18 months, 24 months and 36 months time
Measured: 36 months
Bloodpressure
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 .
Measured: 36 months
Heart rate
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 .
Measured: 36 months
Weight
Body weight in kilograms measured at screening, baseline, 3 months, 6 months, 12 months, 18months, 21 months, 24 months, 30 months and 36 months .
Measured: 36 months
Upper-arm-circumference
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.
Measured: 36 months
Abdominal circumference
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.
Measured: 36 months
Length
At screening length in centimeters will be collected.
Measured: 1 month
The number of participants experciencing a (serious) adverse events
During each physical or telephone contact, the adverse effects are queried and registered in accordance with national protocol
Measured: 36 months
Symptoms of depression
Symptoms of depression measured by the validated BD-II questionnaires at baseline, 6 months, 18 months, 24 months and 36 months
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2022
- Study start1 Jun 2022
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Radboud University Medical Center
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05478083
- Sponsor's protocol ID
- 2020-005949-16
- Other IDs
- 2020-005949-16, 10140261910001, U1111-1278-8976
- Acronym
- AGAINST-PLD
- Status last verified
- Nov 2022
- First submitted
- 9 May 2022
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease
- ClinicalTrials.gov ID
- NCT05478083
- Acronym / sponsor ID
- AGAINST-PLD / 2020-005949-16
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Radboud University Medical Center
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Oct 2027 (estimated)
- First posted
- 28 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Direct start | Active comparator | Drug: Leuprorelin36 months of treatment with study medication |
| Delayed start | Other | Drug: LeuprorelinFirst 18 months standard care, hereafter 18 months treatment with study medication |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- 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)
- Availability of at least 1 historical MRI or CT scan made between 5 to 1 years before baseline visit of this study
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LeuprorelinTreatment 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. | Drug | Delayed start, Direct start |
Primary outcome
Liver growth
Time frame: 36 months
Liver volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 36 months
16 secondary outcomes
Polycystic liver disease related complaints
Time frame: 36 months
Menopause related complaints
Time frame: 36 months
Patient reported mental health
Time frame: 36 months
Patient reported physical health
Time frame: 36 months
Kidney growth
Time frame: 36 months
Sex hormone levels
Time frame: 36 months
Bone density
Time frame: 36 months
Renal function
Time frame: 36 months
Bloodpressure
Time frame: 36 months
Heart rate
Time frame: 36 months
Weight
Time frame: 36 months
Upper-arm-circumference
Time frame: 36 months
Abdominal circumference
Time frame: 36 months
Length
Time frame: 1 month
The number of participants experciencing a (serious) adverse events
Time frame: 36 months
Symptoms of depression
Time frame: 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Individual participant dataSharing planned: No
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Polycystic Liver Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Renée Duijzer contact
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Leuprorelin in people with Polycystic Liver Disease and Autosomal Dominant Polycystic Kidney, run by University Medical Center Groningen at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ron T Gansevoort (+31 50 3610923, r.t.gansevoort@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liver growth (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.