Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

All Conditions

Digestive System Diseases

Neoplasms

Symptoms and General Pathology

Rare Diseases

Polycystic Kidney Diseases

Polycystic Kidney, Autosomal Dominant

Liver Diseases

Cysts

Kidney Diseases

Gastrointestinal Diseases

Kidney Diseases, Cystic

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Congenital Abnormalities

Abnormalities, Multiple

Ciliopathies

Genetic Diseases, Inborn

Pathological Conditions, Anatomical

Autosomal Dominant Multiple Pterygium Syndrome

Menopause

Polycystic Liver Disease

Antineoplastic Agents

Reproductive Control Agents

All Drugs and Chemicals

Hematinics

Leuprolide

Liver Extracts

Antineoplastic Agents, Hormonal

36 months of treatment with study medication

First 18 months standard care, hereafter 18 months treatment with study medication

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.

Leuprorelin

Ron T Gansevoort

Renée Duijzer

Renée Duijzer, msc

Sophie Aapkes

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.

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

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.

Female hormones, especially estrogen, seem to play a pivotal role in liver growth. More than 90% of patients is female and exogenous estrogen administration enhances liver growth and liver growth declines after menopause.

A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease

Liver volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 36 months

PLD related complaints assessed by the Polycystic liver disease-Questionnaire at baseline, 6 months, 18 months, 24 months and 36 months

Menopause related complaints by using the validated MENQOL questionnaire at baseline, 6 months, 18 months, 24 months and 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

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 volumes (in % per year) measured in the MRI at screening, 6 months, 18 months, 24 months and 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 measured by a DEXA scan at screening, 18 months and 36 months.

eGFR measurements and 24h urine analyisis (in ADPKD patients only) at baseline, 6 months, 18 months, 24 months and 36 months time

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 .

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 .

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 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 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.

At screening length in centimeters will be collected.

During each physical or telephone contact, the adverse effects are queried and registered in accordance with national protocol

Symptoms of depression measured by the validated BD-II questionnaires at baseline, 6 months, 18 months, 24 months and 36 months

Radboud University Medical Center

University Medical Center Groningen

Musculoskeletal Diseases

Nervous System Diseases

Arthrogryposis

Joint Diseases

Muscular Diseases

Musculoskeletal Abnormalities

Arthrogryposis Multiplex Congenita

Anti-Infective Agents

Central Nervous System Depressants

Pharmaceutical Solutions

Ethanol

Minocycline

Sclerosing Solutions

Aspiration sclerotherapy is a percutaneous procedure that evacuates fluid from the liver cyst and subsequently exposes cyst lining to a sclerosing agent (e.g. ethanol, minocycline) for a limited period of time.

Laparoscopic fenestration exposes the liver through laparoscopic surgery. During this procedure the cyst is punctured and drained followed by resection of the extra-hepatic cyst wall

aspiration sclerotherapy versus laparoscopic fenestration

Joost P.H. Drenth

Thijs Barten

Radboudumc University M Center

Patients with large hepatic cysts (\> 5cm) may develop symptoms. These can be captured with the polycystic liver disease questionnaire (PLD-Q). Treatment of large hepatic cysts consists of aspiration sclerotherapy or laparoscopic fenestration.

The safety and efficacy of both procedures has been explored in two recent systematic reviews yet no evident conclusion regarding superiority of either procedure could be drawn.

The main objective of the ATLAS trial is to compare laparoscopic fenestration and aspiration sclerotherapy in patients with large symptomatic hepatic cysts on patient-reported outcomes.

Rationale: Patients with large hepatic cysts(\>5cm) may develop symptoms due to distention of Glisson's capsule and/or compression on other abdominal organs. Frequently reported symptoms include abdominal pain, early satiety, nausea, and dyspnea. These symptoms can be captured in the disease-specific Polycystic Liver Disease Questionnaire (PLD-Q), a validated instrument. The treatment of symptomatic liver cysts is aimed to improve symptoms and quality of life by reducing cyst volume. There are two procedures available to treat symptomatic liver cysts: percutaneous aspiration sclerotherapy and laparoscopic fenestration.

In aspiration sclerotherapy, fluid is evacuated from the liver cyst and subsequently the cyst lining is exposed to a sclerosing agent for a limited period of time. Sclerotherapy causes temporary recurrence of cyst fluid after drainage, but subsequently results in a steady decrease of cyst volume in the majority of patients.

In laparoscopic fenestration the liver is exposed through laparoscopic surgery. In this procedure the cyst is punctured and drained followed by resection of extra-hepatic cyst wall.

The safety and efficacy of aspiration sclerotherapy and laparoscopic fenestration have been explored in two recent systematic reviews. No evident conclusion could be drawn because of the retrospective study design in the vast majority of the studies and the heterogeneity among these. A randomized controlled trial is warranted to identify the possible differences in safety and efficacy in aspiration sclerotherapy and laparoscopic fenestration.

Hypothesis: The investigators expect patients treated with laparoscopic fenestration to have better clinical outcome; i.e. a lower PLD-Q score, compared to aspiration sclerotherapy, when measured 4 weeks after the procedure. The investigators expect this difference to become smaller over time (after 6 and 12 months), with loss of statistical significance.

Objective: The main objective is to compare laparoscopic fenestration and aspiration sclerotherapy in patients with large symptomatic hepatic cysts on patient-reported outcomes. This information can be used to assess cost-effectiveness in both treatments.

Study design: A prospective, randomized clinical superiority trial in which patients will be randomized 1:1 to one of the treatment arms. Patients will be followed for 1 year.

Study population: All patients ≥18 years who are diagnosed with a dominant, simple hepatic cyst (\>5 cm in diameter), that are symptomatic (PLD-Q score ≥20) and have an indication for treatment (both aspiration sclerotherapy and laparoscopic fenestration) are suitable for inclusion in this study. Only patients that are eligible for both treatments can be included in this study. In particular, patients with multiple cysts (\>20 cysts of \>1.5 cm) will be excluded as surgery leads to more complications in these patients.

Intervention: Patients will be randomly allocated to either aspiration sclerotherapy or laparoscopic fenestration. Both procedures are performed according to the standard Radboudumc protocols. Aspiration sclerotherapy consists of ultrasound-guided, percutaneous drainage of the cyst with subsequent sclerosation with ethanol. Laparoscopic fenestration consists of standard abdominal laparoscopy in which the large cyst(s) are drained and deroofed.

Main study parameters: The main study parameter is the PLD-Q score at 4 weeks after treatment. Secondary parameters are among others: PLD-Q score at baseline, 6 months and 12 months; liver volume (CT) at baseline and 4 weeks; cyst volume (ultrasound) at baseline, 4 weeks, 6 months and 12 months; complications according to Clavien-Dindo; admission duration, recurrence and re-intervention rates.

Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts

Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts (ATLAS): a Randomized Clinical Trial.

Individual participant data are available to other researchers for clinical research purposes upon reasonable request to the principal investigator

Comparison of PLD-Q scores 4 weeks after the procedure, adjusted for baseline PLD-Q score.

PLD-Q score at 1, 6 and 12 months after intervention, adjusted for baseline

PLD-Q individual symptom scores at 1, 6 and 12 months after intervention, compared to baseline

SF-36 Mental Component Score at 1, 6 and 12 months after intervention, adjusted to baseline

SF-36 Physical Component Score at 1, 6 and 12 months after intervention, adjusted to baseline

EQ-5D-5L score at 1, 6 and 12 months after intervention, adjusted to baseline

Liver and cyst volume with CT before and 12 months after the intervention

Liver and cyst volume in cases of recurrence of symptoms

Cyst volume with ultrasound, at baseline and 1, 6 and 12 months after intervention.

Adverse events (according to Clavien-Dindo)

Re-intervention rates during 12 months follow-up.

Cost-effectiveness of both procedures iPCQ 1, 6 and 12 months after intervention, adjusted for baseline

Cost-effectiveness of both procedures iMCQ 1, 6 and 12 months after intervention, adjusted for baseline

Cassie Howe, CRC

Marie C Hogan, MD, PhD

Marie C. Hogan, M.D., Ph.D.

Marie Hogan, MD, PhD

An observational prospective study to determine the impact of foam sclerotherapy of large, dominant kidney/liver cysts on quality of life outcomes and kidney/liver cyst volumes at up to 12 months of follow-up in patients with autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD).

Cyst burden is an important determinant of outcomes in both autosomal dominant polycystic kidney disease (ADPKD) (1, 2) and autosomal dominant polycystic liver disease (ADPLD) (3, 4). Furthermore, mass symptoms (from liver and kidney volume) greatly impact upon quality of life in patients with severe disease. Cyst volume increases exponentially with age and results in the development of end-stage renal disease and hypertension, compromised quality of life due to compressive symptoms, and predisposes patients to cyst complications such as infection, hemorrhage, rupture, and torsion. Existing percutaneous treatments for cyst burden in ADPKD and ADPLD include cyst aspiration with or without sclerotherapy. Although frequently effective in the short-term, recurrence rates and the need for repeat procedures are high after these procedures (5, 6). Extrarenal disease (primarily liver disease) is the most important aspect of disease burden to ADPKD patients (7), and there are few effective treatments.

Foam sclerotherapy (FS) with 3% Sodium Tetradecyl Sulfate (STS) a sclerosing agent. (Sotradecol®; Mylan, Galway, Ireland) is approved by the FDA for the management of varicose veins. While increasing cyst burden significantly compromises quality of life, the impact of FS on patient-reported outcomes has not been evaluated. In collaboration with the Center for Science of Healthcare delivery, we have developed a patient-reported outcome tool for polycystic liver disease capable of detecting symptom burden in individuals with polycystic liver disease that has been approved by the FDA as a patient-reported outcomes tool in research. Furthermore measurement of liver and kidney volumes can be performed in the Polycystic Kidney Disease Imaging Research Core that monitors organ volumes before and after interventions. At this time, patients are interested in procedures that will alleviate and palliate their mass symptoms but desire preliminary information on the procedural efficacy. We aim to report our experience with a new therapeutic advance - FS for the treatment of liver and kidney cysts at Mayo Clinic - and to determine the impact of this procedure on patient-reported quality of life measures and changes in organ volumes.

A Prospective Observational Study of Foam Sclerotherapy .

A Prospective Observational Study of Foam Sclerotherapy for the Treatment of Symptomatic Kidney or Liver Cysts in Patients With Autosomal Dominant Polycystic Kidney and Liver Disease.

Measured using self assessed brief pain inventory (short form) questionnaire, using a scale of 0 is no pain and 10 is pain as bad as you can imagine

Measured using the linear analogue self assessed questionnaire, using a scale of 0 is as bad as it can be and 10 is as good as it can be

Measured using the self assessed Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), using a scale that ranges from yes and no or all of the time to none of the time

Measured using the self assessed Polycystic Liver Disease Questionnaire, using a scale that ranges from never/not at all to always/a lot

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A GnRH Agonist IN Pre-menopausal Women STudy to Treat Severe Polycystic Liver Disease	NCT05478083	Polycystic Live... Autosomal Domin...	Leuprorelin	18 Years - 45 Years	University Medical Center Groningen
Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts	NCT05500157	Liver Cyst Polycystic Live... Autosomal Domin... Autosomal Domin...	aspiration scle...	18 Years - 75 Years	Radboud University Medical Center
A Prospective Observational Study of Foam Sclerotherapy .	NCT04111692	Autosomal Domin... Renal Cyst Autosomal Domin... Hepatic Cyst		18 Years - 100 Years	Mayo Clinic
Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts	NCT05500157	Liver Cyst Polycystic Live... Autosomal Domin... Autosomal Domin...	aspiration scle...	18 Years - 75 Years	Radboud University Medical Center
A Prospective Observational Study of Foam Sclerotherapy .	NCT04111692	Autosomal Domin... Renal Cyst Autosomal Domin... Hepatic Cyst		18 Years - 100 Years	Mayo Clinic

Spots Global Cancer Trial Database for autosomal dominant polycystic kidney