Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Diseases and Abnormalities at or Before Birth

Digestive System Diseases

Neoplasms

Symptoms and General Pathology

Rare Diseases

Behaviors and Mental Disorders

Kidney Diseases

Polycystic Kidney Diseases

Polycystic Kidney, Autosomal Dominant

Liver Diseases

Cysts

Gastrointestinal Diseases

Pathological Conditions, Anatomical

Autosomal Dominant Multiple Pterygium Syndrome

Quality of Life

Polycystic Liver Disease

Hematinics

All Drugs and Chemicals

Liver Extracts

will receive PLD-Q, EORTC QLQ-30 symptoms subscale, EQ5D-VAS score and SF36

PLD-Q

Marie C Hogan, MD, PhD

Marie C Hogan

Tom Gevers

Patrick Kamath

Jeff Sloan

Joost Drenth

This Pilot study will enable development \& assessment of a Polycystic Liver Disease-specific patient reported outcomes questionnaire (PLD-Q). Polycystic liver disease (PLD) is characterized by the formation of numerous cysts in the liver, and can lead to severe symptomatic hepatomegaly. It is common in patients with autosomal dominant polycystic liver disease (ADPLD) and autosomal dominant polycystic kidney disease (ADPKD).

As liver function is preserved, quality of life is the main outcome in PLD. Patient reported outcomes are increasingly utilized to assess treatment efficacy \& can include any endpoint derived from patient reports \& are usually assessed by questionnaire. Several existing generic questionnaires assess gastrointestinal symptoms, but include irrelevant items for polycystic liver disease (PLD) \& do not examine relevant extra-abdominal symptoms. Also, a questionnaire that assesses the full range of PLD related problems is more likely to be responsive to changes after treatment initiation. Therefore, a tool that accurately detects changes in PLD symptoms is required.

The development and first steps of validation of this questionnaire are already completed in Netherlands. We will further develop this questionnaire for English speaking patients and validate it in Mayo Clinic cohorts.

The study contains three phases. Phase 1: pilot testing of the directly translated questionnaire (from dutch into english) in a small group of polycystic liver disease (PLD) patients. We will include both symptomatic \& asymptomatic patients (i.e. from mild to severe PLD). Phase 2: further refinement of the questionnaire using the results of the pilot test and input of Mayo patient and clinician focus groups. Phase 3: Further validation in a large cohort of 200 PLD patients with (1) comparison with 200 controls without PLD, (2) cross-sectional correlation with total liver (TLV) \& kidney volumes (TKV), (3) comparing ADPKD patients with \& without PLD (5) against other validated questionnaires (e.g. SF36) \& (5) development of a custom "Worry Questionnaire" examining disease-related worries \& concerns. Finally, longitudinal analyses will be performed to assess PLD-Q sensitivity to change in symptoms. Statistical \& psychometric analyses will be provided by Mayo Clinic quality of life Research group, \& developed in accordance with Food and Drug Administration (FDA) guidance on patient-reported outcome measures in consultation with their Study Endpoints \& Labeling Development Division.

Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).

Development and Assessment of the Psychometric Properties of a Polycystic Liver Disease-specific Patient Reported Outcomes Questionnaire (PLD-Q).

measured in patients with autosomal dominant polycystic kidney disease (ADPKD)

Mayo Clinic

Anti-Inflammatory Agents

Antineoplastic Agents

Anti-Infective Agents

Central Nervous System Depressants

Other Dietary Supplements

Prednisone

Mycophenolic Acid

Tacrolimus

Sirolimus

Benzocaine

Temsirolimus

MTOR Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Clotrimazole

Miconazole

Antifungal Agents

Tannic Acid

Tacrolimus, mycophenolate mofetil, and prednisone

Sirolimus, mycophenolate mofetil, and prednisone

Tacrolimus 6-10 mg/day (maintain trough levels of 8-10 ng/mL)

Sirolimus 3-5 mg/day (maintain high-performance liquid chromatography (HPLC) blood level 10-15 ng/mL)

Mycophenolate Mofetil

Patrick Dean, M.D.

QI Qian, MD

The purpose of this study is to see if one kind of immunosuppressive drug has better effects for the patient's polycystic liver disease than another type. Tacrolimus and Sirolimus are the two immunosuppressive drugs that will be compared for this study. Both drugs have been commonly prescribed to prevent rejection.

Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening monogenic disease with a prevalence of 1 in 400-1000 livebirths. ADPKD is caused by mutations to polycystic kidney disease 1 gene (PKD1) (approximately 85% of cases) or polycystic kidney disease 2 gene (PKD2) (the remaining 15%) gene, encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 is a putative cell-surface, receptor-like protein with yet to-be-identified ligand(s), and PC2 a channel protein with a high conductance to Ca2+.

Polycystic liver disease (PLD) is the most common extra-renal manifestation in ADPKD, present in \> 90% of ADPKD patients by age 30. Liver cysts in ADPKD originate from biliary micro-hamartoma or focal proliferations of biliary ductules and from peribiliary glands. Excessive proliferation of biliary epithelial cells, combined with neovascularization, altered cell-extracellular matrix (ECM) interaction/ECM remodeling and cAMP-mediated fluid secretion, is required for the development and expansion of PLD liver cysts.

PLD may become symptomatic with acute complications such as cyst hemorrhage, rupture and infection. Chronic symptoms are frequently associated with massively enlarged PLD, including abdominal distension and pain; dyspnea; gastroesophageal reflux and early satiety which may lead to malnutrition; mechanical lower back pain; obstruction of the inferior vena cava, hepatic and portal veins (leading to dialysis-associated hypotension, hepatic venous outflow obstruction, and portal hypertension) and biliary obstruction. Currently, apart from invasive interventions such as cyst aspiration with sclerosis, cyst fenestration combined hepatic resection and cyst fenestration, liver transplantation and, rarely, selective hepatic artery embolization, no medical therapy is available.

The objective of this study is to conduct a prospective, open-label, randomized trial to examine the effect of sirolimus on total liver volume in kidney transplant recipients with ADPKD.

Four weeks following kidney transplant, subjects will undergo iothalamate clearance measurement, 24-hour urine collection and protein measurement and physical examination by a transplant surgeon. Patients will be randomized to receive either sirolimus-based immunosuppression or to continue tacrolimus-based immunosuppression unless one of the following conditions are noted:

1. Complications of the kidney transplant incision, including, but not limited to: superficial wound infection, deep wound infection, and fascial dehiscence
2. Iothalamate clearance measurement less than 40 mL/min/1.72m\^2
3. Urinary protein excretion greater than 800 mg/24 hours. Subjects with the above conditions will continue to receive tacrolimus-based immunosuppression at the discretion of the treating physician/surgeon.

Enrolled subjects will undergo abdominal and pelvic CT scans within 3 months before or after kidney transplantation and at one, two, and three years after kidney transplantation.

Polycystic Liver Disease in Kidney Transplant

Single Center, Open-label Randomized Prospective Trial: Effect of Sirolimus on Polycystic Liver Disease

Liver volume at 2 years will be compared between the sirolimus and control (tacrolimus) groups using analysis of covariance (ANCOVA).

Wyeth is now a wholly owned subsidiary of Pfizer

Control Group

Sirolimus Group

Total

<=18 years

Between 18 and 65 years

>=65 years

Age Categorical

Female

Male

Gender

United States

Region of Enrollment

This study was terminated due to inadequate enrollment, no data was collected on the participant.

Dr. Patrick G. Dean

Liver Volume at 2 Years After Kidney Transplantation

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).	NCT02173080	Polycystic Live...	PLD-Q	18 Years -	Mayo Clinic
Polycystic Liver Disease in Kidney Transplant	NCT00934791	Polycystic Live...	Tacrolimus Sirolimus Mycophenolate M... Prednisone	18 Years -	Mayo Clinic
Development and Assessment of The Polycystic Liver Disease Questionnaire (PLD-Q).	NCT02173080	Polycystic Live...	PLD-Q	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for autosomal dominant polycystic kidney disease