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

Обзор

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.

Вмешательства

• Препарат Leuprorelin
  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.

Первичные конечные точки

• Liver growth [Срок оценки: 36 months]

Вторичные конечные точки (12)

• Polycystic liver disease related complaints [Срок оценки: 36 months]
• Menopause related complaints [Срок оценки: 36 months]
• Patient reported mental health [Срок оценки: 36 months]
• Patient reported physical health [Срок оценки: 36 months]
• Kidney growth [Срок оценки: 36 months]
• Sex hormone levels [Срок оценки: 36 months]
• Bone density [Срок оценки: 36 months]
• Renal function [Срок оценки: 36 months]
• Bloodpressure [Срок оценки: 36 months]
• Heart rate [Срок оценки: 36 months]
• Weight [Срок оценки: 36 months]
• Upper-arm-circumference [Срок оценки: 36 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Нидерланды · 2 центра

• Radboudumc — Nijmegen
• Groningen universitair medical center — Groningen

Идентификаторы

NCT: NCT05478083 · 2020-005949-16 · 2020-005949-16 · 10140261910001 · U1111-1278-8976

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗