Metabolic Outcomes in Patients With Prolactinomas Under Dopamine Agonist Treatment

Официальное название

Metabolic Outcomes in Patients With Prolactinomas Under Dopamine Agonist Treatment - A Randomized, Single-Blind Active- Controlled Trial

Обзор

This randomized, active-controlled, parallel-arm, single-blind trial is to compare the effects of Dopamine agonists (DA) therapy targeting different established treatment strategies on glucose metabolism assessed by an oral glucose tolerance test.

Подробное описание

Prolactinomas are the most common pituitary tumors, leading to hyperprolactinemia, which causes hypogonadism, infertility, and is associated with adverse metabolic effects such as insulin resistance, dyslipidemia, and obesity. Dopamine agonists (DAs), especially cabergoline, are the first-line treatment. They reduce prolactin levels and tumor size effectively. Despite their widespread use, there are no evidence-based guidelines regarding target prolactin levels during DA therapy. Limited evidence suggests that different prolactin levels may have different effects on metabolic health. This trial aims to assess glucose tolerance, insulin sensitivity, and beta-cell function-using OGTT with insulin levels-after 12 months of DA treatment, to target treatment options.

In Switzerland, cabergoline is the preferred DAs for treating hyperprolactinemia.

Cabergoline is available in tablet form, with doses of 0.5 mg per tablet. The standard dosing for hyperprolactinemia typically starts at 0.25 mg to 0.5 mg per week, which can be gradually increased based on the patient's response, with a usual range of 0.25 mg to 2 mg per week.

Вмешательства

• Препарат Cabergoline (Dopamine Agonist)
  Cabergoline is available in tablet form, with doses of 0.5 mg per tablet. The standard dosing for hyperprolactinemia typically starts at 0.25 mg to 0.5 mg per week, which can be gradually increased based on the patient's response, with a usual range of 0.25 mg to 2 mg per week. The dose required to achieve the target prolactin levels (pre- defined for each intervention arm) may vary between patients, so a fixed dose is not specified. This allows for individualized treatment based on each patient

Первичные конечные точки

• 2-hour post-oral glucose tolerance test (OGTT) plasma glucose levels [Срок оценки: assessed at 12 months after randomisation]

Вторичные конечные точки (9)

• Change in Insulin sensitivity by MATSUDA Index [Срок оценки: measured at time points (0, 30, 60, 90, and 120 minutes) during the OGTT]
• Change in Insulin Sensitivity Index (ISI) [Срок оценки: measured at time points (0, 30, 60, 90, and 120 minutes) during the OGTT]
• Change in Quantitative Insulin Sensitivity Check Index (QUICKI) [Срок оценки: measured at time points Screening, Month 6, Month 12, Month 24]
• Change in Glycated Haemoglobin (HbA1c) [Срок оценки: measured at time points Screening, Month 3, Month 6, Month 12]
• Change in Fasting glucose (mmol/L) [Срок оценки: measured at time points Screening, Month 3, Month 6, Month 12]
• Change in Fasting insulin (µU/mL) [Срок оценки: measured at time points Screening, Month 3, Month 6, Month 12]
• Change in C-peptide (nmol/l) [Срок оценки: measured at time points Screening, Month 3, Month 6, Month 12]
• Change in Disposition Index (DI) [Срок оценки: measured at time points Screening, Month 3, Month 6, Month 12]
• Change in plasma prolactin levels (ng/mL) [Срок оценки: measured at time points Screening, Month 3, Month 6, Month 12]

Критерии участия

Inclusion Criteria (treatment-naïve patients):

• Diagnosed adult patients (at least 18 years of age) with prolactinoma-induced hyperprolactinemia, defined as a prolactin level ≥ two times the local laboratory maximum and radiographic criteria, based on current guidelines.

Inclusion Criteria (treatment-naïve patients):

• Diagnosed adult patients (at least 18 years of age) with prolactinoma-induced hyperprolactinaemia based on current guidelines.
• Patients treated with cabergoline as DA therapy and prolactin levels within the normal range

Критерии исключения

• alternative explanation for hyperprolactinaemia
• Active substance use disorder within the last six months
• Current or previous psychotic disorder
• Pregnancy or breastfeeding within the last 8 weeks
• Severe hepatic insufficiency or cholestasis

• Child Pugh C or
• AST/ ALT > 3 x the upper limit of normal ULN or
• Cholestasis (total bilirubin > 2x ULN)
• Severe renal impairment (eGFR < 30 ml/min)
• History of pulmonary, pericardial, and/or retroperitoneal fibrotic disorders
• Concomitant treatment with strong or moderate CYP3A4 inhibitors
• Local complications on morphological imaging, related to signs or clinical symptoms which make surgical intervention necessary or a clear patient's preference for surgical treatment
• Gastrointestinal disease or previous surgery: chronic active inflammatory bowel disease, active gastrointestinal ulcer disease, or surgery on the gastrointestinal tract (e.g. sleeve stomach, gastric band)
• Patient incapable of giving informed consent due to cognitive impairment or other reasons (e.g., legal incapacity)

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Швейцария · 1 центр

• University Hospital Basel, Dept. of Endocrinology, Metabolism & Diabetes — Basel

Идентификаторы

NCT: NCT07045935 · 2025-00829; kt25Atila

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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