Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- change in insulin sensitivity
研究概览
简要总结
Acromegaly is a rare hormonal disorder leading to increased morbidity and mortality. In the vast majority of cases, a pituitary somatotroph cell adenoma causes excess growth hormone (GH) secretion, leading to hepatic insulin-like-growth factor 1 (IGF-1) hypersecretion. Both the disease as well as its treatment with long-acting somatostatin analogs (LA-SMSA) and/or pegvisomant affect glucose and lipid metabolism, possibly contributing to increased cardiovascular risk.
In this pilot study, the investigators want to explore insulin sensitivity, postprandial gut hormone response, lipid handling and adipocytokine profile in the following 4 groups:
- controlled acromegalic patients on LA-SMSA (group 1)
- controlled acromegalic patients on combination treatment of LA-SMSA and pegvisomant (group 2)
- acromegalic patients without need for medical therapy after surgery (group 3)
- healthy control subjects (group 4)
Furthermore, a longitudinal exploration will be performed in uncontrolled acromegalic patients (i.e. patients with serum IGF-1 levels above age-specific thresholds and/or symptoms due to active acromegaly (excessive sweating , arthralgia)) on LA-SMSA monotherapy (group 5). In this group, insulin sensitivity, postprandial gut hormone response, lipid handling and adipocytokine profile will be explored before introducing pegvisomant and three months after normalisation of IGF-1 levels.
The investigators hypothesize that lipid and glucose handling will be less efficient in the controlled acromegalic patients on LA-SMSA than in controlled patients on combination therapy or after surgery, and that there will be no difference in substrate metabolism between healthy controls and controlled acromegalic patients on combination treatment or after surgery. Further, they hypothesize that introducing pegvisomant in uncontrolled acromegalic patients will improve their postprandial lipid and glucose handling.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Diagnosis of acromegaly over 1 year ago, no changes in treatment schedule since at least 6 months (groups 1-3 and 5) OR healthy volunteer without diagnosis of acromegaly (group 4)
- •Patient is willing to participate and has signed the informed consent
- •Age > 18 years and < 80 years
- •Body Mass Index 18-40 kg/m²
排除标准
- •Biochemistry: liver function tests > 3x ULN; HbA1C > 58 mmol/mol
- •All untreated endocrine disorders including uncontrolled diabetes mellitus type 2 (i.e. HbA1C > 58 mmol/mol)
- •Bariatric surgery; malabsorptive syndromes; hepatic or renal failure
- •Current medication use: insulin, metformin, sulfonylurea, fibrates, incretin mimetics, dopamine agonists (for all but insulin, participation is allowed after a 2- week wash-out period)
- •Abuse of alcohol or drugs
- •Weight changes > 10% of body weight during preceding 12 months
结局指标
主要结局
change in insulin sensitivity
时间窗: before start of pegvisomant and 3 months after normalisation of IGF-1 after start of pegvisomant in group 5
Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM)
insulin sensitivity
时间窗: At enrollment in groups 1-4
Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM)
次要结局
- change in fasting and postprandial glucose(before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5)
- fasting and postprandial glucose(At enrollment in groups 1-4)
- fasting and postprandial insulin(At enrollment in groups 1-4)
- fasting and postprandial gut hormone levels(At enrollment in groups 1-4)
- fasting adipokine levels(At enrollment in group 1-4)
- fasting lipid levels(At enrollment in groups 1-4)
- change in fasting and postprandial gut hormone levels(before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5)
- change in fasting adipokine levels(before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5)
- change in fasting and postprandial insulin levels(before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5)
- change in fasting lipid levels(before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5)