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NCT Number: NCT02152124

Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?

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.

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Key information

Conditions

Acromegaly Bone Diseases Bone Diseases, Endocrine Brain Diseases Central Nervous System Diseases Endocrine System Diseases Glucose Metabolism Disorders Hyperinsulinism Hyperpituitarism Hypothalamic Diseases Insulin Resistance Metabolic Diseases Musculoskeletal Diseases Nervous System Diseases Nutritional and Metabolic Diseases Pituitary Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Ghent University Hospital, Department of Endocrinology, 9K12IE

Ghent, 9000, Belgium

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

Primary outcomes

  1. change in insulin sensitivity

    Time frame: 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)

  2. insulin sensitivity

    Time frame: 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)

Secondary outcomes

  1. fasting and postprandial glucose

    Time frame: At enrollment in groups 1-4

    Serum glucose levels during mixed-meal test (before and 10, 30, 60, 120, 180, 240, 300 minutes after ingestion of standard mixed-meal (bread, margarine, cheese and milk) providing a caloric content of 1000 kCal whereby 45% of the energy comes from fat, 36% from carbohydrates and 19% from proteins)

  2. fasting and postprandial insulin

    Time frame: At enrollment in groups 1-4

    Insulin levels during standard mixed-meal test (cfr.supra)

  3. fasting and postprandial gut hormone levels

    Time frame: At enrollment in groups 1-4

    Serum levels of gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1 (GLP-1), oxyntomodulin and cholecystokinin before start during standard mixed-meal test (cfr.supra)

  4. fasting adipokine levels

    Time frame: At enrollment in group 1-4

    Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6)

  5. fasting lipid levels

    Time frame: At enrollment in groups 1-4

    Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol

  6. change in fasting and postprandial glucose

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

    Serum glucose levels during mixed-meal test (before and 10, 30, 60, 120, 180, 240, 300 minutes after ingestion of standard mixed-meal (bread, margarine, cheese and milk) providing a caloric content of 1000 kCal whereby 45% of the energy comes from fat, 36% from carbohydrates and 19% from proteins)

  7. change in fasting and postprandial insulin levels

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

    Insulin levels during standard mixed-meal test (cfr.supra)

  8. change in fasting and postprandial gut hormone levels

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

    Serum levels of gastric inhibitory polypeptide (GIP), ghrelin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1 (GLP-1), oxyntomodulin and cholecystokinin before start during standard mixed-meal test (cfr.supra)

  9. change in fasting adipokine levels

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

    Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6)

  10. change in fasting lipid levels

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

    Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol

Other outcomes

  1. Resting energy expenditure

    Time frame: At enrollment in group 1-4

    Resting energy expenditure determined using indirect calorimetry

  2. Weight

    Time frame: At enrollment in group 1-4

  3. Standing height

    Time frame: At enrollment in group 1-4

  4. Waist and hip circumference

    Time frame: At enrollment in group 1-4

  5. Change in resting energy expenditure

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

    Resting energy expenditure determined using indirect calorimetry

  6. Weight change

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

  7. Change in standing height

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

  8. Change in waist and hip circumference

    Time frame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5

Sponsors and collaborators

Lead sponsor

University Hospital, Ghent

Other

Collaborators

  • Pfizer

Registry information

Important dates

Study start
2014
Primary completion
2017
Study completion
2017
First posted
Jun 2, 2014
Registry last updated
Dec 29, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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