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

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ClinicalTrials.gov Identifier: NCT02152124
Recruitment Status : Enrolling by invitation
First Posted : June 2, 2014
Last Update Posted : December 8, 2016
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University Hospital, Ghent

Brief Summary:

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.


Condition or disease
Acromegaly

Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case Control
Time Perspective: Prospective
Official Title: Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?
Study Start Date : June 2014
Estimated Primary Completion Date : May 2017
Estimated Study Completion Date : August 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Group/Cohort
Controlled on LA-SMSA
Patients with controlled acromegaly on long-acting somatostatin analogs
Controlled on LA-SMSA and pegvisomant
Patients with controlled acromegaly on long-acting somatostatin analogs and pegvisomant
Controlled after surgery
Controlled acromegaly patients without need for medical therapy after surgery
Healhy controls
Healthy volunteers
Uncontrolled on LA-SMSA
Patients with uncontrolled acromegaly (i.e. with serum IGF-1 levels above age-specific thresholds and/or symptoms due to active acromegaly (e.g. excessive sweating, arthralgia)) on LA-SMSA monotherapy in maximal dosage



Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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 ]

Biospecimen Retention:   Samples Without DNA
Serum


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Groups 1-3 and 5: outpatient clinic attendants Group 4: recruted from community (by placard)
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02152124


Locations
Belgium
Ghent University Hospital, Department of Endocrinology, 9K12IE
Ghent, Belgium, 9000
Sponsors and Collaborators
University Hospital, Ghent
Pfizer
Investigators
Principal Investigator: Guy T'Sjoen, MD, PhD University Hospital, Ghent

Publications:

Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT02152124     History of Changes
Other Study ID Numbers: EC/2013/857
WI182140 ( Other Grant/Funding Number: Pfizer )
First Posted: June 2, 2014    Key Record Dates
Last Update Posted: December 8, 2016
Last Verified: December 2016

Keywords provided by University Hospital, Ghent:
Acromegaly
Acromegaly treatment
Long-acting somatostatin analogs
Pegvisomant
Insulin sensitivity
Gut hormones
Lipid metabolism
Adipokines

Additional relevant MeSH terms:
Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Hormones
Somatostatin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs