Clinical trial NCT02152124: Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?
Official title: Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acromegaly
Keywords: Acromegaly
Acromegaly treatment
Long-acting somatostatin analogs
Pegvisomant
Insulin sensitivity
Gut hormones
Lipid metabolism
Adipokines
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2014-06-02
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Groups 1-3 and 5: outpatient clinic attendants Group 4: recruted from community (by placard)

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.


Eligibility 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

Primary outcomes:
measure: change in insulin sensitivity
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 after start of pegvisomant in group 5
measure: insulin sensitivity
timeFrame: At enrollment in groups 1-4
Secondary outcomes:
measure: fasting and postprandial glucose
timeFrame: At enrollment in groups 1-4
measure: fasting and postprandial insulin
timeFrame: At enrollment in groups 1-4
measure: fasting and postprandial gut hormone levels
timeFrame: At enrollment in groups 1-4
measure: fasting adipokine levels
timeFrame: At enrollment in group 1-4
measure: fasting lipid levels
timeFrame: At enrollment in groups 1-4
measure: change in fasting and postprandial glucose
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
measure: change in fasting and postprandial insulin levels
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
measure: change in fasting and postprandial gut hormone levels
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
measure: change in fasting adipokine levels
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
measure: change in fasting lipid levels
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
Other outcomes:
measure: Resting energy expenditure
timeFrame: At enrollment in group 1-4
measure: Weight
timeFrame: At enrollment in group 1-4
measure: Standing height
timeFrame: At enrollment in group 1-4
measure: Waist and hip circumference
timeFrame: At enrollment in group 1-4
measure: Change in resting energy expenditure
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
measure: Weight change
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
measure: Change in standing height
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
measure: Change in waist and hip circumference
timeFrame: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital, Department of Endocrinology, 9K12IE
Study officials:
affiliation: University Hospital, Ghent
name: Guy T'Sjoen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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