AcromegalyNCT02152124
Growth Hormone, IGF-1 and Medical Treatment in Acromegaly: Are There Effects on Gut Hormone Physiology and Postprandial Substrate Metabolism?
An observational study of Acromegaly, run by University Hospital, Ghent at 1 site in Belgium.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Acromegaly
- How many people
- 21 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Jun 2014to 31 Aug 2017
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Groups 1-3 and 5: outpatient clinic attendants Group 4: recruted from community (by placard)
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Belgium1 site
Ghent University Hospital, Department of Endocrinology, 9K12IE
Ghent, 9000
About this study
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:
Read more
- 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.
- Conditions
- Acromegaly
- Keywords
- Acromegaly, Acromegaly treatment, Long-acting somatostatin analogs, Pegvisomant, Insulin sensitivity, Gut hormones, Lipid metabolism, Adipokines
- Medical subject headings
- Acromegaly, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in insulin sensitivity
Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM)
Measured: before start of pegvisomant and 3 months after normalisation of IGF-1 after start of pegvisomant in group 5
insulin sensitivity
Glucose disposal rate during last half hour of hyperinsulinemic-euglycemic clamp procedure, corrected for lean body mass (in µmol/min/kgLBM)
Measured: At enrollment in groups 1-4
Secondary outcomes (10)
fasting and postprandial glucose
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)
Measured: At enrollment in groups 1-4
fasting and postprandial insulin
Insulin levels during standard mixed-meal test (cfr.supra)
Measured: At enrollment in groups 1-4
fasting and postprandial gut hormone levels
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)
Measured: At enrollment in groups 1-4
fasting adipokine levels
Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6)
Measured: At enrollment in group 1-4
fasting lipid levels
Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol
Measured: At enrollment in groups 1-4
change in fasting and postprandial glucose
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)
Measured: 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
Insulin levels during standard mixed-meal test (cfr.supra)
Measured: 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 gut hormone levels
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)
Measured: 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
Fasting serum levels of leptin, adiponectin and interleukin 6 (IL-6)
Measured: 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
Fasting serum levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol
Measured: before start of pegvisomant and 3 months after normalisation of IGF-1 levels after start of pegvisomant in group 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study start1 Jun 2014
- Primary completion31 Aug 2017
- Study completion31 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for AcromegalyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Guy T'Sjoen, MD, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02152124
- Sponsor's protocol ID
- EC/2013/857
- Other IDs
- WI182140
- Status last verified
- Dec 2022
- First submitted
- 21 May 2014
- Last updated
- 29 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
Baldelli R, Battista C, Leonetti F, Ghiggi MR, Ribaudo MC, Paoloni A, D'Amico E, Ferretti E, Baratta R, Liuzzi A, Trischitta V, Tamburrano G. Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment. Clin Endocrinol (Oxf). 2003 Oct;59(4):492-9. doi: 10.1046/j.1365-2265.2003.01876.x.
PubMed 14510913Barkan AL, Burman P, Clemmons DR, Drake WM, Gagel RF, Harris PE, Trainer PJ, van der Lely AJ, Vance ML. Glucose homeostasis and safety in patients with acromegaly converted from long-acting octreotide to pegvisomant. J Clin Endocrinol Metab. 2005 Oct;90(10):5684-91. doi: 10.1210/jc.2005-0331. Epub 2005 Aug 2.
PubMed 16076947Berg C, Petersenn S, Lahner H, Herrmann BL, Buchfelder M, Droste M, Stalla GK, Strasburger CJ, Roggenbuck U, Lehmann N, Moebus S, Jockel KH, Mohlenkamp S, Erbel R, Saller B, Mann K; Investigative Group of the Heinz Nixdorf Recall Study and the German Pegvisomant Observational Study Board and Investigators. Cardiovascular risk factors in patients with uncontrolled and long-term acromegaly: comparison with matched data from the general population and the effect of disease control. J Clin Endocrinol Metab. 2010 Aug;95(8):3648-56. doi: 10.1210/jc.2009-2570. Epub 2010 May 12.
PubMed 20463098Colao A, Pivonello R, Auriemma RS, De Martino MC, Bidlingmaier M, Briganti F, Tortora F, Burman P, Kourides IA, Strasburger CJ, Lombardi G. Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance. Eur J Endocrinol. 2006 Mar;154(3):467-77. doi: 10.1530/eje.1.02112.
PubMed 16498061De Marinis L, Bianchi A, Fusco A, Cimino V, Mormando M, Tilaro L, Mazziotti G, Pontecorvi A, Giustina A. Long-term effects of the combination of pegvisomant with somatostatin analogs (SSA) on glucose homeostasis in non-diabetic patients with active acromegaly partially resistant to SSA. Pituitary. 2007;10(3):227-32. doi: 10.1007/s11102-007-0037-7.
PubMed 17484056Freda PU, Reyes CM, Conwell IM, Sundeen RE, Wardlaw SL. Serum ghrelin levels in acromegaly: effects of surgical and long-acting octreotide therapy. J Clin Endocrinol Metab. 2003 May;88(5):2037-44. doi: 10.1210/jc.2002-021683.
PubMed 12727951Kim SK, Suh S, Lee JI, Hur KY, Chung JH, Lee MK, Min YK, Kim JH, Kim JH, Kim KW. The ability of beta-cells to compensate for insulin resistance is restored with a reduction in excess growth hormone in Korean acromegalic patients. J Korean Med Sci. 2012 Feb;27(2):177-83. doi: 10.3346/jkms.2012.27.2.177. Epub 2012 Jan 27.
PubMed 22323865Kozakowski J, Rabijewski M, Zgliczynski W. [Lowered ghrelin levels in acromegaly-normalization after treatment]. Endokrynol Pol. 2005 Nov-Dec;56(6):862-70. Polish.
PubMed 16821203Mazziotti G, Floriani I, Bonadonna S, Torri V, Chanson P, Giustina A. Effects of somatostatin analogs on glucose homeostasis: a metaanalysis of acromegaly studies. J Clin Endocrinol Metab. 2009 May;94(5):1500-8. doi: 10.1210/jc.2008-2332. Epub 2009 Feb 10.
PubMed 19208728Moller N, Jorgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009 Apr;30(2):152-77. doi: 10.1210/er.2008-0027. Epub 2009 Feb 24.
PubMed 19240267Moller L, Norrelund H, Jessen N, Flyvbjerg A, Pedersen SB, Gaylinn BD, Liu J, Thorner MO, Moller N, Lunde Jorgensen JO. Impact of growth hormone receptor blockade on substrate metabolism during fasting in healthy subjects. J Clin Endocrinol Metab. 2009 Nov;94(11):4524-32. doi: 10.1210/jc.2009-0381. Epub 2009 Oct 9.
PubMed 19820031Neggers SJ, Kopchick JJ, Jorgensen JO, van der Lely AJ. Hypothesis: Extra-hepatic acromegaly: a new paradigm? Eur J Endocrinol. 2011 Jan;164(1):11-6. doi: 10.1530/EJE-10-0969. Epub 2010 Nov 2.
PubMed 21045065Peracchi M, Porretti S, Gebbia C, Pagliari C, Bucciarelli P, Epaminonda P, Manenti S, Arosio M. Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly. Eur J Endocrinol. 2001 Jul;145(1):R1-4. doi: 10.1530/eje.0.145r001.
PubMed 11415859Pierluissi J, de Pierluissi RM. Effect of glucose-dependent insulinotropic polypeptide (GIP) on insulin response to glucose in acromegalics. Acta Cient Venez. 1995;46(2):89-96.
PubMed 9279024Plockinger U, Holst JJ, Messerschmidt D, Hopfenmuller W, Quabbe HJ. Octreotide suppresses the incretin glucagon-like peptide (7-36) amide in patients with acromegaly or clinically nonfunctioning pituitary tumors and in healthy subjects. Eur J Endocrinol. 1999 Jun;140(6):538-44. doi: 10.1530/eje.0.1400538.
PubMed 10377503