AcromegalyGLUSSANCT00703079
Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly
An observational study of Acromegaly, run by Federico II University at 1 site in Italy.
Trial summary
To investigate the 60 month impact of surgery and somatostatin analogues (SSA) on glucose metabolism in acromegaly we will analyzed data from 100 patients with acromegaly according with different treatments (group A=with SSA only; group B= SSA followed by surgery; group C= surgery only; group D= surgery followed by… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acromegaly
- What is being tested?
- Octreotide-LAR or lanreotide and Transsphenoidal adenomectomy
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- Jan 1997to Jun 2008
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- No healthy volunteers
- Adult, Older adult
Study population: We will review all files from consecutive patients with active acromegaly coming to the Units of Endocrinology or Neurosurgery of the "Federico II" University of Naples from Jan 1st 1997 to June 1st 2008, primarily treated with either surgery or depot SSA, i.e. lanreotide (LAN) or slow-release octreotide (LAR), and with an available follow-up of at least 60 months. Due to the study design, this is a non ran-domized study. However, our routine procedure generally considers first-line treatment with SSA for 6-12 months, unless the tumors are clearly non invasive on Magnetic Resonance Imaging (MRI) and/or the patients who do not present any surgical or anesthesiological risk.
Who may be able to join
- Patients treated with either first-line surgery via trans-sphenoidal route by microscopic and/or endoscopic approach or with first-line depot SSA treatment, or both and
- Patients with available follow-up after 60 months of treatment
Who cannot join
- Patients requiring dopamine-agonists or pegvisomant
- Patients receiving the s.c. octreotide for longer than 15 days
- Patients receiving radiotherapy,
- Patients with a follow-up shorter than 60 months
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples
Naples, 80131
About this study
Official title: Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly: Results of a 5 Years Observational, Open, Prospective Study
To investigate the 60 month impact of surgery and somatostatin analogues (SSA) on glucose metabolism in acromegaly we will analyzed data from 100 patients with acromegaly according with different treatments (group A=with SSA only; group B= SSA followed by surgery; group C= surgery only; group D= surgery followed by SSA). At diagnosis and after 6-12 and 60 months were analyzed as primary outcome measure changes in fasting glucose and as secondary outcome measures changes of glycated hemoglobin (HbA1c) and insulin levels, HOMA-R and HOMA-β, representing insulin resistance and β-cell function, respectively.
We will enrol 100 patients and expect half of them to have IGT or diabetes mellitus. We do not expect changes according with different treatment after 60 months while SSA-treated patients might experience deterioration of glucose tolerance after 6-12 months. We intend to look for predictors of deterioration of glucose tolerance.
Read the detailed description
Impaired glucose tolerance (IGT) and overt diabetes mellitus are frequently associated with acromegaly. Patients with acromegaly are insulin resistant both in the liver and in the periphery, displaying hyperinsulinemia and increased glucose turn-over in the basal post-absorptive states. The prevalence of diabetes mellitus and that of IGT in acromegaly is unknown but is reported to range 19-56% and 16-46% in different series. The increased cardiovascular morbidity and mortality associated with acromegaly may party be a consequence of the increased insulin resistance that frequently accompanies GH excess. Glucose tolerance may worsen in patients treated with somatostatin analogues (SSA), because insulin secretion, i.e. β-cell function, is also suppressed. SSA induce control of GH and IGF-I excess in approximately 60% of patients after 12 months of treatment with no significant difference as applied after unsuccessful surgery or as first-line in newly diagnosed patients and control of GH and IGF-I levels occur with an even higher prevalence after a longer period of treatment. The inhibitory effect of SSA on pancreatic insulin secretion might, however, complicate the overall effect of this treatment on glucose tolerance. We recently demonstrated that 12 months after first-line treatment with SSA or surgery produced a similar improvement in LV hypertrophy and diastolic filling while systolic function increased more evidently in SSA-treated patients, total/HDL-cholesterol ratio significantly reduced only in SSA-treated patients while fasting glucose levels significantly reduced only in surgery-treated patients. A normal pituitary function was found in 46.4% of SSA-treated and in 36.4% of surgery-treated patients, resulting unchanged in the former and slightly reduced in the latter. Both a direct effect of SSA and a more preserved pituitary function might explain these results. Longitudinal data of glucose tolerance in patients with acromegaly and with or without diabetes treated long-term with SSA or surgery or both are still very limited.
In order to investigate whether SSA negatively impact glucose tolerance in acromegaly, we will analyze data collected prospectively during a 10 year period. We will compare the results of glucose tolerance at diagnosis after 6-12 months and after 60 months of treatment with SSA or surgery. Patients will be grouped according with their treatment (SSA only, surgery only, SSA followed by surgery and SSA followed by surgery and SSA) in order to establish the effects on glucose tolerance mediated by disease control and type of treatment.
- Conditions
- Acromegaly
- Being tested
- Octreotide-LAR or lanreotide, Transsphenoidal adenomectomy
- Keywords
- Acromegaly, GH, IGF-I, Octreotide-LAR, Lanreotide, Transsphenoidal surgery
- Medical subject headings
- Acromegaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Octreotide-LAR or lanreotideDrug
Also called Sandostatin-LAR (Novartis), Ipstyl (Ipsen)
Treated with octreotide-LAR will be given at dosages of 10-40 mg/q28d and treatment with lanreotide-SR at dosages of 60-120 mg/q28d. The dosages are up-titrated to control GH and IGF-I levels
Transsphenoidal adenomectomyProcedure or surgery
Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.
| Study group | Role | What they receive |
|---|---|---|
| Group A | >15 patients treated only with SSA (octreotide-LAR or lanreotide depot) Receives: Drug: Octreotide-LAR or lanreotide | |
| Group B | >15 patients treated with surgery after a period of SSA treatment of 6-24 months Receives: Drug: Octreotide-LAR or lanreotide; Procedure: Transsphenoidal adenomectomy | |
| Group C | >15 patients cured after surgery only Receives: Procedure: Transsphenoidal adenomectomy | |
| Group D | >15 patients treated with surgery first and then with SSA after 6-12 months Receives: Drug: Octreotide-LAR or lanreotide; Procedure: Transsphenoidal adenomectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of fasting glucose levels.
Measured: 0, 6-12 and 60 months
Secondary outcomes (1)
changes in Hb1Ac levels changes in fasting insulin levels changes in HOMA-R index changes in HOMA-β index
Measured: 0, 6-12, 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2008 (estimated)
- Study startJan 1997
- Primary completionJun 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for AcromegalyStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Investigators
- Annamaria Colao, MD, Principal investigator, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00703079
- Sponsor's protocol ID
- NeuroendoUnit-10
- Acronym
- GLUSSA
- Status last verified
- Jun 2008
- First submitted
- 20 Jun 2008
- Last updated
- 23 Jun 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004 Feb;25(1):102-52. doi: 10.1210/er.2002-0022.
PubMed 14769829Pereira AM, Biermasz NR, Roelfsema F, Romijn JA. Pharmacologic therapies for acromegaly: a review of their effects on glucose metabolism and insulin resistance. Treat Endocrinol. 2005;4(1):43-53. doi: 10.2165/00024677-200504010-00005.
PubMed 15649100Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, Koga M, Saitoh Y, Ohnishi T, Arita N. Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrinol (Oxf). 2000 May;52(5):549-55. doi: 10.1046/j.1365-2265.2000.00986.x.
PubMed 10792333Lamberts SW, Uitterlinden P, Verschoor L, van Dongen KJ, del Pozo E. Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995. N Engl J Med. 1985 Dec 19;313(25):1576-80. doi: 10.1056/NEJM198512193132504.
PubMed 2866445Colao A, Pivonello R, Galderisi M, Cappabianca P, Auriemma RS, Galdiero M, Cavallo LM, Esposito F, Lombardi G. Impact of treating acromegaly first with surgery or somatostatin analogs on cardiomyopathy. J Clin Endocrinol Metab. 2008 Jul;93(7):2639-46. doi: 10.1210/jc.2008-0299. Epub 2008 Apr 29.
PubMed 18445662Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Lombardi G. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007 Nov;157(5):579-87. doi: 10.1530/EJE-07-0383.
PubMed 17984237Colao A, Martino E, Cappabianca P, Cozzi R, Scanarini M, Ghigo E; A.L.I.C.E. Study Group. First-line therapy of acromegaly: a statement of the A.L.I.C.E. (Acromegaly primary medical treatment Learning and Improvement with Continuous Medical Education) Study Group. J Endocrinol Invest. 2006 Dec;29(11):1017-20. doi: 10.1007/BF03349217. No abstract available.
PubMed 17259801Colao A, Auriemma RS, Galdiero M, Cappabianca P, Cavallo LM, Esposito F, Grasso LF, Lombardi G, Pivonello R. Impact of somatostatin analogs versus surgery on glucose metabolism in acromegaly: results of a 5-year observational, open, prospective study. J Clin Endocrinol Metab. 2009 Feb;94(2):528-37. doi: 10.1210/jc.2008-1546. Epub 2008 Nov 11.
PubMed 19001517
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly: Results of a 5 Years Observational, Open, Prospective Study
- ClinicalTrials.gov ID
- NCT00703079
- Acronym / sponsor ID
- GLUSSA / NeuroendoUnit-10
- Conditions
- Acromegaly
- Keywords
- Acromegaly, GH, IGF-I, Octreotide-LAR, Lanreotide, Transsphenoidal surgery
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- Jan 1997
- Primary completion
- Jun 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 23 Jun 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate the 60 month impact of surgery and somatostatin analogues (SSA) on glucose metabolism in acromegaly we will analyzed data from 100 patients with acromegaly according with different treatments (group A=with SSA only; group B= SSA followed by surgery; group C= surgery only; group D= surgery followed by SSA). At diagnosis and after 6-12 and 60 months were analyzed as primary outcome measure changes in fasting glucose and as secondary outcome measures changes of glycated hemoglobin (HbA1c) and insulin levels, HOMA-R and HOMA-β, representing insulin resistance and β-cell function, respectively.
We will enrol 100 patients and expect half of them to have IGT or diabetes mellitus. We do not expect changes according with different treatment after 60 months while SSA-treated patients might experience deterioration of glucose tolerance after 6-12 months. We intend to look for predictors of deterioration of glucose tolerance.
Detailed description
Impaired glucose tolerance (IGT) and overt diabetes mellitus are frequently associated with acromegaly. Patients with acromegaly are insulin resistant both in the liver and in the periphery, displaying hyperinsulinemia and increased glucose turn-over in the basal post-absorptive states. The prevalence of diabetes mellitus and that of IGT in acromegaly is unknown but is reported to range 19-56% and 16-46% in different series. The increased cardiovascular morbidity and mortality associated with acromegaly may party be a consequence of the increased insulin resistance that frequently accompanies GH excess. Glucose tolerance may worsen in patients treated with somatostatin analogues (SSA), because insulin secretion, i.e. β-cell function, is also suppressed. SSA induce control of GH and IGF-I excess in approximately 60% of patients after 12 months of treatment with no significant difference as applied after unsuccessful surgery or as first-line in newly diagnosed patients and control of GH and IGF-I levels occur with an even higher prevalence after a longer period of treatment. The inhibitory effect of SSA on pancreatic insulin secretion might, however, complicate the overall effect of this treatment on glucose tolerance. We recently demonstrated that 12 months after first-line treatment with SSA or surgery produced a similar improvement in LV hypertrophy and diastolic filling while systolic function increased more evidently in SSA-treated patients, total/HDL-cholesterol ratio significantly reduced only in SSA-treated patients while fasting glucose levels significantly reduced only in surgery-treated patients. A normal pituitary function was found in 46.4% of SSA-treated and in 36.4% of surgery-treated patients, resulting unchanged in the former and slightly reduced in the latter. Both a direct effect of SSA and a more preserved pituitary function might explain these results. Longitudinal data of glucose tolerance in patients with acromegaly and with or without diabetes treated long-term with SSA or surgery or both are still very limited.
In order to investigate whether SSA negatively impact glucose tolerance in acromegaly, we will analyze data collected prospectively during a 10 year period. We will compare the results of glucose tolerance at diagnosis after 6-12 months and after 60 months of treatment with SSA or surgery. Patients will be grouped according with their treatment (SSA only, surgery only, SSA followed by surgery and SSA followed by surgery and SSA) in order to establish the effects on glucose tolerance mediated by disease control and type of treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A | – | Drug: Octreotide-LAR or lanreotide>15 patients treated only with SSA (octreotide-LAR or lanreotide depot) |
| Group B | – | Drug: Octreotide-LAR or lanreotide, Procedure: Transsphenoidal adenomectomy>15 patients treated with surgery after a period of SSA treatment of 6-24 months |
| Group C | – | Procedure: Transsphenoidal adenomectomy>15 patients cured after surgery only |
| Group D | – | Drug: Octreotide-LAR or lanreotide, Procedure: Transsphenoidal adenomectomy>15 patients treated with surgery first and then with SSA after 6-12 months |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- We will review all files from consecutive patients with active acromegaly coming to the Units of Endocrinology or Neurosurgery of the "Federico II" University of Naples from Jan 1st 1997 to June 1st 2008, primarily treated with either surgery or depot SSA, i.e. lanreotide (LAN) or slow-release octreotide (LAR), and with an available follow-up of at least 60 months. Due to the study design, this is a non ran-domized study. However, our routine procedure generally considers first-line treatment with SSA for 6-12 months, unless the tumors are clearly non invasive on Magnetic Resonance Imaging (MRI) and/or the patients who do not present any surgical or anesthesiological risk.
Key inclusion criteria (2 listed)
- Patients treated with either first-line surgery via trans-sphenoidal route by microscopic and/or endoscopic approach or with first-line depot SSA treatment, or both and
- Patients with available follow-up after 60 months of treatment
Key exclusion criteria (4 listed)
- Patients requiring dopamine-agonists or pegvisomant
- Patients receiving the s.c. octreotide for longer than 15 days
- Patients receiving radiotherapy,
- Patients with a follow-up shorter than 60 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Octreotide-LAR or lanreotideAlso: Sandostatin-LAR (Novartis), Ipstyl (Ipsen)Treated with octreotide-LAR will be given at dosages of 10-40 mg/q28d and treatment with lanreotide-SR at dosages of 60-120 mg/q28d. The dosages are up-titrated to control GH and IGF-I levels | Drug | Group A, Group B, Group D |
| Transsphenoidal adenomectomyRemoval of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted. | Procedure or surgery | Group B, Group C, Group D |
Primary outcome
Changes of fasting glucose levels.
Time frame: 0, 6-12 and 60 months
1 secondary outcome
changes in Hb1Ac levels changes in fasting insulin levels changes in HOMA-R index changes in HOMA-β index
Time frame: 0, 6-12, 60 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2008.
- Results publication: PubMed 14769829Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004 Feb;25(1):102-52. doi: 10.1210/er.2002-0022.
- Results publication: PubMed 15649100Pereira AM, Biermasz NR, Roelfsema F, Romijn JA. Pharmacologic therapies for acromegaly: a review of their effects on glucose metabolism and insulin resistance. Treat Endocrinol. 2005;4(1):43-53. doi: 10.2165/00024677-200504010-00005.
- Results publication: PubMed 10792333Kasayama S, Otsuki M, Takagi M, Saito H, Sumitani S, Kouhara H, Koga M, Saitoh Y, Ohnishi T, Arita N. Impaired beta-cell function in the presence of reduced insulin sensitivity determines glucose tolerance status in acromegalic patients. Clin Endocrinol (Oxf). 2000 May;52(5):549-55. doi: 10.1046/j.1365-2265.2000.00986.x.
- Results publication: PubMed 2866445Lamberts SW, Uitterlinden P, Verschoor L, van Dongen KJ, del Pozo E. Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995. N Engl J Med. 1985 Dec 19;313(25):1576-80. doi: 10.1056/NEJM198512193132504.
- Results publication: PubMed 18445662Colao A, Pivonello R, Galderisi M, Cappabianca P, Auriemma RS, Galdiero M, Cavallo LM, Esposito F, Lombardi G. Impact of treating acromegaly first with surgery or somatostatin analogs on cardiomyopathy. J Clin Endocrinol Metab. 2008 Jul;93(7):2639-46. doi: 10.1210/jc.2008-0299. Epub 2008 Apr 29.
- Results publication: PubMed 17984237Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Lombardi G. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007 Nov;157(5):579-87. doi: 10.1530/EJE-07-0383.
- Results publication: PubMed 17259801Colao A, Martino E, Cappabianca P, Cozzi R, Scanarini M, Ghigo E; A.L.I.C.E. Study Group. First-line therapy of acromegaly: a statement of the A.L.I.C.E. (Acromegaly primary medical treatment Learning and Improvement with Continuous Medical Education) Study Group. J Endocrinol Invest. 2006 Dec;29(11):1017-20. doi: 10.1007/BF03349217. No abstract available.
- Derived from this study: PubMed 19001517Colao A, Auriemma RS, Galdiero M, Cappabianca P, Cavallo LM, Esposito F, Grasso LF, Lombardi G, Pivonello R. Impact of somatostatin analogs versus surgery on glucose metabolism in acromegaly: results of a 5-year observational, open, prospective study. J Clin Endocrinol Metab. 2009 Feb;94(2):528-37. doi: 10.1210/jc.2008-1546. Epub 2008 Nov 11.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annamaria Colao, MD principal investigator
Federico II University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acromegaly, run by Federico II University at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of fasting glucose levels. (time frame: 0, 6-12 and 60 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00703079, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2008.