Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly

NCT ID: NCT00703079

Last Updated: 2008-06-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1997-01-31
• Study Completion Date: 2008-06-30

Brief 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 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.

Conditions

Acromegaly

Keywords

Acromegaly; GH; IGF-I; Octreotide-LAR; Lanreotide; Transsphenoidal surgery

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group A

\>15 patients treated only with SSA (octreotide-LAR or lanreotide depot)

Octreotide-LAR or lanreotide

Intervention Type: DRUG

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

Group B

\>15 patients treated with surgery after a period of SSA treatment of 6-24 months

Octreotide-LAR or lanreotide

Intervention Type: DRUG

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 adenomectomy

Intervention Type: PROCEDURE

Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.

Group C

\>15 patients cured after surgery only

Transsphenoidal adenomectomy

Intervention Type: PROCEDURE

Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.

Group D

\>15 patients treated with surgery first and then with SSA after 6-12 months

Octreotide-LAR or lanreotide

Intervention Type: DRUG

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 adenomectomy

Intervention Type: PROCEDURE

Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.

Interventions

Octreotide-LAR or lanreotide

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

Intervention Type: DRUG

Transsphenoidal adenomectomy

Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.

Intervention Type: PROCEDURE

Other Intervention Names

Sandostatin-LAR (Novartis), Ipstyl (Ipsen)

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: lead

Responsible Party

Department of Molecular and Clinical Endocrinology and Oncology

Principal Investigators

Annamaria Colao, MD

Role: PRINCIPAL_INVESTIGATOR

Federico II University

Locations

Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples

Naples, , Italy

Countries

Italy

References

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.

Reference Type: RESULT

PMID: 14769829 (View on PubMed)

Pereira 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.

Reference Type: RESULT

PMID: 15649100 (View on PubMed)

Kasayama 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.

Reference Type: RESULT

PMID: 10792333 (View on PubMed)

Lamberts 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.

Reference Type: RESULT

PMID: 2866445 (View on PubMed)

Colao 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.

Reference Type: RESULT

PMID: 18445662 (View on PubMed)

Colao 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.

Reference Type: RESULT

PMID: 17984237 (View on PubMed)

Colao 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.

Reference Type: RESULT

PMID: 17259801 (View on PubMed)

Colao 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.

Reference Type: DERIVED

PMID: 19001517 (View on PubMed)

Other Identifiers

NeuroendoUnit-10

Identifier Type: -

Identifier Source: org_study_id