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

June 20, 2008 updated by: Federico II University

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Actual)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Naples, Italy, 80131
        • Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Group A
>15 patients treated only with SSA (octreotide-LAR or lanreotide depot)
Drug: 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
Other Names:
  • Sandostatin-LAR (Novartis), Ipstyl (Ipsen)
Group B
>15 patients treated with surgery after a period of SSA treatment of 6-24 months
Drug: 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
Other Names:
  • Sandostatin-LAR (Novartis), Ipstyl (Ipsen)
Procedure: Transsphenoidal adenomectomy
Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.
Group C
>15 patients cured after surgery only
Procedure: Transsphenoidal adenomectomy
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
Drug: 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
Other Names:
  • Sandostatin-LAR (Novartis), Ipstyl (Ipsen)
Procedure: Transsphenoidal adenomectomy
Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes of fasting glucose levels.
Time Frame: 0, 6-12 and 60 months
0, 6-12 and 60 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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
0, 6-12, 60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federico II University

Investigators

  • Principal Investigator: Annamaria Colao, MD, Federico II University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 1997

Primary Completion (Actual)

June 1, 2008

Study Completion (Actual)

June 1, 2008

Study Registration Dates

First Submitted

June 20, 2008

First Submitted That Met QC Criteria

June 20, 2008

First Posted (Estimate)

June 23, 2008

Study Record Updates

Last Update Posted (Estimate)

June 23, 2008

Last Update Submitted That Met QC Criteria

June 20, 2008

Last Verified

June 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NeuroendoUnit-10

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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