Trial record 18 of 114 for:    Acromegaly

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

This study has been completed.
Sponsor:
Information provided by:
Federico II University
ClinicalTrials.gov Identifier:
NCT00703079
First received: June 20, 2008
Last updated: NA
Last verified: June 2008
History: No changes posted
  Purpose

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.


Condition Intervention
Acromegaly
Drug: Octreotide-LAR or lanreotide
Procedure: Transsphenoidal adenomectomy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly: Results of a 5 Years Observational, Open, Prospective Study

Resource links provided by NLM:


Further study details as provided by Federico II University:

Primary Outcome Measures:
  • Changes of fasting glucose levels. [ Time Frame: 0, 6-12 and 60 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples Without DNA

Sera from most patients on a yearly bases are stored in our freezed at minus 80° for eventual further studies. No experimental parameters are included in the current study.


Enrollment: 100
Study Start Date: January 1997
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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 Name: 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 Name: 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 Name: Sandostatin-LAR (Novartis), Ipstyl (Ipsen)
Procedure: Transsphenoidal adenomectomy
Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00703079

Locations
Italy
Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples
Naples, Italy, 80131
Sponsors and Collaborators
Federico II University
Investigators
Principal Investigator: Annamaria Colao, MD Federico II University
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Annamaria Colao, Department of Molecular and Clinical Endocrinology and Oncology
ClinicalTrials.gov Identifier: NCT00703079     History of Changes
Other Study ID Numbers: NeuroendoUnit-10
Study First Received: June 20, 2008
Last Updated: June 20, 2008
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency

Keywords provided by Federico II University:
Acromegaly
GH
IGF-I
Octreotide-LAR
Lanreotide
Transsphenoidal surgery

Additional relevant MeSH terms:
Acromegaly
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Octreotide
Lanreotide
Angiopeptin
Somatostatin
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 24, 2014