Cardiovascular Outcome After Surgery or Somatostatin Analogues (CVAcro)

This study has been completed.
Sponsor:
Information provided by:
Federico II University
ClinicalTrials.gov Identifier:
NCT00615004
First received: February 1, 2008
Last updated: February 13, 2008
Last verified: December 2007
  Purpose

A direct comparison between the results of surgery or somatostatin analogues (SSA) on cardiovascular complication in acromegaly has never been performed.

Our objective is to investigate whether first-line surgery or SSA have a different outcome on cardiomyopathy after 12 months. The design of the study is retrospective, comparative, non randomized, because of ethical problems.

Setting University Hospital. All patients treated with SSA [either octreotide-LAR (10-40 mg/q28d), or lanreotide (30-120 mg/q28d); dosages up-titrated to control GH and IGF-I levels] or operated on by transsphenoidal approach. For the purposes of this study only controlled patients will be included.

Measurements Primary outcome measures were changes in left ventricular mass index (LVMi), diastolic [early to atrial mitral flow velocity (E/A)] and systolic perform-ance [LV ejection fraction (LVEF)]. Secondary outcome measures were reduction of total/HDL-cholesterol ratio, as a cardiovascular (CV) risk parameter, improvement of glucose profile and pituitary function, as indirect causes of CV improvement.

Expected results: SSA and surgery groups should have similar results in terms of improvement of cardiomyopathy. However, recent data suggest that SSA reduce directly heart rate and cardiomyocytes performance: clinical implications of these evidences suggest that SSA will improve cardiovascular outcome more than surgery. Moreover, after surgery, replacement therapy already stabilised or of new onset, has never been considered so far in this setting.


Condition
Acromegaly

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: An Observational, Retrospective, Comparative Study to Investigate Differential Outcome on Cardiomyopathy Following Control of Acromegaly After Surgery or Somatostatin Analogues Given as First-Line Therapy

Resource links provided by NLM:


Further study details as provided by Federico II University:

Primary Outcome Measures:
  • Changes of left ventricular mass index (LVMi), as measure of LV hypertrophy, early to atrial mitral flow velocity (E/A), as measure of diastolic function, and left ventricular ejection fraction (LVEF), as measure of systolic function. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in the total/HDL cholesterol ratio, glucose tolerance, measured as fasting glucose levels and HOMA reduction, and improvement of pituitary function [ Time Frame: 12 months ] [ Designated as safety issue: No ]

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: 215
Study Start Date: January 1997
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Groups/Cohorts
1-SSA
All patients receiving first-line depot SSA treatment, with either octreotide-LAR or lanreotide, achieving control of the disease, and with available follow-up after 12 months of treatment.
2-Surgery
All patients treated with first-line surgery via trans-sphenoidal route by microscopic and/or endoscopic approach, who did not require any additional therapy for acromegaly and with available follow-up after 12 months of treatment

Detailed Description:

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 December 31st 2006, 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 12 months. Due to the study design, this is a non randomized 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.

Cure criteria are considered according with Giustina et al. Acromegaly is considered to be controlled if mean fasting GH levels were ≤2.5 μg/liter in presence of normal IGF-I levels for sex and age. Nadir GH after oral glucose load (oGTT) ≤1 μg/liter is also an option to evaluate disease control according with the 2000 Consensus Statement. However, oGTT is generally not routinely performed in patients receiving SSA, since GH-induced glucose suppression is likely to be mediated by the endogenous somatostatin tone. To avoid ascertainment bias, disease control after surgery and SSA will be only based on fasting GH and IGF-I levels. The diagnosis of acromegaly is defined as previously reported, by high serum GH levels during a 6 hr time course, not suppressible <1 µg/l after oGTT and high plasma IGF-I levels for age [expressed as value upper limit of normal range (ULN)].

For the purpose of this study only the patients with controlled acromegaly will be included to provide a period of follow-up long enough to investigate changes in cardiomyopathy parameters.

Study protocol: As for our routine procedure, at diagnosis all the patients undergo a complete metabolic and endocrine screening. After an overnight fasting, serum IGF-I levels are assayed twice in a single sample at the time 0 of the GH profile; GH levels are calculated as the mean value of at least 5 (up to 8) samples drawn every 30 min over a period of three-six hours and the average value will be considered for the statistical analysis; fasting total cholesterol, HDL cholesterol, glucose and insulin levels are also measured. The total/HDL-cholesterol ratio, index of cardiovascular risk, is calculated.

  Eligibility

Ages Eligible for Study:   18 Years to 85 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 December 31st 2006, 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 12 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 first-line surgery via trans-sphenoidal route by microscopic and/or endoscopic approach or with first-line depot SSA treatment
  • Achieving control of the disease; AND
  • With available follow-up after 12 months of treatment

Exclusion Criteria:

  • Patients receiving second surgery within 3 months from first surgery
  • Requiring combined dopamine-agonists and SSA because of a mixed GH/PRL-secreting tumor
  • Receiving the s.c. octreotide for longer than 15 days; OR
  • Requiring surgery or SSA as second-line treatment before the completion of the 12 months or with a follow-up shorter than 6 months after surgery or pharmacotherapy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00615004

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: NCT00615004     History of Changes
Other Study ID Numbers: NeuroendoUnit-7
Study First Received: February 1, 2008
Last Updated: February 13, 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
Somatostatin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 14, 2014