Cardiovascular Outcome After Surgery or Somatostatin Analogues

NCT00615004 | Completed

• 1 other identifier: NeuroendoUnit-7
• Study Type: observational
• Target: 215
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acromegaly

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (1)

• Changes in the total/HDL cholesterol ratio, glucose tolerance, measured as fasting glucose levels and HOMA reduction, and improvement of pituitary function

  12 months

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

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

Naples, Naples, 80131, Italy

Location

Related Publications (12)

• Colao A, Lombardi G. Growth-hormone and prolactin excess. Lancet. 1998 Oct 31;352(9138):1455-61. doi: 10.1016/S0140-6736(98)03356-X.

  PMID: 9808008 RESULT

• Melmed S. Medical progress: Acromegaly. N Engl J Med. 2006 Dec 14;355(24):2558-73. doi: 10.1056/NEJMra062453. No abstract available.

  PMID: 17167139 RESULT

• Melmed S, Casanueva F, Cavagnini F, Chanson P, Frohman LA, Gaillard R, Ghigo E, Ho K, Jaquet P, Kleinberg D, Lamberts S, Laws E, Lombardi G, Sheppard MC, Thorner M, Vance ML, Wass JA, Giustina A. Consensus statement: medical management of acromegaly. Eur J Endocrinol. 2005 Dec;153(6):737-40. doi: 10.1530/eje.1.02036.

  PMID: 16322377 RESULT

• Sheppard MC. Primary medical therapy for acromegaly. Clin Endocrinol (Oxf). 2003 Apr;58(4):387-99. doi: 10.1046/j.1365-2265.2003.01734.x.

  PMID: 12641619 RESULT

• Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S. Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab. 2000 Feb;85(2):526-9. doi: 10.1210/jcem.85.2.6363.

  PMID: 10690849 RESULT

• 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.

  PMID: 17259801 RESULT

• Cappabianca P, Alfieri A, Colao A, Ferone D, Lombardi G, de Divitiis E. Endoscopic endonasal transsphenoidal approach: an additional reason in support of surgery in the management of pituitary lesions. Skull Base Surg. 1999;9(2):109-17. doi: 10.1055/s-2008-1058157.

  PMID: 17171126 RESULT

• Galderisi M, Vitale G, Bianco A, Pivonello R, Lombardi G, Divitiis Od, Colao A. Pulsed tissue Doppler identifies subclinical myocardial biventricular dysfunction in active acromegaly. Clin Endocrinol (Oxf). 2006 Apr;64(4):390-7. doi: 10.1111/j.1365-2265.2006.02475.x.

  PMID: 16584510 RESULT

• Colao A, Pivonello R, Rosato F, Tita P, De Menis E, Barreca A, Ferrara R, Mainini F, Arosio M, Lombardi G. First-line octreotide-LAR therapy induces tumour shrinkage and controls hormone excess in patients with acromegaly: results from an open, prospective, multicentre trial. Clin Endocrinol (Oxf). 2006 Mar;64(3):342-51. doi: 10.1111/j.1365-2265.2006.02467.x.

  PMID: 16487447 RESULT

• 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.

  PMID: 14769829 RESULT

• Colao A, Auriemma RS, Savastano S, Galdiero M, Grasso LF, Lombardi G, Pivonello R. Glucose tolerance and somatostatin analog treatment in acromegaly: a 12-month study. J Clin Endocrinol Metab. 2009 Aug;94(8):2907-14. doi: 10.1210/jc.2008-2627. Epub 2009 Jun 2.

  PMID: 19491229 DERIVED

• 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.

  PMID: 18445662 DERIVED

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.

MeSH Terms

Conditions

Acromegaly

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Annamaria Colao, MD

  Federico II University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 1, 2008
• First Posted: February 14, 2008
• Study Start: January 1, 1997
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: February 14, 2008

Record last verified: 2007-12

Locations

IT (1)