The Importance of Adrenomedullin (AM) on ACTH-Cortisol-Glucose Axis

Hyperglycemia Clinical Trial

— AM  

Official title:

The Importance of Adrenomedullin (AM) on Pituitary-Adrenal Axis and Glucose Kinetics in Pediatric Patients With Systemic Inflammatory Response Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00459511
• Other study ID #: FMUSP/ cappesq 675/05
• Status: Completed
• Phase: Phase 2
• First received: April 11, 2007
• Last updated: April 11, 2007
• Start date: January 2006
• Est. completion date: October 2006

Study information

• Verified date: April 2007
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Observational

Clinical Trial Summary

Hyperglycemia is frequent manifestations of the human metabolic response to systemic inflammatory response syndrome (SIRS),sepsis and septic shock, and are implicated in the clinical outcome.

Adrenomedullin is elevated in SIRS, sepsis and septic shock and has been demonstrated the inhibitory role on insulin and adrenocorticotropic hormone secretion.

Our hypothesis is that: AM elevation after SIRS could be the responsible to maintain hyperglycemia

Description:

Studies in cultured vascular endothelial cells and vascular smooth muscle cells demonstrate that cytokines strongly stimulate adrenomedullin production and release.

Adrenomedullin has been measured in a wide range of clinical researches. Of all conditions investigated, the greatest increment in plasma adrenomedullin has been observed in septic shock. It appears that AM is directly responsible for the hypotension characteristic of septic shock. Studies have shown that administration of AM and AMBP-1 before the onset of sepsis (i.e., pretreatment) prevents transition from the hyperdynamic phase to the hypodynamic phase in the progression of sepsis, attenuates tissue and organ damage, and reduces sepsis-induced mortality.

Two groups described the effects of AM on the pituitary. Taken together, these studies suggest that AM has a role in inhibiting ACTH release.

Mulder et al. first reported the stimulatory effects of adrenomedullin on insulin secretion from isolated rat islets. In direct contrast to this, Martínez et al. clearly demonstrated the inhibitory role of adrenomedullin on insulin secretion in vitro.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 16 Years

Eligibility

Inclusion Criteria:

• Children above 2 years, submitted to elective cardiopulmonary bypass (CPB, only interatrial or ventricular communication) with no endocrine disease or infection.

Exclusion Criteria:

• Children with endocrine disease, undernutrition, with some medication that might interfere in the study (corticosteroids.

Study Design

Observational Model: Defined Population, Primary Purpose: Screening, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Hyperglycemia
• Systemic Inflammatory Response Syndrome

Intervention

Procedure:
• Blood AM, IL-6, ACTH, Cortisol, Glucose and Insulin

Locations

Country	Name	City	State
Brazil	Childrens Institute	Sao Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Country where clinical trial is conducted

Brazil, 

References & Publications (7)

Kapas S, Martínez A, Cuttitta F, Hinson JP. Local production and action of adrenomedullin in the rat adrenal zona glomerulosa. J Endocrinol. 1998 Mar;156(3):477-84. — View Citation

Koo DJ, Zhou M, Chaudry IH, Wang P. The role of adrenomedullin in producing differential hemodynamic responses during sepsis. J Surg Res. 2001 Feb;95(2):207-18. Review. — View Citation

Martínez A, Weaver C, López J, Bhathena SJ, Elsasser TH, Miller MJ, Moody TW, Unsworth EJ, Cuttitta F. Regulation of insulin secretion and blood glucose metabolism by adrenomedullin. Endocrinology. 1996 Jun;137(6):2626-32. — View Citation

Rossi GP, Conconi MT, Malendowicz LK, Nussdorfer GG. Role of the endogenous adrenomedullin system in regulating the secretion and growth of rat adrenal cortex. Hypertens Res. 2003 Feb;26 Suppl:S85-92. — View Citation

Takeuchi M, Morita K, Iwasaki T, Toda Y, Oe K, Taga N, Hirakawa M. Significance of adrenomedullin under cardiopulmonary bypass in children during surgery for congenital heart disease. Acta Med Okayama. 2001 Aug;55(4):245-52. — View Citation

Yoshikawa D, Kawahara F, Okano N, Hiraoka H, Kadoi Y, Fujita N, Morita T, Goto F. Increased plasma concentrations of the mature form of adrenomedullin during cardiac surgery and hepatosplanchnic hypoperfusion. Anesth Analg. 2003 Sep;97(3):663-70. — View Citation

Zhou M, Simms HH, Wang P. Adrenomedullin and adrenomedullin binding protein-1 attenuate vascular endothelial cell apoptosis in sepsis. Ann Surg. 2004 Aug;240(2):321-30. — View Citation