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

NCT ID: NCT00459511

Last Updated: 2007-04-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

20 participants

Study Classification

OBSERVATIONAL

Study Start Date

2006-01-31

Study Completion Date

2006-10-31

Brief Summary

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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

Detailed Description

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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.

Conditions

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Systemic Inflammatory Response Syndrome Hyperglycemia

Study Design

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Observational Model Type

DEFINED_POPULATION

Study Time Perspective

OTHER

Interventions

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Blood AM, IL-6, ACTH, Cortisol, Glucose and Insulin

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

OTHER_GOV

Sponsor Role collaborator

University of Sao Paulo

OTHER

Sponsor Role lead

Principal Investigators

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Thelma Okay, PHD

Role: STUDY_DIRECTOR

Childrens Institute / Molecular Biology

Locations

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Childrens Institute

São Paulo, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Martinez A, Weaver C, Lopez 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. doi: 10.1210/endo.137.6.8641217.

Reference Type RESULT
PMID: 8641217 (View on PubMed)

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. doi: 10.1097/01.sla.0000133253.45591.5b.

Reference Type RESULT
PMID: 15273558 (View on PubMed)

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. doi: 10.1006/jsre.2000.6013.

Reference Type RESULT
PMID: 11162047 (View on PubMed)

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):663-670. doi: 10.1213/01.ANE.0000072543.78106.AA.

Reference Type RESULT
PMID: 12933380 (View on PubMed)

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. doi: 10.18926/AMO/31995.

Reference Type RESULT
PMID: 11512567 (View on PubMed)

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. doi: 10.1291/hypres.26.s85.

Reference Type RESULT
PMID: 12630816 (View on PubMed)

Kapas S, Martinez 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. doi: 10.1677/joe.0.1560477.

Reference Type RESULT
PMID: 9582504 (View on PubMed)

Other Identifiers

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FMUSP/ cappesq 675/05

Identifier Type: -

Identifier Source: org_study_id