Effects of Growth Hormone on the Nitric Oxide Pathway - Full Text View

Sponsors and Collaborators:	Hannover Medical School Pharmacia
Information provided by:	Hannover Medical School
ClinicalTrials.gov Identifier:	NCT00470002

Purpose

The purpose of the study is to determine whether the treatment with growth hormone has an influence on the nitric oxide pathway in healthy males.

Condition	Intervention	Phase
Cardiovascular Disease	Drug: Somatropin	Phase I

Drug Information available for: Insulin Insulin-like growth factor I Mecasermin rinfabate Nitric oxide Somatotropin Somatropin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacodynamics Study
Official Title:	Effects of Growth Hormone (GH) on Parameters of the Nitric Oxide (NO) Pathway

Further study details as provided by Hannover Medical School:

Primary Outcome Measures:

Urinary nitrate excretion [ Time Frame: 10 days ]

Secondary Outcome Measures:

Insulin-like growth factor-1 in serum [ Time Frame: 10 days ]

Enrollment:	16
Study Start Date:	May 2004
Study Completion Date:	January 2005

Detailed Description:

Nitric oxide (NO) is a potent endogenous vasodilator and has shown to inhibit key processes of atherosclerosis like monocyte adhesion, platelet aggregation, and vascular smooth muscle cell proliferation. Impaired endothelial NO production is a main feature of endothelial dysfunction, which by itself is an early step in the course of atherosclerotic vascular disease.

Recent studies could confirm this close association between parameters of the NO pathway and cardiovascular disease and could further enhance the knowledge on the pathophysiological mechanisms. There is a significant relationship between insulin resistance and the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA). Moreover, evidence could be provided that plasma levels of ADMA are a strong and independent predictor of mortality and cardiovascular outcome in haemodialysis patients.

Patients with growth hormone deficiency are characterized by a 1.9 fold higher risk of death from cardiovascular disease. Again, there is good evidence, that alterations of the NO-pathway are involved in this increase of cardiovascular risk. A reduced endogenous systemic production of NO was found in patients with growth hormone deficiency, treatment with recombinant growth hormone normalized NO production. The effects of growth hormone on NO are possibly mediated by insulin-like growth factor-I (IGF-I), which stimulates NO synthesis in vitro. The onset of IGF-I increase in healthy volunteers treated with GH is evident after 12 h, the maximum effect takes place between 5 to 8 days. Also in adults with growth hormone deficiency, the major effects of growth hormone treatment on IGF-I levels are observed within 2 weeks. After discontinuation of growth hormone therapy, IGF-1 levels return to base line within 2-3 days.

The aim of the present study is to further elucidate the in vivo effects of GH on the NO pathway and NO mediated cardiovascular functions.

Eligibility

Ages Eligible for Study:	50 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy male subjects without recent severe diseases
Age 50 yrs or older
Body mass index at or below 30 kg/m2
Insulin-like growth factor-1 level below 200 ng/ml
Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial
Subjects that are willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

History of any severe hepatic, renal, cardiac, endocrine, metabolic, or malignant diseases
Requirement for medical drug treatment
Growth hormone treatment during the last 12 months
Drug dependence, alcohol or nicotine abuse
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the investigator, would make the subject inappropriate for entry into this study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00470002

Locations

Germany, Lower Saxony
Institute of Clinical Pharmacology, Hannover Medical School
Hannover, Lower Saxony, Germany, 30623

Sponsors and Collaborators

Hannover Medical School

Pharmacia

Investigators

Study Director:

Dirk O Stichtenoth, MD

Institute of Clinical Pharmacology, Hannover Medical School

More Information

Publications:

Boger RH, Skamira C, Bode-Boger SM, Brabant G, von zur Muhlen A, Frolich JC. Nitric oxide may mediate the hemodynamic effects of recombinant growth hormone in patients with acquired growth hormone deficiency. A double-blind, placebo-controlled study. J Clin Invest. 1996 Dec 15;98(12):2706-13.

Tsukahara H, Gordienko DV, Tonshoff B, Gelato MC, Goligorsky MS. Direct demonstration of insulin-like growth factor-I-induced nitric oxide production by endothelial cells. Kidney Int. 1994 Feb;45(2):598-604.

Study ID Numbers:	MES 03069, VP2-3900-4021576, IRB#3444
Study First Received:	May 4, 2007
Last Updated:	May 4, 2007
ClinicalTrials.gov Identifier:	NCT00470002
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Hannover Medical School:

growth hormone
nitric oxide
nitrate
cyclic guanosine monophosphate

insulin-like growth factor-1
asymmetric dimethylarginine
blood pressure
endothelial progenitor cells

Study placed in the following topic categories:

Nitric Oxide
N,N-dimethylarginine
Insulin

Additional relevant MeSH terms:

Respiratory System Agents
Vasodilator Agents
Neurotransmitter Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Asthmatic Agents
Cardiovascular Agents
Protective Agents

Pharmacologic Actions
Autonomic Agents
Therapeutic Uses
Free Radical Scavengers
Endothelium-Dependent Relaxing Factors
Cardiovascular Diseases
Peripheral Nervous System Agents
Bronchodilator Agents

ClinicalTrials.gov processed this record on January 14, 2009