Effects of Growth Hormone on the Nitric Oxide Pathway

This study has been completed.
Sponsor:
Collaborator:
Pharmacia
Information provided by:
Hannover Medical School
ClinicalTrials.gov Identifier:
NCT00470002
First received: May 4, 2007
Last updated: NA
Last verified: May 2007
History: No changes posted
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effects of Growth Hormone (GH) on Parameters of the Nitric Oxide (NO) Pathway

Resource links provided by NLM:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Germany
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:
ClinicalTrials.gov Identifier: NCT00470002     History of Changes
Other Study ID Numbers: MES 03069, VP2-3900-4021576, IRB#3444
Study First Received: May 4, 2007
Last Updated: May 4, 2007
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

Additional relevant MeSH terms:
Cardiovascular Diseases
Hormones
Nitric Oxide
N,N-dimethylarginine
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014