The Role of S-nitrosohemoglobin in Regulating Systemic Blood Flow During Hypoxia and Normoxia

Focus is Determination of the Role of SNO-Hb in Forearm Blood Flow Regulation Clinical Trial

Official title:

The Role of S-nitrosohemoglobin in Regulating Systemic Blood Flow Under Hypoxic and Normoxic Conditions

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01905696
• Other study ID #: Pro00041312
• Status: Terminated
• Phase: Phase 0
• First received: April 30, 2013
• Last updated: December 28, 2016
• Start date: March 2013
• Est. completion date: August 2013

Study information

• Verified date: December 2016
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Nitric oxide is believed to contribute to regulation of blood flow by its selective binding to circulating hemoglobin (forming S-nitrosohemoglobin, SNO-Hb) and release in a PO2-dependent manner. This study is designed to test that hypothesis by measuring the effect of hypoxia and exercise on forearm blood flow before and after depletion of SNO-Hb using oral N-acetylcysteine.

Description:

NO has been shown to associate with erythrocytes in the form of SNO-Hb and can deliver vasomotor changes as erythrocytes pass through a physiologic O2 gradient. The aim of this study is to transiently deplete circulating SNO-Hb levels to prove that these levels are directly linked with the normal physiological vasodilation that occurs in response to brief hypoxia that occurs in moderate exercise. This study will be performed on healthy volunteers especially with no predisposing cardiovascular or respiratory conditions that may change their vasomotor response to hypoxia. Systemic blood flow will be approximated using non-invasive forearm venous occlusion plethysmography which will be performed initial to gather baseline data. The participants will then undergo 4 days of 600 mg BID oral N-acetylcysteine (NAC) solution treatment which acts as a bait reactant for NO groups bound to hemoglobin (SNO-Hb) and will then undergo retesting with forearm plethysmography. At the time of both blood flow measurements, arterial blood samples will also be gathered via an arterial catheter inserted on each of two testing days to determine SNO-Hb levels. Statistical analysis will include measuring the blunting of the hypoxia response and SNO-Hb levels using baseline testing as a self-control for each participant. Large scale human placebo-controlled trials with high-dose oral NAC (up to 8000 mg/day) for periods up to 12 months have shown no clinically significant adverse reactions, much less than in the proposed study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Pregnancy

• smoking

• pulmonary disease

• cardiovascular disease

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Focus is Determination of the Role of SNO-Hb in Forearm Blood Flow Regulation

Intervention

Drug:
• Oral N-acetylcysteine

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm blood flow		5 days	No