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The Haem and Nitrite Study - The Effects of Haemoglobin NO-blockade on Nitrite-induced Forearm Vessel Dilatation

Primary Purpose

Healthy Volunteers

Status
Unknown status
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Sodium Nitrite
Sponsored by
University of East Anglia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Healthy Volunteers focused on measuring nitrite, haemoglobin, normoxia, hypoxia, vasodilatation, blood

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Male or female, aged greater than or equal to 18 years
  2. If between 18-20 years of age, calculate total blood volume should be more than >3.5L (http://www.blood.co.uk/giving-blood/who-can-give-blood/)
  3. Body weight > 50kg weight (8 stone 12lbs)
  4. Not known to have any significant past medical history and not having regular follow up (Check Donor Selection Guidelines (http://www.transfusionguidelines.org.uk/)
  5. Willing to provide blood donation and receive autologous blood transfusion
  6. After assessment for eligibility pass all blood donor eligibility criteria
  7. Able to provide informed consent
  8. Should inform overseas travel plan during study period (Check Geographical Disease Risk Index on http://www.transfusionguidelines.org.uk/dsg/gdri) e.g. unable to donate blood for 6 months if travel in a malaria endemic country. Similar guidelines for West Nile virus and T. Cruzi endemic countries.

Exclusion Criteria:

  1. Significant medical, surgical or psychiatric disease that in the opinion of the Clinical Research Fellow would affect subject safety or significantly impact his/her ability to comply with follow-up. This would include any known clotting disorders.
  2. Known allergy or intolerance to Nitrites
  3. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
  4. Female subjects must be of non-childbearing potential, defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to enrolment
  5. Receipt of an investigational drug or biological agent within the 4 weeks prior to study entry or 5 times the drug half-life, whichever is the longer
  6. Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease.
  7. No past history of significant adverse events post blood donation

Sites / Locations

  • University of East AngliaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Normoxia and Nitrite (3umol/min-1)

Hypoxia and Nitrite (1umol/min-1)

Arm Description

Sodium nitrite stock solution: 100umol/10ml, prepared to concentration according to oxygen sequence. Normoxia (3umol/min-1).

This will be repeated as per the normoxia cohort, but at a reduced dose of sodium nitrite (1umol/min-1 for 30 minutes) and the volunteers will be asked to breathe 12% oxygen/88% nitrogen for 1-5 minutes before Plethysmography is performed (to get the volunteer to an oxygen saturation of 83-88% peripherally).

Outcomes

Primary Outcome Measures

Change in FBFR during intra-brachial nitrite and haemolysed blood co-infusion in normoxia vs hypoxia.

Secondary Outcome Measures

Change in FBFR during haemolysed blood infusion vs baseline
Change in FBFR during nitrite infusion in normoxia vs nitrite infusion in hypoxia
Change in FBFR during nitrite infusion in normoxia vs baseline
Change in FBFR during nitrite infusion in hypoxia vs baseline
Blood analysis (cell free haemoglobin, nitrate, nitrite and nitroso species levels)

Full Information

First Posted
September 20, 2016
Last Updated
March 17, 2017
Sponsor
University of East Anglia
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1. Study Identification

Unique Protocol Identification Number
NCT03077763
Brief Title
The Haem and Nitrite Study - The Effects of Haemoglobin NO-blockade on Nitrite-induced Forearm Vessel Dilatation
Official Title
The Effects of Free Haemoglobin NO-blockade on Nitrite Forearm Vessel Dilatation Under Normoxia and Hypoxia in Healthy Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Unknown status
Study Start Date
December 2016 (Actual)
Primary Completion Date
March 2018 (Anticipated)
Study Completion Date
March 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of East Anglia

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The study is a pharmacodynamic random order cross-over trial investigating the physiological effects of intra-arterial infusion of nitrite following a haemolysed autologous blood transfusion.
Detailed Description
This is a healthy volunteer study. Following entry into this cross-over trial, participants will be randomized to undergo experiments under either normoxic followed by hypoxic conditions, or hypoxic followed by normoxic conditions. Subjects will donate whole blood as an autologous unit at a preselected NHSBT donation site. The unit will transported back to the NNUH blood bank after a minimum of 30 days (maximum 35 days) after donation. Volunteers will be tested for baseline bloods. Volunteers will be randomised to normoxia or hypoxia. The will then undergo a nitrite infusion, followed by an autologous whole blood transfusion and a second nitrite infusion (which will co-infuse at the end of the transfusion). During the protocol, the participants will undergo repeated FBFR measurements using strain-gauge plethysmography. After a minimum of 12 weeks rest period after their initial donation, participants will cross-over to the opposite oxygen condition (as per initial randomization) and the above protocol will be repeated. All interventions will be performed by fully trained and competent medical staff.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers
Keywords
nitrite, haemoglobin, normoxia, hypoxia, vasodilatation, blood

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Normoxia and Nitrite (3umol/min-1)
Arm Type
Active Comparator
Arm Description
Sodium nitrite stock solution: 100umol/10ml, prepared to concentration according to oxygen sequence. Normoxia (3umol/min-1).
Arm Title
Hypoxia and Nitrite (1umol/min-1)
Arm Type
Active Comparator
Arm Description
This will be repeated as per the normoxia cohort, but at a reduced dose of sodium nitrite (1umol/min-1 for 30 minutes) and the volunteers will be asked to breathe 12% oxygen/88% nitrogen for 1-5 minutes before Plethysmography is performed (to get the volunteer to an oxygen saturation of 83-88% peripherally).
Intervention Type
Drug
Intervention Name(s)
Sodium Nitrite
Primary Outcome Measure Information:
Title
Change in FBFR during intra-brachial nitrite and haemolysed blood co-infusion in normoxia vs hypoxia.
Time Frame
Up to 18 months
Secondary Outcome Measure Information:
Title
Change in FBFR during haemolysed blood infusion vs baseline
Time Frame
Up to 18 months
Title
Change in FBFR during nitrite infusion in normoxia vs nitrite infusion in hypoxia
Time Frame
Up to 18 months
Title
Change in FBFR during nitrite infusion in normoxia vs baseline
Time Frame
Up to 18 months
Title
Change in FBFR during nitrite infusion in hypoxia vs baseline
Time Frame
Up to 18 months
Title
Blood analysis (cell free haemoglobin, nitrate, nitrite and nitroso species levels)
Time Frame
Up to 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female, aged greater than or equal to 18 years If between 18-20 years of age, calculate total blood volume should be more than >3.5L (http://www.blood.co.uk/giving-blood/who-can-give-blood/) Body weight > 50kg weight (8 stone 12lbs) Not known to have any significant past medical history and not having regular follow up (Check Donor Selection Guidelines (http://www.transfusionguidelines.org.uk/) Willing to provide blood donation and receive autologous blood transfusion After assessment for eligibility pass all blood donor eligibility criteria Able to provide informed consent Should inform overseas travel plan during study period (Check Geographical Disease Risk Index on http://www.transfusionguidelines.org.uk/dsg/gdri) e.g. unable to donate blood for 6 months if travel in a malaria endemic country. Similar guidelines for West Nile virus and T. Cruzi endemic countries. Exclusion Criteria: Significant medical, surgical or psychiatric disease that in the opinion of the Clinical Research Fellow would affect subject safety or significantly impact his/her ability to comply with follow-up. This would include any known clotting disorders. Known allergy or intolerance to Nitrites Known glucose-6-phosphate dehydrogenase (G6PD) deficiency Female subjects must be of non-childbearing potential, defined as follows: postmenopausal females who have had at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhoea with serum FSH>40mIU/ml or females who have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy at least 6 weeks prior to enrolment Receipt of an investigational drug or biological agent within the 4 weeks prior to study entry or 5 times the drug half-life, whichever is the longer Predisposed to acute on chronic limb ischemia evident from a history of claudication or known peripheral arterial disease. No past history of significant adverse events post blood donation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nicholas D Gollop, MRCP(UK)
Phone
01603 591790
Ext
1790
Email
n.gollop@uea.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael P Frenneaux, FRCP, FESC
Organizational Affiliation
Dean of Medicine, Norwich Medical School, The University of East Anglia, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of East Anglia
City
Norwich
State/Province
Norfolk
ZIP/Postal Code
NR4 7UQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicholas D Gollop, MRCP
Phone
01603 591790
Ext
1790
Email
n.gollop@uea.ac.uk

12. IPD Sharing Statement

Plan to Share IPD
No

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The Haem and Nitrite Study - The Effects of Haemoglobin NO-blockade on Nitrite-induced Forearm Vessel Dilatation

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