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

Healthy Volunteers Clinical Trial

Official title:

The Effects of Free Haemoglobin NO-blockade on Nitrite Forearm Vessel Dilatation Under Normoxia and Hypoxia in Healthy Volunteers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03077763
• Other study ID #: 206995
• Status: Recruiting
• Phase: Phase 1
• First received: September 20, 2016
• Last updated: March 17, 2017
• Start date: December 2016
• Est. completion date: March 2018

Study information

• Verified date: March 2017
• Source: University of East Anglia
• Contact: Nicholas D Gollop, MRCP(UK)
• Phone: 01603 591790
• Email: n.gollop[@]uea.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 41
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Sodium Nitrite

Locations

Country	Name	City	State
United Kingdom	University of East Anglia	Norwich	Norfolk

Sponsors (1)

Lead Sponsor	Collaborator
University of East Anglia

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FBFR during intra-brachial nitrite and haemolysed blood co-infusion in normoxia vs hypoxia.		Up to 18 months
Secondary	Change in FBFR during haemolysed blood infusion vs baseline		Up to 18 months
Secondary	Change in FBFR during nitrite infusion in normoxia vs nitrite infusion in hypoxia		Up to 18 months
Secondary	Change in FBFR during nitrite infusion in normoxia vs baseline		Up to 18 months
Secondary	Change in FBFR during nitrite infusion in hypoxia vs baseline		Up to 18 months
Secondary	Blood analysis (cell free haemoglobin, nitrate, nitrite and nitroso species levels)		Up to 18 months