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

NCT ID: NCT03077763

Last Updated: 2017-03-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2018-03-31

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.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Normoxia and Nitrite (3umol/min-1)

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

Group Type: ACTIVE_COMPARATOR

Sodium Nitrite

Intervention Type: DRUG

Hypoxia and Nitrite (1umol/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).

Group Type: ACTIVE_COMPARATOR

Sodium Nitrite

Intervention Type: DRUG

Interventions

Sodium Nitrite

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of East Anglia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael P Frenneaux, FRCP, FESC

Role: PRINCIPAL_INVESTIGATOR

Dean of Medicine, Norwich Medical School, The University of East Anglia, UK

Locations

University of East Anglia

Norwich, Norfolk, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Nicholas D Gollop, MRCP(UK)

Role: CONTACT

n.gollop@uea.ac.uk

01603 591790 ext. 1790

Facility Contacts

Nicholas D Gollop, MRCP

Role: primary

n.gollop@uea.ac.uk

01603 591790 ext. 1790

Other Identifiers

206995

Identifier Type: -

Identifier Source: org_study_id