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

NCT03077763 | Unknown Phase 1

• 1 other identifier: 206995
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

nitrite; haemoglobin; normoxia; hypoxia; vasodilatation; blood

Outcome Measures

Primary Outcomes (1)

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

  Up to 18 months

Secondary Outcomes (5)

• Change in FBFR during haemolysed blood infusion vs baseline

  Up to 18 months

• Change in FBFR during nitrite infusion in normoxia vs nitrite infusion in hypoxia

  Up to 18 months

• Change in FBFR during nitrite infusion in normoxia vs baseline

  Up to 18 months

• Change in FBFR during nitrite infusion in hypoxia vs baseline

  Up to 18 months

• Blood analysis (cell free haemoglobin, nitrate, nitrite and nitroso species levels)

  Up to 18 months

Study Arms (2)

Normoxia and Nitrite (3umol/min-1)

ACTIVE COMPARATOR

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

Drug: Sodium Nitrite

Hypoxia and Nitrite (1umol/min-1)

ACTIVE COMPARATOR

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).

Drug: Sodium Nitrite

Interventions

Sodium Nitrite DRUG

Hypoxia and Nitrite (1umol/min-1); Normoxia and Nitrite (3umol/min-1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of East Anglia: lead

Study Sites (1)

University of East Anglia

Norwich, Norfolk, NR4 7UQ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Hypoxia; Aneurysm

Interventions

Sodium Nitrite

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Nitrites; Nitrous Acid; Nitrogen Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Michael P Frenneaux, FRCP, FESC

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas D Gollop, MRCP(UK)

CONTACT

01603 591790; n.gollop@uea.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2016
• First Posted: March 13, 2017
• Study Start: December 1, 2016
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2018
• Last Updated: March 20, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)