Nitric Oxide Generating Gel Dressing in Patients With Diabetic Foot Ulcers (ProNOx1)

A Clinical Pilot Study of an Oxides of Nitrogen Generating Gel Dressing System to Stimulate Healing in Diabetic Foot Ulcers

This is a 2 part study to assess the safety and efficacy of a nitric oxide (NOx) generating dressing on chronic diabetic foot ulcers (DFU). Nitric oxide has a range of effects on the body including vasodilation and angiogenesis. It is also a potent antimicrobial. This 140 patient, randomised, controlled clinical study will assess the ability of a simple 2 part, NOx generating dressing to increase blood flow in DFUs and to improve healing in chronic DFUs compared to standard of care.

Study Overview

• Status: Completed
• Conditions: Diabetic Foot Ulcer
• Intervention / Treatment: Device: NOx dressing; Other: Standard of Care

Detailed Description

This is a clinical study of a new wound dressing for diabetic foot ulcers (DFU). The dressing consists of 2 stable layers that when placed together release Nitric Oxide. In preclinical studies NOx delivery has caused significant vasodilation, angiogenesis and demonstrated potent anti-microbial activity.

In part 1 of the study, the dressing will be applied to up to 20 DFUs for a set period and the blood flow in and around the wound will be measured before and after application of the dressing. Any adverse events will be recorded.

If an increase in blood flow is seen and the dressing is well tolerated, part 2 will begin, which is a multi-centre, 120 patient, randomised, controlled study. 60 patients with chronic DFUs will be treated with the NOx generating dressing and 60 patients will continue to receive standard of care. The efficacy and the tolerability of the dressing will be measured.

The NOx dressing will be changed at least every 2 days and the standard of care changed as in normal clinical practice.

At weekly clinical visits the diameter, area and volume of the wound will be measured. The infective status of the wound will be assessed and the inflammatory profile of the wound will be measured.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Ninewells Hospital
  • Edinburgh, United Kingdom, EH16 4SA
    • Edinburgh Royal Infirmary
  • Glasgow, United Kingdom, G51 4TF
    • Southern General Hospital
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • Manchester, United Kingdom, M8 5RB
    • Pennine Acute Hospitals Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Preston, United Kingdom, PR2 9HT
    • Lancashire Teaching Hospitals
  • Salford, United Kingdom, M6 8HD
    • Salford Royal
  • Wakefield, United Kingdom, WF1 4DG
    • Pinderfields General Hospital
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • St James's University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged over 18 years.
• Diagnosed with type 1 or type 2 diabetes.
• With a chronic (present for at least 6 weeks) full-thickness foot ulcer (on or below the malleoli) not penetrating to tendon, periosteum or bone, and with a cross-sectional area between 25 and 2500 mm2.
• Patients must have pedal blood flow between normal and moderately ischaemic. Measurable as a palpable pedal pulse or in the absence of a palpable pedal pulse they must have a TcPO2 of ≥30mmHg or an ABPI of between 0.5-1.00, or > 1.2. (An ABPI of >1.2 is associated with calcification rather than ischaemia. We are including patients with an ABPI >1.2 because ABPI is measured in large arteries. NOx has the ability to dilate medium to small arterioles which are less likely to be calcified.)
• With some degree of neuropathy (as commonly seen in the Diabetes Foot Clinic).
• Able to read and understand the Volunteer Information Sheet and to provide meaningful written informed consent.
• Able and willing to follow the Protocol requirements.

Exclusion Criteria:

• Female patients who are pregnant or breast-feeding
• Any other serious disease likely to compromise the outcome of the trial
• Participation in any clinical study during the eight (8) weeks preceding the dosing period of the study
• Wound area greater than 2500 square mm;
• Patients with severe ischaemia. Measurable as absence of palpable pedal pulse and a TcPO2 of less than 30mmhg, or ABPI < 0.5 or between 1.0-1.2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm; Standard of Care	Other: Standard of Care; The clinician/podiatrist is free to use whichever treatment they would choose to use on the patient in their current clinical practice.
Experimental: Treatment Arm; NOx dressing applied and changed at least every 2 days for 12 weeks or until ulcer is healed.	Device: NOx dressing; The NOx dressing should be changed at least every 2 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure the safety of the NOx generating dressing	Number of participants with adverse events during the active study period and the following 3 months post treatment	Monitored at every visit until 12 weeks or ulcer is healed and at 3 month post treatment followed
Measure the efficacy of the NOx generating dressing	The time to healing of the ulcer will be measured and compared between the NOx generating dressing arm and the standard of care arm	Measured at every patient visit until healed or 12 weeks of treatment is reached

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure changes in ulcer blood flow.	In Part 1 of the study, blood flow in the ulcer will be measured by laser Doppler fluximetry before and after the NOx generating dressing is applied.	3 months
Measure changes in the inflammatory/infective status of the wounds.	Samples taken at every visit will be measured for microbial content and inflammatory cytokine presence and a comparison made between the 2 arms.	Samples taken at every visit until 12 weeks or the ulcer is healed
Measure the rate of repeat ulcers and breakdown in healing.		1 year

Collaborators and Investigators

• Sponsor: Edixomed Ltd
• Collaborators: Queen Mary University of London
• Investigators: Principal Investigator: Arthur Tucker, PhD, St Barts, London

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: October 24, 2013
• First Submitted That Met QC Criteria: November 6, 2013
• First Posted (Estimate): November 13, 2013

Study Record Updates

• Last Update Posted (Estimate): January 20, 2016
• Last Update Submitted That Met QC Criteria: January 19, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Diabetic; Nitric oxide; Chronic; Ulcers; Foot; Nitric oxide dressing; NOx; NOx dressing
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer; Ulcer
• Other Study ID Numbers: EDX 110