Peripheral arterial Disease
Conditions
Interventions
Product Name: Inorganic Sodium Nitrate
Pharmaceutical Form: Capsule
INN or Proposed INN: Sodium Nitrate Powder
CAS Number: 7631-99-4
Con
Sponsors
University of Aberdeen
University of Aberdeen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with stable intermittent claudication 1) of at least 3 months duration 2) with clinical findings of peripheral vascular disease and 3) an ABPI=65 years) yes F.1.3.1 Number of subjects for this age range 132
Exclusion criteria
Exclusion criteria: Patients with the following will be excluded: • rest pain or ulceration • recent arterial revascularisation (within the past 3 months) • other co-morbidities that may impede the patient’s ability to perform an exercise test (arthritis, severe coronary artery disease or chronic obstructive pulmonary disease) • Patients on clopidogrel • oral nitrate preparations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: to determine the effect of inorganic Sodium Nitrate (daily dose of 7mmol) for six weeks compared to placebo in respect of: 1) treadmill absolute walking distance. 2) and quality of life in patients with stable intermittent claudication and in a subgroup of 20 patients: 4) Skeletal muscle perfusion will be assessed using MRI 5) Skeletal muscle biopsies will be taken to assess mitochondrial function ; Secondary Objective: Secondary objectives: In order to define the mechanism(s) responsible the following will be assessed: 1) Plasma markers of angiogenesis, NO signaling and anaerobic metabolism 2) Markers of endothelial function 3) Markers of platelet activity ; Primary end point(s): Primary end points: Clinical outcome measures 1. Maximal walking distance and initial claudication distance will be assessed using the Skinner Gardner variable-grade constant speed treadmill protocol will be performed twice at baseline, and following 6 weeks of placebo/sodium nitrate. 2. Quality of life: Generic SF36, disease specific VascuQOL and Walking impairment questionnaire: will be measured at baseline, and 6 weeks ;Timepoint(s) of evaluation of this end point: The treadmill test will be performed twice prior to the patient starting the study and once at 6 weeks. The Quality of life questionnaires will be performed at baseline and after six weeks of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end point: In order to define the mechanism(s) responsible for anti-ischaemic effects in the legs a series of studies will be conducted to assess whether these are related to improved perfusion, and if so whether this is due to increased angiogenesis of whether these effects are attributable to effects on skeletal muscle mitochondrial function. 1 Plasma markers of angiogenesis, NO signaling and anaerobic metabolism: Plasma concentrations of VEGF, nitrite, nitrate, and lactate will be measured prior to and immediately after maximum walking distance in all patients. 2. Markers of endothelial activity: vWF and soluble P selectin (all patients) 3. Pulse wave velocity & stiffness index: PWV will be measured by the fully automated micromedical pulse trace PWV (PT 4000, Rochester, Kent) and stiffness index is measured via the use of photoplethysmography (all patients). This will be measured prior to exercise. Blood pressure: measured by the Datascope accutor plus (Datascope Medical company).Three supine blood pressure measurements will be taken 1 minute apart after a 10 minute rest, and the average of these readings will be used in the analysis. This will be recorded just prior to measuring the pulse wave velocity 5. Platelet function assays: In 100 patients platelet aggregation measured by Ultegra RPFA point of care and flow cytometry ( P-selectin expression, fibrinogen binding with and without ADP stimulation and platelet-monocyte aggregtes) will be measured prior to and immediately after maximum walking distance In a subgroup of 20 patients: 1. Skeletal muscle perfusion will be assessed using MRI (subgroup of 20 patients) 2. Skeletal muscle biopsies will be taken – for analysis of glycogen and triglyceride content, expression and acivity of metabolic enzymes, UCP expression and mitochondrial electron tra | — |
Countries
United Kingdom
Contacts
Public ContactHolland
Outcome results
None listed