Carnosine for Peripheral Vascular Disease

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The investigators hypothesise that a home-based standardised exercise intervention with 2g of carnosine daily for 6 months will improve walking endurance in 104 patients with PVD aged 40-80 years compared to placebo and exercise through stabilisation of HIF1-α in the ischaemic leg.

Aims

Aim 1: Determine whether in patients with PVD, carnosine in addition to exercise improves:

1. walking endurance (6-min walk test; primary outcome);

2. initial claudication distance (ICD), and absolute claudication distance (ACD; treadmill), cadence, resting and exercise ABI; and

3. central blood pressure, endothelial function, arterial (aortic) stiffness, lipid profile; and

4. quality of life as determined by EuroQol-5D (all secondary outcomes).

5. Improve cognitive function (global cognitive score formed by a composite of 7 cognitive tests)

Aim 2: Delineate the mechanisms by which carnosine improves walking endurance:

1. protein expression of pro-angiogenic and carnosine related genes, including carnosine transporters in the skeletal muscle biopsies, EPCs in peripheral blood and quantitative proteomic studies.

2. other mechanisms demonstrated in animal studies including plasma inflammatory markers, serum and urinary advanced glycation (AGE) and lipoxidation (ALE) end-products (tertiary outcomes).

This trial will provide evidence for use of carnosine as a therapeutic intervention for PVD patients and, if positive, will have immediate clinical application.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Monash University
• Collaborator: Monash Health

Criteria

Inclusion Criteria:

• Age >=40or <80 years

• Clinical diagnosis Peripheral Vascular disease

• Rutherford Grade 1-3

• No significant kidney, cardiovascular, haematological, respiratory, gastrointestinal, or central nervous system disease, as well as no psychiatric disorders, no active cancer within the last five years; no presence of acute inflammation (by history, physical or laboratory examination)

• Intermittent claudication on treadmill between 30m and 200m

• Ankle Brachial index 0.6-1 at rest with minimum post exercise drop in ABI of 0.1

Exclusion Criteria:

• Age < 40 or > 80 years

• Pregnant or lactating

• Limb threatening ischaemia- Rutherford grades 4-6, manifested by ischaemic rest pain, ulceration, or gangrene; acute limb-threatening ischaemia

• lower limb surgical or endovascular interventions in the preceding 6 months

• planned lower limb endovascular or surgical intervention within the next 6 months on either limb

• taking medication for PVD (Cilostazol and Pentoxifylline)

• inability to complete the treadmill walking test for reasons other than claudication

• myocardial infarction within last 3 months

• deep vein thrombosis within 3 months

• estimated life expectancy < 1 year

• alcohol and illicit drug abuse.