Carnosine for Peripheral Vascular Disease
-
- STATUS
- Recruiting
-
- End date
- Dec 31, 2022
-
- participants needed
- 104
-
- sponsor
- Monash University
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- in the ischaemic leg.
Aims
Aim 1: Determine whether in patients with PVD, carnosine in addition to exercise improves:
- walking endurance (6-min walk test; primary outcome);
- initial claudication distance (ICD), and absolute claudication distance (ACD; treadmill), cadence, resting and exercise ABI; and
- central blood pressure, endothelial function, arterial (aortic) stiffness, lipid profile; and
- quality of life as determined by EuroQol-5D (all secondary outcomes).
- 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:
- 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.
- 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.
Description
Peripheral vascular disease (PVD) has high prevalence of 10-15% in Australia and is caused by atherosclerotic occlusion of the arteries supplying the lower extremities which reduces blood flow and leads to intermittent claudication and critical limb ischaemia. No effective medication is currently available. Although surgical or endovascular revascularisation are available treatments, not all patients are suitable for the procedure, and grafts can fail, and dilated arteries can restenose. Structured exercise, both supervised and home-based, improves walking endurance in patients with PVD to a similar extent as revascularisation and effects are longer lasting but the pain associated with exercise is a major limitation. Therefore, there is a need to develop safe interventions synergistic with exercise that can prompt revascularisation and preserve limb viability.
Angiogenesis plays an essential role for recovery from critical limb ischaemia. Hypoxia inducible factor 1 (HIF1-), a master regulator of angiogenic genes, has been implicated . Under normal conditions, HIF1- is targeted for proteasomal degradation through the activity of prolyl hydroxylases (PHDs). PHDs require iron for their activity and their inactivation by metal chelators or pharmacological inhibitors stabilises HIF1- and has been shown to improve blood flow in the ischaemic limb. However, metal chelators cannot be used as an intervention due to their toxicity.
Recent studies have shown that supplementation of carnosine (-alanyl-L-histidine), a naturally occurring histidyl dipeptide in skeletal muscle with an excellent safety profile, improves exercise performance in athletes as well as in patients with chronic heart failure. The investigators and others have shown that carnosine supplementation also improves cardiometabolic risk factors. No clinical trial has yet to investigate whether carnosine improves walking endurance in patients with PVD. Carnosine has anti-inflammatory, antioxidative, anti-glycating and anti-atherosclerotic properties. It also has the ability to chelate metals, form conjugates with reactive aldehydes, and has lactate buffering capacity. In addition, carnosine has been found to be very effective in reducing ischaemia-reperfusion damage in several organs. Our preliminary results using a murine model of hind limb ischaemia (HLI) showed that administration of carnosine over 21 days increased HIF1-a and VEGF levels in the ischaemic muscle and improved tissue perfusion. Furthermore, mobilisation of pro-angiogenic endothelial progenitor cells (EPCs) and the ambulatory movement were increased in carnosine treated HLI mice compared to controls. The investigators propose a randomised clinical trial to investigate whether administration of carnosine for 6-month in addition to exercise could improve walking endurance and quality of life in patients with PVD compared to placebo and exercise.
Details
| Condition | Peripheral vascular disease, Circulation Disorders, Peripheral vascular disease, peripheral arterial disease, Peripheral Arterial Disease (PAD), Circulation Disorders, Peripheral Arterial Disease (PAD), peripheral arterial diseases, peripheral artery disease |
|---|---|
| Treatment | Placebo, carnosine |
| Clinical Study Identifier | NCT03844113 |
| Sponsor | Monash University |
| Last Modified on | 27 January 2021 |
How to participate?
,
You have contacted , on
Your message has been sent to the study team at ,
What happens next?
- You can expect the study team to contact you via email or phone in the next few days.
- Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.
You are contacting
Primary Contact
Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.
Learn moreIf you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Learn moreComplete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.
Learn moreSimilar trials to consider
Not finding what you're looking for?
Sign up as a volunteer to stay informed
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.
Sign up as volunteer