The Healing Effect of a Two-Herb Recipe on Foot Ulcer in Chinese Patients With Type 2 Diabetes

Diabetic Foot Ulcer Clinical Trial

Official title: The Healing Effect of a Two-Herb Recipe on Foot Ulcer in Chinese Patients With Type 2 Diabetes: A Randomized, Placebo-Controlled Study

Status Completed

Clinical Trial Summary

There is now a global epidemic of diabetes and obesity affecting more than 300 million people worldwide with Asia in the forefront. In Hong Kong, diabetes affects more than 10% of the population. Patients with diabetes have a 12—25% lifetime risk of developing a foot ulcer.The abnormal metabolic milieus of hyperglycemia, hyperlipidemia, hypertension, pro-thrombotic state and chronic inflammation in diabetes causes atherosclerosis.A significant proportion of subjects have underlying peripheral arterial disease and neuropathy. These subjects are at great risk of developing infective foot ulceration secondary to impaired vascular supply, sensory loss and minor trauma.Without prompt and proper medical treatment, these infective ulcers will deteriorate leading to gangrene and limb amputation. In-vitro and in-vivo studies revealed that 5 out of the 12 herbs were effective in promoting fibroblast proliferation and angiogenesis. To minimize potential drug interactions and adverse effects from multiple components in a recipe of Traditional Chinese Medicine (TCM), the investigators have developed a simplified formula from the 12 herbs consisting of only two herbs. In this proof-of-concept study, the investigators hypothesize that the novel recipe of herbal medicine will expedite healing of early foot ulcer by promoting vascularisation and granulation as well as modulating inflammatory response.

Clinical Trial Description

There is now a global epidemic of diabetes and obesity affecting more than 300 million people worldwide with Asia in the forefront. In Hong Kong, diabetes affects more than 10% of the population. Patients with diabetes have a 12—25% lifetime risk of developing a foot ulcer. These silent conditions independently and collectively contribute to 50% of all causes of death mainly due to cardiovascular and renal complications. Type 2 diabetes is a complex disorder characterized by a constellation of cardiovascular risk factors, notably, hyperglycemia, obesity, dyslipidemia (high triglyceride (TG) and low HDL-C), hypertension, microinflammation and prothrombotic state, often referred to as the metabolic syndrome. The public health implication of diabetes lies mainly in its devastating chronic complications due to generalized vascular dysfunction. In patients with diabetes and metabolic syndrome, loss of cellular structure or function due to apoptosis, angiogenesis and fibrosis eventually manifest as overt diabetic complications, such as cardiovascular diseases, neuropathy, retinopathy and nephropathy.

The abnormal metabolic milieus of hyperglycemia, hyperlipidemia, hypertension, pro-thrombotic state and chronic inflammation in diabetes causes atherosclerosis. A significant proportion of subjects have underlying peripheral arterial disease and neuropathy. These subjects are at great risk of developing infective foot ulceration secondary to impaired vascular supply, sensory loss and minor trauma. Without prompt and proper medical treatment, these infective ulcers will deteriorate leading to gangrene and limb amputation. Age, wound depth, the presence of ischaemia, a low albumin level, and the lack of simultaneous ulceration are the most significant independent predictors of an unfavourable outcome. The conventional management of diabetic foot ulcer includes rest, antibiotic therapy, surgical debridement and good glycemic control. The investigators previously demonstrated that the use of a recipe containing 12 herbs was effective in promoting the healing of severe chronic non-healing diabetic foot ulcers and achieved an 85% of limb preservation. In-vitro and in-vivo studies revealed that 5 out of the 12 herbs were effective in promoting fibroblast proliferation and angiogenesis. To minimize potential drug interactions and adverse effects from multiple components in a recipe of Traditional Chinese Medicine (TCM), the investigators have developed a simplified formula from the 12 herbs consisting of only two herbs.

Many herbs have long been used to treat diabetes mellitus and its complications. In many of these successful attempts Radix Rehmanniae (RR) and Radix Astragali (RA) have frequently been used in combination with other herbs to form complex formulae such as 'blood-house blood stasis-dispelling decoction with additive ingredients' and 'pills of six drugs with Rehmannia'.

Based on our previous in-vitro and in-vivo studies, a new reformulated recipe of herbal medicine has been developed. In this proof-of-concept study, the investigators hypothesize that the novel recipe of herbal medicine will expedite healing of early foot ulcer by promoting vascularisation and granulation as well as modulating inflammatory response. Results will provide valuable insight and understanding of the application of TCM in the management of diabetic foot ulcer, in particular, the effect on angiogenesis and anti-inflammation. New intellectual properties will be developed and provide the foundation for future research. Such an integrated approach from bench to bedside will serve as a model platform for the development of TCM in Hong Kong.

The study will investigate whether the two-herb recipe can increase the wound healing of patients with diabetes mellitus.

Primary outcome:

1. Resolution/progression of foot ulcer based on PEDIS

2. Failure of treatment i.e. no improvement in 6 months, rapid deterioration or emergency surgery required

Secondary outcome:

1. Hospital admission/attendance/stay

2. Metabolic parameters ;

Related Conditions & MeSH terms

• Diabetic Foot
• Diabetic Foot Ulcer
• Foot Ulcer
• Ulcer

• NCT number: NCT01389362
• Study type: Interventional
• Source: Chinese University of Hong Kong
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 2009
• Completion date: May 2011