The Healing Effect of a Two-Herb Recipe on Foot Ulcer in Chinese Patients With Type 2 Diabetes
Condition: Diabetic Foot Ulcer
MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Detailed 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
    

Intervention name(s): Chinese herbal medicine (Radix Rehmanniae and Radix Astragali); Placebo comparator
Intervention type(s): Drug; Drug
Intervention description(s): 2 sachets to be taken daily; 2 sachets to be taken daily
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Diabetes; foot ulcer; Chinese herbal medicine