Diabetic Foot UlcerPhase 2/3NCT01389362
The Healing Effect of a Two-Herb Recipe on Foot Ulcer in Chinese Patients With Type 2 Diabetes
A Phase 2/3 study testing Chinese herbal medicine (Radix Rehmanniae and Radix Astragali) in people with Diabetic Foot Ulcer, run by Chinese University of Hong Kong at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Diabetic Foot Ulcer
- What is being tested?
- Chinese herbal medicine (Radix Rehmanniae and Radix Astragali)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteChina
- Study dates
- May 2009to May 2011
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2 diabetic subjects with documented evidence of mild diabetic foot ulcer
- Male or female patients attending Diabetic Clinics and/or Podiatry Clinics at the hospitals of the New Territories East Cluster
- Aged between 20 and 75 years old inclusive
- All patients should be on stable dose of medication 4 weeks prior to enrolment
- Written informed consent
- If the patient is a woman of child-bearing potential, she must agree to use adequate method of contraception throughout the study period, unless surgically sterilized.
Who cannot join
- Patients with end-stage renal disease as defined by the need for dialysis or on renal replacement program
- Patients with advanced diabetic eye disease as defined by the history of laser therapy, retinal detachment or vitreous hemorrhage
- Pregnancy, breast feeding, or patient has plans of becoming pregnant during the study period.
- Known allergy to TCM drugs
- Contraindication or intolerance to use of aspirin, statin , ACEI or ARB
- History of major gastrointestinal bleeding in the 5 years prior to consent
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- Congestive heart failure of any severity
- Significant cardiovascular disease within 3 months of enrolment including acute coronary syndrome, cardiac revascularization procedure, transient ischemic attack and cerebrovascular accident
- HbA1c ≥ 10%
- Severe liver function impairment (≥ 3 ULN of ALT) and renal impairment (eGFR < 30 ml/min/1.73 m2)
- Investigational drugs within 30 days of enrolment
- Patient taking any Chinese herbal medicine in the 8 weeks prior to enrolment into the study
- Any other medical conditions that is considered as unsuitable for the study by investigator
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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:
- Resolution/progression of foot ulcer based on PEDIS
- Failure of treatment i.e. no improvement in 6 months, rapid deterioration or emergency surgery required
Secondary outcome:
- Hospital admission/attendance/stay
- Metabolic parameters
- Conditions
- Diabetic Foot Ulcer
- Being tested
- Chinese herbal medicine (Radix Rehmanniae and Radix Astragali), Placebo comparator
- Keywords
- Diabetes, foot ulcer, Chinese herbal medicine
- Medical subject headings
- Diabetic Foot, Diabetes Mellitus, Foot Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chinese herbal medicine (Radix Rehmanniae and Radix Astragali)Drug
2 sachets to be taken daily
Placebo comparatorDrug
2 sachets to be taken daily
| Study group | Role | What they receive |
|---|---|---|
| Chinese Herbal Medicine | Active comparator | 2 sachets of Chinese Herbal Medicine to be taken daily Receives: Drug: Chinese herbal medicine (Radix Rehmanniae and Radix Astragali) |
| Placebo arm | Placebo comparator | 2 sachets to be taken daily Receives: Drug: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resolution/progression of foot ulcer based on PEDIS
Measured: 6 months
Secondary outcomes (1)
Hospital admission/attendance/stay
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2011 (estimated)
- Study startMay 2009
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Foot UlcerStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Investigators
- Juliana NA Chan, MBChB, FRCP, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01389362
- Sponsor's protocol ID
- CRE-2008.581
- Status last verified
- Jul 2011
- First submitted
- 6 Jul 2011
- Last updated
- 28 Jul 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ko CH, Yi S, Ozaki R, Cochrane H, Chung H, Lau W, Koon CM, Hoi SW, Lo W, Cheng KF, Lau CB, Chan WY, Leung PC, Chan JC. Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with diabetes: a randomized double-blind placebo-controlled study. J Diabetes. 2014 Jul;6(4):323-34. doi: 10.1111/1753-0407.12117. Epub 2014 Feb 24.
PubMed 24330156
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01389362
- Acronym / sponsor ID
- CRE-2008.581
- Conditions
- Diabetic Foot Ulcer
- Keywords
- Diabetes, foot ulcer, Chinese herbal medicine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- May 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 8 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Resolution/progression of foot ulcer based on PEDIS
- Failure of treatment i.e. no improvement in 6 months, rapid deterioration or emergency surgery required
Secondary outcome:
- Hospital admission/attendance/stay
- Metabolic parameters
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chinese Herbal Medicine | Active comparator | Drug: Chinese herbal medicine (Radix Rehmanniae and Radix Astragali)2 sachets of Chinese Herbal Medicine to be taken daily |
| Placebo arm | Placebo comparator | Drug: Placebo comparator2 sachets to be taken daily |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Type 2 diabetic subjects with documented evidence of mild diabetic foot ulcer
- Male or female patients attending Diabetic Clinics and/or Podiatry Clinics at the hospitals of the New Territories East Cluster
- Aged between 20 and 75 years old inclusive
- All patients should be on stable dose of medication 4 weeks prior to enrolment
- Written informed consent
Key exclusion criteria (13 listed)
- Patients with end-stage renal disease as defined by the need for dialysis or on renal replacement program
- Patients with advanced diabetic eye disease as defined by the history of laser therapy, retinal detachment or vitreous hemorrhage
- Pregnancy, breast feeding, or patient has plans of becoming pregnant during the study period.
- Known allergy to TCM drugs
- Contraindication or intolerance to use of aspirin, statin , ACEI or ARB
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chinese herbal medicine (Radix Rehmanniae and Radix Astragali)2 sachets to be taken daily | Drug | Chinese Herbal Medicine |
| Placebo comparator2 sachets to be taken daily | Drug | Placebo arm |
Primary outcome
Resolution/progression of foot ulcer based on PEDIS
Time frame: 6 months
1 secondary outcome
Hospital admission/attendance/stay
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2011.
- Derived from this study: PubMed 24330156Ko CH, Yi S, Ozaki R, Cochrane H, Chung H, Lau W, Koon CM, Hoi SW, Lo W, Cheng KF, Lau CB, Chan WY, Leung PC, Chan JC. Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with diabetes: a randomized double-blind placebo-controlled study. J Diabetes. 2014 Jul;6(4):323-34. doi: 10.1111/1753-0407.12117. Epub 2014 Feb 24.
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Evaluation of Personalized Nutritional Intervention on Wound Healing of Cutaneous Ulcers in Diabetics
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juliana NA Chan, MBChB, FRCP principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Chinese herbal medicine (Radix Rehmanniae and Radix Astragali) in people with Diabetic Foot Ulcer, run by Chinese University of Hong Kong at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resolution/progression of foot ulcer based on PEDIS (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01389362, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2011.