Herbal Preparation Used as Adjuvant Therapy on Diabetic Ulcers

• Sponsor: Chinese University of Hong Kong (Other)
• Overall Status: Completed
• CT.gov ID: NCT00393510
• Collaborator: (none)
• Enrollment: 80
• Locations: 2
• Arms: 2
• Duration (Months): 63.9
• Patients Per Site: 40
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

Chronic foot ulcers occurring among diabetic patients are difficult to heal. The frequent elderly age with co-morbidities, vascular insufficiencies, peripheral neuropathies and super imposed infections, all contribute towards the chronicity and failure of treatment. Preserving the ulcerated limb is the patients' wish. On the other hand, an infected ulcer that never heals just unnecessarily prolongs suffering. Nevertheless, patients earnestly like to try all methods of healing before accepting amputation.

Objective:To determine whether a course of herbal preparation used as an adjuvant therapy for diabetic patients suffering from chronic foot ulcers may promote healing so that major leg amputation can be avoided.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Foot Ulcer; Amputation	Drug: TCM; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Evidence Base Study on the Clinical Effects of Integrated Western Medicine and Traditional Chinese Medicine for Diabetic Foot Ulcer Treatment
• Study Start Date: Nov 1, 2000
• Actual Primary Completion Date: Mar 1, 2006
• Actual Study Completion Date: Mar 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Traditional Chinese Medicine 12 herbals formulation was given as an adjuvant therapy for the patients orally twice a day.	Drug: TCM; The Decoction is taken orally, twice a day, treatment period is 24 weeks The herbal formulation or a placebo was given as an adjuvant therapy for the treatment of the unhealing ulcers in these diabetic patients. The formula consisted of 12 herbs, viz: Radix astragali, Rhizoma atractylodis marcocephalae, Radix stephaniae tetrandrae, Radix polygoni multiflori, Radix rehmanniae, Radix smilax china, Fructus corni, Rhizoma dioscoreae, Cortex moutan, Rhizoma alismatis, Rhizoma smilacis glabrae, and Fructus schisandrae
Placebo Comparator: Placebo Placebo was made with starch and colouring materials. Given to patient orally twice a day	Drug: Placebo; Placebo taking orally, twice a day, 24 week treatment period The herbal formulation or a placebo was given as an adjuvant therapy for the treatment of the unhealing ulcers in these diabetic patients. The placebo was made with starch and colouring materials.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Limb Salvage [24 weeks]

   The number of successful limb rescued (without amputation).

Secondary Outcome Measures

1. Tumour Necrosis Factor-alpha Levels in Serum [Baseline and 4 week]

   The state of inflammation at baseline and at 4 weeks after treatment. TNF-alpha are in value of serum level.

2. Time of Ulcer Healing [24 week]

   Time taken for maturation of granulation to enable skin grafting.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Well Controlled diabetic state

• Presence of gangrene or non-healing ulcer in diabetic patients over the foot or feet. Infection should be well controlled.

• Good glycaemic control

Exclusion Criteria:

• Pregnant women and women at risk of conception

• Patients taking digitalis glycosides

• Patients with abnormal liver function tests

• Patients with plasma creatinine great then 150 umol/l or unstable renal function

• Poorly controlled Diabetes Mellitus

• Uncontrolled infection

• History of adverse reaction to herbal medicine

• Unstable medical conditions

• Non-compliance with regime

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Orthopaedics & Traumatology, Prince of Wales hospital	Hong Kong		China
2	Department of Orthopaedics and Traumatology, Kwong Wah Hospital	Hong Kong		China

Sponsors and Collaborators

• Chinese University of Hong Kong

Investigators

• Principal Investigator: Leung Ping Chung, MD, Dept. of Orthopaedics & Traumatology, CUHK

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ahlgren SC, Levine JD. Protein kinase C inhibitors decrease hyperalgesia and C-fiber hyperexcitability in the streptozotocin-diabetic rat. J Neurophysiol. 1994 Aug;72(2):684-92.
• Bazan NG, Gordon WC, Marcheselli VL, Lukiw WJ, Duhault J, Koenig-Berard E, Linn DM, DeCoster MA, Mukherjee PK. Experimental models and their use in studies of diabetic retinal microangiopathy. Therapie. 1997 Sep-Oct;52(5):447-51.
• Brodsky JW. Diabetic Foot Surgery of Foot and Ankle. St. louis Mosby 1992, p1361-1467
• Conn, H.M., M.A. and Emmel, V.M. Staining Procedures. Williams and Wilkins Co., Baltimore, 289 pp.m (1960)
• Diemel LT, Brewster WJ, Fernyhough P, Tomlinson DR. Expression of neuropeptides in experimental diabetes; effects of treatment with nerve growth factor or brain-derived neurotrophic factor. Brain Res Mol Brain Res. 1994 Jan;21(1-2):171-5.
• Follansbee MH, Beyer KH Jr, Griffith JW, Vesell ES. Studies on pyrazinoylguanidine. 5. Temporal effects over 24 weeks demonstrating attenuation of diabetic nephropathy in STZ-diabetic rats. Pharmacology. 1997 May;54(5):241-55.
• J.Y.Shi, Collected publications on the applicatioin of Shi's regime for the treatment of diabetic ulcers (in Chinese) special publicaiton on Diabetic Ulcer. Shanghai Research Institute on TCM.
• Kunjathoor VV, Wilson DL, LeBoeuf RC. Increased atherosclerosis in streptozotocin-induced diabetic mice. J Clin Invest. 1996 Apr 1;97(7):1767-73.
• Levin ME. Diabetic foot ulcers: pathogenesis and management. J ET Nurs. 1993 Sep-Oct;20(5):191-8.
• Liu S, Barac-Nieto M. Renal protein degradation in streptozotocin diabetic mice. Diabetes Res Clin Pract. 1997 Jan;34(3):143-8.
• Mavrikakis ME, Sfikakis PP, Kontoyannis D, Horti M, Kittas C, Koutras DA, Raptis SA. Macrovascular disease of coronaries and cerebral arteries in streptozotocin-induced diabetic rats. A controlled, comparative study. Exp Clin Endocrinol Diabetes. 1998;106(1):35-40.
• Nelzén O, Bergqvist D, Lindhagen A. High prevalence of diabetes in chronic leg ulcer patients: a cross-sectional population study. Diabet Med. 1993 May;10(4):345-50.
• Professor P.C. Leung. Limb Salvage for Diabetic ulceration with Traditional Chinese Techniques. Pacific, BioTech News. Vol.1 No.31 1998, Singapore
• Steed DL, Goslen JB, Holloway GA, Malone JM, Bunt TJ, Webster MW. Randomized prospective double-blind trial in healing chronic diabetic foot ulcers. CT-102 activated platelet supernatant, topical versus placebo. Diabetes Care. 1992 Nov;15(11):1598-604.
• Wagner EW. Classification of neuropathic foot problems AAOS instructional lecture 28 St. Louis Mosby 1979 p143-165
• Zochodne DW, Murray MM, van der Sloot P, Riopelle RJ. Distal tibial mononeuropathy in diabetic and nondiabetic rats reared on wire cages: an experimental entrapment neuropathy. Brain Res. 1995 Nov 6;698(1-2):130-6.

• ClinicalTrials.gov Identifier: NCT00393510
• Other Study ID Numbers: CRE-8342
• First Posted: Oct 27, 2006
• Last Update Posted: Jul 13, 2010
• Last Verified: Jul 1, 2010

• Keywords provided by , ,: Diabetic Foot Ulcer; Traditional Chinese Medicine
• Additional relevant MeSH terms: Diabetic Foot; Foot Ulcer; Ulcer

Study Results

Participant Flow

Recruitment Details	Apr 2002 to Apr 2006, Orthopaedic Department, Prince of Wales Hospital, HK Apr 2002 to Apr 2006, Orthopaedic Department, Kwong Wah Hospital, HK
Pre-assignment Detail	Liver Function and Renal Function test normal. Patients suffering from serious cardiac and renal deficiencies were excluded from the study because of safety measure.

Arm/Group Title	Traditional Chinese Medicine	Placebo
Arm/Group Description	12 herbals formulation was given as an adjuvant therapy for the patients orally twice a day.	Placebo was made with starch and colouring materials. Given to patient orally twice a day
Period Title: Overall Study
STARTED	40	40
COMPLETED	37	31
NOT COMPLETED	3	9

Baseline Characteristics

Arm/Group Title	Traditional Chinese Medicine	Placebo	Total
Arm/Group Description	12 herbals formulation was given as an adjuvant therapy for the patients orally twice a day.	Placebo was made with starch and colouring materials. Given to patient orally twice a day	Total of all reporting groups
Overall Participants	40	40	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.3 (12.6)	68.5 (11.1)	67.4 (11.8)
Sex: Female, Male (Count of Participants)
Female	15 37.5%	18 45%	33 41.3%
Male	25 62.5%	22 55%	47 58.8%
Region of Enrollment (participants) [Number]
Hong Kong	40 100%	40 100%	80 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Limb Salvage
Description	The number of successful limb rescued (without amputation).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Traditional Chinese Medicine	Placebo
Arm/Group Description	12 herbals formulation was given as an adjuvant therapy for the patients orally twice a day.	Placebo was made with starch and colouring materials. Given to patient orally twice a day
Measure Participants	40	40
Number [Participants]	37 92.5%	31 77.5%

2. Secondary Outcome

Title	Tumour Necrosis Factor-alpha Levels in Serum
Description	The state of inflammation at baseline and at 4 weeks after treatment. TNF-alpha are in value of serum level.
Time Frame	Baseline and 4 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Traditional Chinese Medicine	Placebo
Arm/Group Description	12 herbals formulation was given as an adjuvant therapy for the patients orally twice a day.	Placebo was made with starch and colouring materials. Given to patient orally twice a day
Measure Participants	40	40
Baseline	48 (116)	44 (83)
Week 4	28 (62)	39 (64)

3. Secondary Outcome

Title	Time of Ulcer Healing
Description	Time taken for maturation of granulation to enable skin grafting.
Time Frame	24 week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Traditional Chinese Medicine	Placebo
Arm/Group Description	12 herbals formulation was given as an adjuvant therapy for the patients orally twice a day.	Placebo was made with starch and colouring materials. Given to patient orally twice a day
Measure Participants	37	31
Mean (Standard Deviation) [Weeks]	5.9 (1.4)	9.2 (1.9)

Adverse Events

Time Frame	24weeks
Adverse Event Reporting Description	During the 24 weeks of treatment, some selflimiting adverse events (epigastric pain, dry month,and diarrhoea) were experienced.
Arm/Group Title	Traditional Chinese Medicine		Placebo
Arm/Group Description	12 herbals formulation was given as an adjuvant therapy for the patients orally twice a day.		Placebo was made with starch and colouring materials. Given to patient orally twice a day
All Cause Mortality
	Traditional Chinese Medicine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Traditional Chinese Medicine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Traditional Chinese Medicine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.