Novel Treatment of Intermittent Claudication in Patients With Peripheral Arterial Disease Using Danshen Gegen (D&G) Capsule

NCT02380794 | Completed Phase 2 DMC

• 1 other identifier: DG-PAD
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

Peripheral arterial disease (PAD) due to lower limb arterial blockages affects significant proportion of the population with an age-adjusted prevalence of approximately 12%. Claudication induced walking impairment can be debilitating and adversely affects social, leisure, and occupational activities in many patients and is associated with higher mortality among PAD patients. Unfortunately, very few effective therapies are available to improve leg symptoms and exercise performance in PAD patients. Surgery is the last resort but results vary. Therefore, there is a large unmet need for medical therapies that can improve long-term walking performance and functional capacity in PAD patients. Danshen and Gegen (D\&G) are commonly used Chinese herbal medicine in the treatment of cardiovascular diseases. D\&G study has been extensively researched and continued at The Chinese University of Hong Kong (CUHK) for their antioxidative and vasodilator properties, modulate anti-atherosclerosis and improve arthrogenic athophysiology. Three randomized trials were completed at the CUHK showing D\&G improved lipid profile, vascular function and thinned down the internal layer of the carotid artery. One may expect the same with lower limb arteries. Extensive clinical experiences of use in China and Hong Kong indicated that D\&G are well tolerated and safe. This project is a randomized control trial to determine the efficacy and Safety of D\&G in improving the functional capacity \& QoL in patients with symptomatic PAD. The results of this study have the potential to change local and international practice in providing a much needed therapeutic option in the treatment of PAD.

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Keywords

Danshen Gegen Capsule

Outcome Measures

Primary Outcomes (1)

• Change in total distance walked on a standardized graded treadmill

  between baseline and 24 weeks

Secondary Outcomes (6)

• Change in distance walked to onset of claudication

  between baseline and 24 weeks

• Change in health related quality of life assessed by EuroQol-5 Dimension

  between baseline and 24 weeks

• Change in functional status assessed by Walking Impairment Questionnaire

  between baseline and 24 weeks

• Rates of combined cardiovascular events including vascular death, myocardial infarction, stroke, revascularization, or readmission to hospital for a vascular or atherosclerosis-related complication

  At 24 weeks

• Change in ankle brachial index before and after exercise by brachial-to-ankle pulse wave velocity

  between baseline and 24 weeks

Study Arms (2)

Danshen Gegen Capsule

ACTIVE COMPARATOR

3 capsules (500 mg per capsule) twice daily for 24 weeks

Drug: Danshen Gegen Capsule

Placebo

PLACEBO COMPARATOR

3 capsules (500 mg per capsule) twice daily for 24 weeks

Drug: Placebo

Interventions

Danshen Gegen Capsule DRUG

Danshen can dilate blood vessels, reduce the number of angina attacks and significantly improve endothelial function in patients with Coronary Angina Pectoris. Gegen is also effective in dilating cardiovascular and cerebrovascular of the brain, and improving blood circulation. The main active ingredient of Gegen isoflavones is effective in dilating the coronary arteries, improving metabolism in normal and ischemic myocardium and reducing blood pressure, heart rate and myocardial oxygen consumption.

Also known as: D&G

Danshen Gegen Capsule

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women 40 years or older
• With stable intermittent claudication secondary to PAD defined as resting ABI \<0.90 and a ≥10mmHg decrease in ankle artery blood pressure after exercise.
• No change in existing therapy for claudication within 3 months of study enrollment.

You may not qualify if:

• Critical limb ischemia defined by ischemic rest pain, ulceration, or gangrene
• Major lower limb amputation
• Surgical or endovascular revascularization for PAD within 3 months prior to enrolment
• Exercise limitation due to significant concomitant disease (e.g. severe arthritis, cardiac or pulmonary disease)
• Pregnant women and women who are breastfeeding
• Patients who are currently on Warfarin
• Patients with resting systolic blood pressure below 100mmHg (SBP \< 100mmHg)

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

Related Publications (8)

• Criqui MH, Fronek A, Barrett-Connor E, Klauber MR, Gabriel S, Goodman D. The prevalence of peripheral arterial disease in a defined population. Circulation. 1985 Mar;71(3):510-5. doi: 10.1161/01.cir.71.3.510.

  PMID: 3156006 BACKGROUND

• Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: the Framingham Study. J Am Geriatr Soc. 1985 Jan;33(1):13-8. doi: 10.1111/j.1532-5415.1985.tb02853.x.

  PMID: 3965550 BACKGROUND

• McDermott MM, Greenland P, Liu K, Guralnik JM, Celic L, Criqui MH, Chan C, Martin GJ, Schneider J, Pearce WH, Taylor LM, Clark E. The ankle brachial index is associated with leg function and physical activity: the Walking and Leg Circulation Study. Ann Intern Med. 2002 Jun 18;136(12):873-83. doi: 10.7326/0003-4819-136-12-200206180-00008.

  PMID: 12069561 BACKGROUND

• McDermott MM, Liu K, Greenland P, Guralnik JM, Criqui MH, Chan C, Pearce WH, Schneider JR, Ferrucci L, Celic L, Taylor LM, Vonesh E, Martin GJ, Clark E. Functional decline in peripheral arterial disease: associations with the ankle brachial index and leg symptoms. JAMA. 2004 Jul 28;292(4):453-61. doi: 10.1001/jama.292.4.453.

  PMID: 15280343 BACKGROUND

• Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation. 2006 Mar 21;113(11):e463-654. doi: 10.1161/CIRCULATIONAHA.106.174526. No abstract available.

  PMID: 16549646 BACKGROUND

• Chan YL, Woo KS, Leung PC, Fung KP. Traditional Chinese medicine Danshen-Gegen combination formula improves atherogenic pathophysiology: an in-vitro and ex-vivo study. Journal of the Hong Kong College of Cardiology. 2006;14:28.

  BACKGROUND

• Tam LWY, Chook, P, Poon PYK, Qiao M, Chan LLT, Cheung ASP, Chan TYK,Fung KP, Tang KSL, Lau VKM, Koon JCM, Leung PC, Celemajer DS, Woo KS. Danshen and Gegen as cardiovascular tonic in coronary patients: a novel strategy for secondary atherosclerosis prevention. Journal of the Hong Kong College of Cardiology. 2004;12:32.

  BACKGROUND

• McDermott MM, Greenland P, Liu K, Guralnik JM, Criqui MH, Dolan NC, Chan C, Celic L, Pearce WH, Schneider JR, Sharma L, Clark E, Gibson D, Martin GJ. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA. 2001 Oct 3;286(13):1599-606. doi: 10.1001/jama.286.13.1599.

  PMID: 11585483 BACKGROUND

MeSH Terms

Conditions

Peripheral Arterial Disease; Intermittent Claudication

Interventions

Danshen-Gegen

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Bryan Ping Yen YAN

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated Professor

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: March 5, 2015
• Study Start: October 28, 2015
• Primary Completion: June 2, 2017
• Study Completion: June 2, 2017
• Last Updated: July 29, 2019

Record last verified: 2019-07

Locations

HK (1)