Effect of Herbal Products on Platelet Function and Clotting

A Randomized, Double Blind, Placebo-controlled Crossover Study on the Effect of Commonly Used Herbal Products on Platelet Function and Coagulation Profile of Healthy Volunteers

This is a research study on the effect of some commonly used "blood activating" herbal products on platelet function and coagulation profile, ie whether it causes an increase in bleeding tendency, either used alone or in combination with Aspirin which is a commonly used anti-platelet drug.

Study Overview

• Status: Completed
• Conditions: Platelet Function Test
• Intervention / Treatment: Drug: Angelica sinensis; Drug: Aspirin; Drug: Curcuma longa; Drug: Siwu Tang

Detailed Description

This study is being conducted because there has not been any proper studies to provide evidence that these commonly used "blood activating" herbal preparations can in fact affect blood clotting by interfering with platelet function or clotting mechanism and potentiate the antiplatelet activity of Aspirin. These are assumptions based on TCM theory, laboratory experiments and animal studies but have led to the general statement in medical literature that these herbs increases bleeding risk in patients taking Aspirin or any other anti-platelet drugs. This has resulted in advice that these herbal products should not be taken by patients on Aspirin, which is a common drug taken by many patients. We hope to prove or disprove this theoretical concern by measurement of platelet and clotting function in healthy volunteers before and after taking the herbal product, alone and in combination with Aspirin. This will help to answer the question of whether it is safe for patients to take these common "blood -activating " herbs alone or together with Aspirin.

Healthy volunteers will be consecutively enrolled into 3 arms, each studying one herbal product for 25 volunteers. The design involves taking all 3 of the following combinations: aspirin + placebo, herb + placebo, aspirin + herb, each for a 3-week period, in a randomized order, with 2 weeks of wash-out in between each 3-week period. Platelet function and coagulation profile will be assayed

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169856
    • Singapore General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and females between the ages of 18 and 70 years.
2. Healthy by medical history and physical exam.
3. Laboratory values within established guidelines for participation in clinical studies: AST less than or equal to 2 times the ULN; SCr less than or equal to ULN; FBC showing normal Hb; WBC and platelet count; normal aPTT/PT
4. Negative urine pregnancy test for females of child-bearing potential.
5. Females of child-bearing potential who are able and willing to practice abstinence or use non-hormonal effective methods of birth control during the study, such as condoms or diaphragms.

Exclusion Criteria:

1. Concomitant therapy (chronic or intermittent) with herbal drugs, aspirin, any other anti-platelet agents, non-steroidal anti-inflammatory medications or warfarin from 14 days prior to study participation and throughout the study period
2. Inability to obtain venous access for blood sample collection.

3. The presence of any of the following significant medical conditions:

   1. Diabetes mellitus poorly controlled or requiring insulin
   2. Hypertension poorly controlled
   3. Cardiac disease : heart failure, arrhythmia poorly controlled
   4. Renal disease,
   5. Hepatic impairment
   6. Bleeding disorders including thrombocytopenia and coagulopathy, either congenital or acquired
   7. Peptic ulcer disease
   8. Psychiatric illnesses that may interfere with the subject's ability to participate in the study, or any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigators.
4. Plans for elective surgery during the investigation or within 2 weeks following completion of the study.
5. Positive urine pregnancy test or breastfeeding female.
6. The presence of persistent diarrhea or malabsorption that would interfere with the subject's ability to absorb drugs.
7. Drug or alcohol abuse that may impair safety or adherence (more than 3 alcoholic drinks per day, on a daily basis).
8. History of intolerance or allergic reaction to aspirin or any NSAIDS
9. Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Angelica sinensis; Angelica sinensis in capsule form will be given with actual or placebo aspirin, each for a 3 week period. Clotting profile and platelet function test will be done before and after.	Drug: Angelica sinensis; Angelicae sinensis in capsule form will be given with actual or placebo aspirin, each for a 3 week period. Clotting profile and platelet function test will be done before and after.; Drug: Aspirin; Aspirin (enteric-coated) at 100mg daily will be given one of the actual herb or placebo herb, each for a 3 week period. Clotting profile and platelet function test will be done before and after.
Active Comparator: Curcuma longa; Curcuma longa in capsule form will be given with actual or placebo aspirin, each for a 3 week period. Clotting profile and platelet function test will be done before and after.	Drug: Aspirin; Aspirin (enteric-coated) at 100mg daily will be given one of the actual herb or placebo herb, each for a 3 week period. Clotting profile and platelet function test will be done before and after.; Drug: Curcuma longa; Curcuma longa in capsule form will be given with actual or placebo aspirin, each for a 3 week period. Clotting profile and platelet function test will be done before and after.
Active Comparator: Siwu Tang; TCM formulation "Siwu Tang" consisting of 4 herbs ( Ligustici chuangxiong, Angelicae sinensis, Rehmanniae praeparata and Paeoniae alba) in tablet form will be given with actual or placebo aspirin, each for a 3 week period. Clotting profile and platelet function test will be done before and after.	Drug: Aspirin; Aspirin (enteric-coated) at 100mg daily will be given one of the actual herb or placebo herb, each for a 3 week period. Clotting profile and platelet function test will be done before and after.; Drug: Siwu Tang; TCM formulation "Siwu Tang" consisting of 4 herbs ( Ligustici chuangxiong, Angelicae sinensis, Rehmanniae praeparata and Paeoniae alba) in tablet form will be given with actual or placebo aspirin, each for a 3 week period. Clotting profile and platelet function test will be done before and after.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
platelet function test and coagulation profile	Platelet function test and coagulation profile ( aPTT/PT) will be done at baseline and after each phase of 3 weeks of Herb/aspirin or their placebo	3 weeks

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Collaborators: Singhealth Foundation

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: December 8, 2013
• First Submitted That Met QC Criteria: December 8, 2013
• First Posted (Estimate): December 11, 2013

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 18, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Protective Agents; Antioxidants; Aspirin; Turmeric extract
• Other Study ID Numbers: TCM platelet function