The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers

The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers

Sponsors

Lead Sponsor: Indonesia University

Collaborator: Dexa Medica Group

Source Indonesia University
Brief Summary

DLBS1033 is bioactive protein fraction which extracted from Lumbricus rubellus earthworm. This earthworm comes from Pengalengan, West Java, Indonesia. DLBS1033 possesses 8 major proteins with molecular weight below 100 kDa, so its named as Lumbricus Low Molecular weight Proteins (LLP). This enzym can be transported to the bloodstream via intestinal epitel. Structure of DLBS1033 looks like lumbrokinase. Lumbrokinase is enzym that consist of 6 isoenzyme serine protease. As a drug that consists of serin protease enzym, suspected that the mechanism of action of DLBS1033 similar with lumbrokinase, especially as plasminogen activator in fibrinolytic system. In vitro study by Trisina et al showed that DLBS1033 has fibrinogenolytic activities on fibrinogen α, beta, and gamma chain, decreasing platelet aggregation and clotting time was prolonged. Until now, the mechanism of action and effects of DLBS1033 on human fibrinolytic and coagulation system still unknown. Therefore, the aim of this clinical trial is to evaluate the effects of DLBS1033 on human fibrinolytic and coagulation system on healthy subjects.

Detailed Description

Fibrinolysis is a process to lyse clot formed by thrombin. It starts with activating plasminogen to plasmin by the endogenous tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA). These activator are found in the endothelium, granulocytes and monocytes. Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of tPA and uPA) and α2-antiplasmin is major inhibitor of plasmin. Plasmin wil degrade soluble fibrinogen and fibrin to produce fibrinogen degradation products and fibrin degradation products, respectively. Lumbrokinase has been investigated in animal studies. Kim et al was conducting on rats by administered freeze-dried powder of Lumbricus rubellus earthworm orally. This study showed that earthworm powder is valuable for the prevention and/or treatment of thrombotic conditions. Similar conclusion also shown on study by Lee et al, which compared antithrombotic and fibrinolytic activities of lumbrokinase SPP-501 (extracted from Eisenia andrei earthworm) with urokinase and t-PA in a thrombosis model of rat vena. The results of this study were decreasing of thrombus weight, shortening of euglobulin lysis time (ELT), and reducing platelet aggregation of rat which given SPP-501. Conclusion from several clinical trial similar with several studies on animal. From study which was conducted by Jin et al on 51 cerebral infarct subjects which were given 3 times 400 mg lumbrokinase (n = 31) or control (n = 20) for 28 days. In the treatment group, kaolin partial thromboplastin time (KPTT) was prolonged, t-PA activity and D-dimer level increase, and fibrinogen decreased significantly. It is concluded that mechanism of lumbrokinase as oral antithrombotic and fibrinolytic are by inhibition of coagulation intrinsic pathway and activate fibrinolytic pathway by increasing t-PA activity. Fibrinolytic activity was also concluded by Rey, who was conducted study on 28 diabetic foot ulcer subjects, which were given 3 times 500 mg lumbrokinase per day (n = 14) for 7 days, or placebo. On this study, in the treatment group mean of D-dimer was increased. From many clinical trials, it is concluded that effects of lumbrokinase have seen after several days. It is different with intravenous fibrinolytic enzym, such as streptokinase and t-PA, which effects have seen soon after it was used. Therefore oral lumbrokinase could not replace the function of intravenous fibrinolytic enzym,that was used on acute thrombosis. Based on antithrombotic and fibrinolytic activity, lumbrokinase might used as secondary prevention after acute thrombosis, such as myocard infarct and stroke. Some researchers have started clinical trials about that hypothesis. Pilot study by Kasim et al was used a lumbrokinase in 10 patient with stable angina pectoris. This study showed that 70% of total sample receiving lumbrokinase had a significant decrease in summed stress score of perfusion imaging and better perfusion in viable myocardium after 30 days of lumbrokinase treatment.

Overall Status Completed
Start Date 2012-07-01
Completion Date 2012-12-01
Primary Completion Date 2012-10-01
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
plasmin-antiplasmin complex (PAP complex) one week
Secondary Outcome
Measure Time Frame
euglobulin clot lysis time (ECLT) one week
prothrombin time (PT) one week
fibrinogen one week
activated partial thromboplastin time (aPTT) one week
platelet aggregation one week
Enrollment 21
Condition
Intervention

Intervention Type: Drug

Intervention Name: DLBS1033

Description: The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction.

Intervention Type: Drug

Intervention Name: placebo

Description: Placebo is made with same size and shape with study drug.

Eligibility

Criteria:

Inclusion Criteria: - Male - 18-55 years old - body mass index between 18-25 kg/square metres - normal physical examination - Patient still have the ability to undergo examinations and give written informed consent - Plasmin-antiplasmin complex (PAP complex) level between 0-514 ng/ml - Platelet aggregation (ADP 10 uM) > 49% Exclusion Criteria: - Patient with cardiovascular disease, hypertension, diabetes mellitus, and dyslipidemia - Creatinin serum more than 1,5 x upper limit normal - SGOT and SGPT more than 3 x upper limit normal - Blood pressure ≥ 140/90 mmHg - Fasting blood glucose > 126 mg/dL - Alcohol patients - Took any medications (including traditional medicine, supplement and vitamin) in 1 week before the study) - Patient has bleeding history which unclear etiology - Hemoglobin < 10 g/dL - Thrombocyte count < 100.000/uL - Heavy smoker (Bringman Index > 600)

Gender:

Male

Minimum Age:

18 Years

Maximum Age:

55 Years

Healthy Volunteers:

Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Nafrialdi, MD, PhD, SpPD, SpFK Principal Investigator Indonesia University
Overall Contact Contact information is only displayed when the study is recruiting subjects.
Location
Facility: Indonesia University
Location Countries

Indonesia

Verification Date

2017-05-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Indonesia University

Investigator Full Name: Nafrialdi

Investigator Title: MD, PhD, SpPD, SpFK

Keywords
Has Expanded Access No
Number Of Arms 2
Arm Group

Label: placebo

Type: Placebo Comparator

Description: The comparison drug is placebo, which is made with same size and shape with study drug. DLBS1033 and placebo is produced by PT Dexa Medica. Placebo will taken 3 times 1 tablet per day for 7 days. Wash out period before enter another arm is 7 days.

Label: DLBS1033

Type: Experimental

Description: The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction. The drug will taken 3 times 490 mg per day for 7 days. Wash out period before enter another arm is 7 days.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

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