The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers
Słowa kluczowe
Abstrakcyjny
Opis
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.
Daktyle
Ostatnia weryfikacja: | 04/30/2017 |
Pierwsze przesłane: | 09/06/2012 |
Szacowana liczba przesłanych rejestracji: | 09/24/2012 |
Wysłany pierwszy: | 09/26/2012 |
Ostatnia aktualizacja przesłana: | 05/10/2017 |
Ostatnia opublikowana aktualizacja: | 05/14/2017 |
Rzeczywista data rozpoczęcia badania: | 06/30/2012 |
Szacowana data zakończenia podstawowej działalności: | 09/30/2012 |
Szacowana data zakończenia badania: | 11/30/2012 |
Stan lub choroba
Interwencja / leczenie
Drug: DLBS1033
Drug: placebo
Faza
Grupy ramion
Ramię | Interwencja / leczenie |
---|---|
Placebo Comparator: placebo 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. | |
Experimental: DLBS1033 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. |
Kryteria kwalifikacji
Wiek kwalifikujący się do nauki | 18 Years Do 18 Years |
Płeć kwalifikująca się do nauki | Male |
Przyjmuje zdrowych wolontariuszy | tak |
Kryteria | 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) |
Wynik
Podstawowe miary wyników
1. plasmin-antiplasmin complex (PAP complex) [one week]
Miary wyników wtórnych
1. euglobulin clot lysis time (ECLT) [one week]
2. prothrombin time (PT) [one week]
3. fibrinogen [one week]
4. activated partial thromboplastin time (aPTT) [one week]
5. platelet aggregation [one week]
Inne miary wyników
1. serum creatinine [one week]
2. serum glutamic oxaloacetic transaminase (SGOT) [one week]
3. serum glutamic pyruvic transaminase (SGPT) [one week]