Healthy Clinical Trial
Official title:
The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers
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.
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.
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