The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2012 by Indonesia University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Dexa Medica Group
Information provided by (Responsible Party):
Nafrialdi, Indonesia University
ClinicalTrials.gov Identifier:
NCT01694537
First received: September 7, 2012
Last updated: September 25, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: DLBS1033
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers

Further study details as provided by Indonesia University:

Primary Outcome Measures:
  • plasmin-antiplasmin complex (PAP complex) [ Time Frame: one week ] [ Designated as safety issue: No ]
    changes in plasmin-antiplasmin complex


Secondary Outcome Measures:
  • euglobulin clot lysis time (ECLT) [ Time Frame: one week ] [ Designated as safety issue: No ]
    changes in euglobulin clot lysis time

  • prothrombin time (PT) [ Time Frame: one week ] [ Designated as safety issue: No ]
    changes in prothrombin time

  • fibrinogen [ Time Frame: one week ] [ Designated as safety issue: No ]
    changes in fibrinogen

  • activated partial thromboplastin time (aPTT) [ Time Frame: one week ] [ Designated as safety issue: No ]
    changes in activated partial thromboplastin time

  • platelet aggregation [ Time Frame: one week ] [ Designated as safety issue: No ]
    changes in platelet aggregation


Other Outcome Measures:
  • serum creatinine [ Time Frame: one week ] [ Designated as safety issue: Yes ]
    serum creatinine

  • serum glutamic oxaloacetic transaminase (SGOT) [ Time Frame: one week ] [ Designated as safety issue: Yes ]
    changes in serum glutamic oxaloacetic transaminase

  • serum glutamic pyruvic transaminase (SGPT) [ Time Frame: one week ] [ Designated as safety issue: Yes ]
    changes in serum glutamic pyruvic transminase


Estimated Enrollment: 20
Study Start Date: July 2012
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: DLBS1033
The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction.
Drug: placebo
Placebo is made with same size and shape with study drug.
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.
Drug: DLBS1033
The study drug is enteric coated DLBS1033, which contain 490 mg bioactive protein fraction.
Drug: placebo
Placebo is made with same size and shape with study drug.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01694537

Contacts
Contact: Nafrialdi, MD, PhD, SpPD, SpFK 62-81315873649 nafrialdi@yahoo.com
Contact: Anggi Gayatri, MD 62-816821209 anggig@gmail.com

Locations
Indonesia
Indonesia University Recruiting
Jakarta, Indonesia, 10430
Contact: Nafrialdi , MD, PhD, SpPD, SpFK    62-81315873649    nafrialdi@yahoo.com   
Contact: Anggi Gayatri, MD    62-816821209    anggig@gmail.com   
Principal Investigator: Nafrialdi, MD, PhD, SpPD, SpFK         
Sponsors and Collaborators
Indonesia University
Dexa Medica Group
Investigators
Principal Investigator: Nafrialdi, MD, PhD, SpPD, SpFK Indonesia University
  More Information