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HealthyPhase 2NCT01694537

The Effects of DLBS1033 on Haemostasis Parameters in Healthy Volunteers

A Phase 2 study testing DLBS1033 in people with Healthy, run by Universitas Indonesia at 1 site in Indonesia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
DLBS1033
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
1 siteIndonesia
Study dates
Jul 2012to Dec 2012
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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%

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

Indonesia1 site
  • Indonesia University

    Jakarta, 10430

Other trials in Indonesia

About this study

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.

Read the 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.

Conditions
Healthy
Being tested
DLBS1033, placebo
Keywords
lumbrokinase, fibrinolytic, plasmin-antiplasmin complex, euglobulin clot lysis time, platelet aggregation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DLBS1033Drug

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

  • placeboDrug

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

Study groups in NCT01694537
Study groupRoleWhat they receive
placeboPlacebo comparatorThe 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.
Receives: Drug: DLBS1033; Drug: placebo
DLBS1033ExperimentalThe 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.
Receives: Drug: DLBS1033; Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. plasmin-antiplasmin complex (PAP complex)

    changes in plasmin-antiplasmin complex

    Measured: one week

Secondary outcomes (5)
  1. euglobulin clot lysis time (ECLT)

    changes in euglobulin clot lysis time

    Measured: one week

  2. prothrombin time (PT)

    changes in prothrombin time

    Measured: one week

  3. fibrinogen

    changes in fibrinogen

    Measured: one week

  4. activated partial thromboplastin time (aPTT)

    changes in activated partial thromboplastin time

    Measured: one week

  5. platelet aggregation

    changes in platelet aggregation

    Measured: one week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Sep 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionOct 2012
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01694537
Sponsor's protocol ID
DLBS1033
Status last verified
May 2017
First submitted
7 Sep 2012
Last updated
15 May 2017
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Mihara H, Sumi H, Yoneta T, Mizumoto H, Ikeda R, Seiki M, Maruyama M. A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus. Jpn J Physiol. 1991;41(3):461-72. doi: 10.2170/jjphysiol.41.461.

    PubMed 1960890
  • Kasim M, Kiat AA, Rohman MS, Hanifah Y, Kiat H. Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: a pilot study. J Altern Complement Med. 2009 May;15(5):539-44. doi: 10.1089/acm.2008.0506.

    PubMed 19416019
  • Yan XM, Kim CH, Lee CK, Shin JS, Cho IH, Sohn UD. Intestinal Absorption of Fibrinolytic and Proteolytic Lumbrokinase Extracted from Earthworm, Eisenia andrei. Korean J Physiol Pharmacol. 2010 Apr;14(2):71-5. doi: 10.4196/kjpp.2010.14.2.71. Epub 2010 Apr 30.

    PubMed 20473377
  • Lee CK, Shin JS, Kim BS, Cho IH, Kim YS, Lee EB. Antithrombotic effects by oral administration of novel proteinase fraction from earthworm Eisenia andrei on venous thrombosis model in rats. Arch Pharm Res. 2007 Apr;30(4):475-80. doi: 10.1007/BF02980222.

    PubMed 17489364
  • Kim YS, Pyo MK, Park KM, Hahn BS, Yang KY, Yun-Choi HS. Dose dependency of earthworm powder on antithrombotic and fibrinolytic effects. Arch Pharm Res. 1998 Aug;21(4):374-7. doi: 10.1007/BF02974629.

    PubMed 9875462
  • Schmaier AH, Thornburg CD, Pipe SW. Coagulation and Fibrinolysis. In: McPherson RA, Pincus MR, editor. Henry's Clinical Diagnosis and Management by Laboratory Methods. 21st ed. Philadelphia: Saunders Elsevier; 2007. p. 731-3.

  • Jin L, Jin H, Zhang G, Xu G. Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. Clin Hemorheol Microcirc. 2000;23(2-4):213-8.

    PubMed 11321442
  • Rey I. Pengaruh pemberian lumbrokinase selama 7 hari terhadap status hiperkoagulasi pada penderita ulkus kaki diabetik. Tugas Akhir Dalam Rangka menyelesaikan Pendidikan Dokter Spesialis Ilmu Penyakit Dalam. FK-USU, Medan. 2009.

  • Trisina J, Sunardi F, Suhartono MT, Tjandrawinata RR. DLBS1033, a protein extract from Lumbricus rubellus, possesses antithrombotic and thrombolytic activities. J Biomed Biotechnol. 2011;2011:519652. doi: 10.1155/2011/519652. Epub 2011 Mar 3.

    PubMed 21403877

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DLBS1033 in people with Healthy, run by Universitas Indonesia at 1 site in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

plasmin-antiplasmin complex (PAP complex) (time frame: one week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01694537, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2017.

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