NCT01694537

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for phase_2 healthy

Timeline
Completed

Started Jul 2012

Shorter than P25 for phase_2 healthy

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2012

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 7, 2012

Completed
20 days until next milestone

First Posted

Study publicly available on registry

September 27, 2012

Completed
4 days until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2012

Completed
Last Updated

May 15, 2017

Status Verified

May 1, 2017

Enrollment Period

3 months

First QC Date

September 7, 2012

Last Update Submit

May 11, 2017

Conditions

Healthy

Keywords

lumbrokinasefibrinolyticplasmin-antiplasmin complexeuglobulin clot lysis timeplatelet aggregation

Outcome Measures

Primary Outcomes (1)

  • plasmin-antiplasmin complex (PAP complex)

    changes in plasmin-antiplasmin complex

    one week

Secondary Outcomes (5)

  • 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

Other Outcomes (3)

  • serum creatinine

    one week

  • serum glutamic oxaloacetic transaminase (SGOT)

    one week

  • serum glutamic pyruvic transaminase (SGPT)

    one week

Study Arms (2)

placebo

PLACEBO COMPARATOR

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: DLBS1033Drug: placebo

DLBS1033

EXPERIMENTAL

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: DLBS1033Drug: placebo

Interventions

DLBS1033DRUG

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

DLBS1033placebo
placeboDRUG

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

DLBS1033placebo

Eligibility Criteria

Age18 Years - 55 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Male
  • 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%

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Indonesia University

Jakarta, 10430, Indonesia

Location

Related Publications (9)

  • 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.

    PMID: 1960890BACKGROUND

  • 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.

    PMID: 19416019BACKGROUND

  • 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.

    PMID: 20473377BACKGROUND

  • 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.

    PMID: 17489364RESULT

  • 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.

    PMID: 9875462RESULT

  • 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.

    RESULT

  • 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.

    PMID: 11321442RESULT

  • 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.

    RESULT

  • 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.

    PMID: 21403877RESULT

MeSH Terms

Interventions

DLBS 1033

Study Officials

  • Nafrialdi, MD, PhD, SpPD, SpFK

    Indonesia University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD, PhD, SpPD, SpFK

Study Record Dates

First Submitted

September 7, 2012

First Posted

September 27, 2012

Study Start

July 1, 2012

Primary Completion

October 1, 2012

Study Completion

December 1, 2012

Last Updated

May 15, 2017

Record last verified: 2017-05

Data Sharing

IPD Sharing
Will not share

Locations

ID(1)