Comparing Oral Lumbrokinase DLBS1033 and Betahistine Mesylate in Benign Paroxysmal Positional Vertigo

NCT ID: NCT07075289

Last Updated: 2025-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-01
• Study Completion Date: 2024-12-27

Brief Summary

The goal of this clinical trial is to learn if oral lumbrokinase DLBS1033 works better than betahistine mesylate on inflammation, quality of life, and dizziness symptoms of adult benign paroxysmal positional vertigo (BPPV) patients. It will also learn about the safety of oral lumbrokinase DLBS1033 as a causative therapy of BPPV. The main questions it aims to answer are:

• Is there a difference in the decrease in IL-1β levels between BPPV patients who receive oral lumbrokinase DLBS1033 therapy and patients who receive betahistine mesylate therapy?
• Is there a difference in the decrease in TNF-α levels between BPPV patients who receive oral lumbrokinase DLBS1033 therapy and patients who receive betahistine mesylate therapy?
• Is there a difference in the decrease in VCAM-1 levels between BPPV patients who receive oral lumbrokinase DLBS1033 therapy and patients who receive betahistine mesylate therapy?
• Is there a difference in the quality of life between BPPV patients who receive oral lumbrokinase DLBS1033 therapy and patients who receive betahistine mesylate therapy?
• Is there a difference in the time to improve dizziness symptoms between BPPV patients who receive oral lumbrokinase DLBS1033 therapy and patients who receive betahistine mesylate therapy? Researchers will compare oral lumbrokinase DLBS1033 to betahistine mesylate to see if oral lumbrokinase DLBS1033 works better to treat BPPV

Participants will:

• Join a brief interview to find out the current and past medical history, as well as a physical examination of the study participants
• Give blood samples for biomarker examination, which will be conducted at the Clinical Pathology Laboratory of Dr. Moewardi Surakarta Hospital
• Take oral lumbrokinase DLBS1033 or betahistine mesylate every day for 2 weeks
• Visit the clinic once every week for evaluation and the blood test
• Keep a diary of their symptoms

Detailed Description

This study was designed as a randomized controlled double-masked trial, representing a robust experimental approach to compare the therapeutic effects of oral lumbrokinase DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica b.i.d.) and betahistine mesylate (12 mg, MERTIGO SR tablet, Dexa Medica b.i.d.) in patients suffering from BPPV for a 14-day prospective observation period. The research was carried out at the Neurology Outpatient Clinic of Dr. Moewardi General Hospital in Surakarta, Central Java, Indonesia, between April and August 2024, following full ethical approval from the hospital's Health Research Ethics Committee.

The study population comprised patients attending the aforementioned clinic, with specific inclusion and exclusion criteria applied to select eligible subjects via a purposive sampling method. Included patients were between 18 and 65 years old, diagnosed with BPPV by a neurologist based on a clear history of positional vertigo symptoms (nausea, vomiting, imbalance with head movements) and characteristic torsional nystagmus during the Dix-Hallpike maneuver (latency, fatigability, duration less than 60 seconds). Furthermore, participants had to be proficient in Indonesian and provide informed consent. Patients were excluded if they were pregnant or breastfeeding, showed signs of central vertigo or other neurological deficits, had current ear infections, hearing impairment, tinnitus, head trauma, or underlying conditions such as thyroid disorders, diabetes mellitus, osteoarthritis, a history of neoplasm, cardiovascular disease, hypertension, or recent ear/mastoid surgery. Cognitive impairment and participation in other clinical trials within 30 days prior to screening were also grounds for exclusion. To ensure data integrity, dropout criteria were established for patients unable to complete the study protocol, those who did not adhere to procedures, or those failing to complete the necessary questionnaires.

A total of 44 participants were enrolled, determined by a sample size calculation based on a 95% confidence interval and 5% confidence limits, with an additional 10% allowance for potential dropouts from a previous year's patient population of 751 peripheral vertigo cases. Standardized instruments were utilized for data collection, including the Indonesian version of Dizziness Handicap Inventory (DHI) for assessing quality of life which categorize it as poor, moderate, or good based on physical, emotional, and functional aspects; and the Indonesian version of the Vertigo Symptom Scale-Short Form (VSS-SF) to evaluate dizziness symptom severity, which is categorized as severe or low [15]. Furthermore, concentrations of key inflammatory biomarkers, specifically TNF-α, IL-1β, and VCAM-1, were quantified using Human Quantikine R&D Systems kits on a Thermo Fisher Invitrogen auto-analyzer according to manufacturer specifications.

The study protocol involved a two-block randomization to ensure balanced group assignments. The random sequences for the group allocation were generated by independent personnel of the direct study management and kept in sealed envelopes. This allocation concealment ensured that neither the investigator team nor the participants knew their assigned treatment. Each package was coded with the subject identification number according to the generated random number and assigned to each eligible subject. These codes remained unrevealed until the study's completion. The investigator team members, assigned as the enumerators, conducted symptom and quality of life assessments using the DHI and VSS-SF on the first day (baseline), seventh day, and fourteenth day after treatment initiation. Concurrently, blood samples were collected to assess TNF-α, IL-1β, and VCAM-1 levels. All collected data were then compiled and statistically analyzed using SPSS for Windows 25.0. Before hypothesis testing, data completeness and accuracy were verified, followed by coding, tabulation, and entry into the software. Normality of data distribution was assessed using the Kolmogorov-Smirnov test. Independent T-tests were performed for normally distributed data. Multiple linear regression analysis was conducted to investigate the relationship between inflammatory markers, quality of life, and potential confounding variables, and ordinal logistic regression analysis was conducted to determine the odds ratios (ORs) for inflammation levels and quality of life.

Conditions

Benign Paroxysmal Positional Vertigo (Disorder)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Oral lumbrokinase DLBS1033 group

BPPV patients who got oral lumbrokinase DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica b.i.d.) for 14-day prospective observation period.

Group Type: EXPERIMENTAL

DLBS1033

Intervention Type: DRUG

Participants would get oral lumbrokinase DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica b.i.d.) for a 14-day prospective observation period.

Betahistine mesylate group

BPPV patients who got betahistine mesylate (12 mg, MERTIGO SR tablet, Dexa Medica b.i.d.) for 14-day prospective observation period.

Group Type: ACTIVE_COMPARATOR

Betahistine Mesylate tablet

Intervention Type: DRUG

Patients would get betahistine mesylate (12 mg, MERTIGO SR tablet, Dexa Medica b.i.d.) for a 14-day prospective observation period.

Interventions

DLBS1033

Participants would get oral lumbrokinase DLBS1033 (490 mg, DISOLF film-coated tablet, Dexa Medica b.i.d.) for a 14-day prospective observation period.

Intervention Type: DRUG

Betahistine Mesylate tablet

Patients would get betahistine mesylate (12 mg, MERTIGO SR tablet, Dexa Medica b.i.d.) for a 14-day prospective observation period.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Aged between 18 and 65 years old
• Diagnosed with BPPV by a neurologist based on a clear history of positional vertigo symptoms (nausea, vomiting, imbalance with head movements) and characteristic torsional nystagmus during the Dix-Hallpike maneuver (latency, fatigability, duration less than 60 seconds)
• Proficient in Indonesian
• Provided informed consent

Exclusion Criteria

• Pregnant or breastfeeding
• Showed signs of central vertigo or other neurological deficits
• Had current ear infections, hearing impairment, tinnitus, head trauma, or underlying conditions such as thyroid disorders, diabetes mellitus, osteoarthritis, a history of neoplasm, cardiovascular disease, hypertension, or recent ear/mastoid surgery.
• Cognitive impairment
• Participation in other clinical trials within 30 days prior to screening

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dexa Medica Group

INDUSTRY

Sponsor Role: collaborator

Universitas Sebelas Maret

OTHER

Sponsor Role: lead

Responsible Party

Stefanus Erdana Putra

Medical Doctor (Neurologist)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stefanus E Putra, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Faculty of Medicine, Universitas Sebelas Maret

Locations

Dr. Moewardi Regional General Hospital

Surakarta, Central Java, Indonesia

Countries

Indonesia

References

Walther LE, Wenzel A, Buder J, Bloching MB, Kniep R, Blodow A. Detection of human utricular otoconia degeneration in vital specimen and implications for benign paroxysmal positional vertigo. Eur Arch Otorhinolaryngol. 2014 Dec;271(12):3133-8. doi: 10.1007/s00405-013-2784-6. Epub 2013 Oct 30.

Reference Type: BACKGROUND

PMID: 24170182 (View on PubMed)

Tang Y, Zhou X, Cao T, Chen E, Li Y, Lei W, Hu Y, He B, Liu S. Endoplasmic Reticulum Stress and Oxidative Stress in Inflammatory Diseases. DNA Cell Biol. 2022 Nov;41(11):924-934. doi: 10.1089/dna.2022.0353. Epub 2022 Sep 14.

Reference Type: BACKGROUND

PMID: 36356165 (View on PubMed)

Bashiruddin J, Alviandi W, Branantyo B, Daneswarry D. 2019. Validitas, reliabilitas dan adaptasi transkultural Dizziness Handicap Inventory dalam bahasa Indonesia. Oto Rhino Laryngologica Indonesiana. 49(2), 162-3. https://doi.org/10.32637/orli.v49i20.318.

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

https://perpustakaan.rsmoewardi.com/index.php?p=show_detail&id=1557

Study protocol

Other Identifiers

UST-002.24/DLBS1033/1/2024

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

623/II/HREC/2024

Identifier Type: -

Identifier Source: org_study_id