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

Universitas Sebelas Maret

Status and phase

Completed

Phase 4

Conditions

Benign Paroxysmal Positional Vertigo (Disorder)

Treatments

Drug: DLBS1033

Drug: Betahistine Mesylate tablet

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT07075289

623/II/HREC/2024

UST-002.24/DLBS1033/1/2024 (Other Grant/Funding Number)

Details and patient eligibility

About

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

Full 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.

Enrollment

44 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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