Clinical Trial of Vit D and Calcium for Recurrent BPPV

Sponsor

Ottawa Hospital Research Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05863949

Collaborator

(none)

860

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Randomized double blind placebo controlled trial of vitamin D supplements, with or without calcium supplementation, versus placebo in reduction of recurrences in BPPV.

Condition or Disease	Intervention/Treatment	Phase
BPPV Benign Paroxysmal Positional Vertigo Vertigo Vertigo, Peripheral Dizziness Dizziness; Epidemic Vitamin D Deficiency Calcium Deficiency	Dietary Supplement: vitamin D +/- calcium Other: Placebo	N/A

Detailed Description

Benign paroxysmal positional vertigo (BPPV) is the most common neuro-otological disorder, with a lifetime prevalence of 2.4 percent.1 BPPV is responsible for nearly one-half of cases of peripheral vestibular dysfunction. It is a highly recurrent disorder, with more than 1 in 4 patients experiencing a second attack, often within 6 months of the first.2-4 According to the Clinical Practice Guidelines for BPPV from the American Academy of Otolaryngology-Head and Neck Surgery Foundation, particle repositioning maneuvers (PRMs) are the only recommended treatment to resolve symptoms for both initial BPPV episodes as well as persistent episodes.5 While attacks can be effectively treated by PRMs, these often must be performed by a physician or other trained healthcare professional, and sometimes multiple attempts are required in order to successfully resolve a patient's symptoms. Furthermore, even with effective particle repositioning, a subset of patients may continue to experience bouts of recurrent attacks, up to several times yearly. The attacks themselves, as well as the nature of their treatment, - especially in patients with recurrent episodes - are prone to lead to interruptions in patients' daily activities, cause sick leaves, and result in significant direct and indirect costs to both the patient and the healthcare system.6 The prevalence of BPPV increases with age and elderly patients with BPPV are more likely to have reduced activities of daily living (ADL) scores, sustain falls, and suffer from depression.4,7 In the United States (US), more than sixty-five percent of patients with BPPV experience potentially avoidable diagnostic testing or therapeutic interventions during the time leading up to a proper diagnosis, costing the US health care system nearly $2 billion per year.5

BPPV is widely accepted to be caused by otoconia that are dislodged from the utricular macula into the semicircular canals - most commonly the posterior canal.8 Otoconia are made of a largely organic core of glycoproteins, with a predominantly inorganic periphery of calcium carbonate.9 Otoconia form within the otherwise low-calcium endolymph via an active, tightly controlled and ordered process.10 Recent studies have shown that the biomineralization of otoconia has similarities to that of bone and teeth, and that bone metabolism has a connection to BPPV. 11-13 Furthermore, an association has been demonstrated between BPPV and osteoporosis, and otoconia formation has been shown to be dysfunctional in animal models of osteoporosis.14,15

The impact of recurrent BPPV on both patients and the healthcare system is multiplicative. With each episode of recurrence, patients become symptomatic - potentially severely so - and must seek treatment again in the form of particle repositioning maneuvers. These patients therefore suffer further functional impairment, potentially missed school and work, and require healthcare interventions which are not without cost to the system. No preventative treatment option for recurrent BPPV exists. Establishing such a preventative treatment would have significant implications in reducing both direct and indirect costs of this highly prevalent and recurrent disorder.

Vitamin D is involved in bodily calcium regulation, and thus poses an attractive potential treatment for BPPV. Vitamin D deficiency is common in many regions worldwide, and supplementation carries little risk. A body of literature has emerged to date investigating potential links between vitamin D deficiency and BPPV - especially recurrent - and whether vitamin D supplementation could in turn serve some role in treatment or prevention.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

860 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is an off-label, multicenter, randomized, clinical trial in vitamin D deficient adults aged 18 and above with recurrent BPPV. Its goal is to determine whether vitamin D supplementation, with or without calcium supplementation, compared with placebo will decrease the frequency of recurrent episodes of BPPV. A total of 860 vitamin D deficient adults diagnosed with recurrent BPPV will be enrolled at participating clinical study sites.This is an off-label, multicenter, randomized, clinical trial in vitamin D deficient adults aged 18 and above with recurrent BPPV. Its goal is to determine whether vitamin D supplementation, with or without calcium supplementation, compared with placebo will decrease the frequency of recurrent episodes of BPPV. A total of 860 vitamin D deficient adults diagnosed with recurrent BPPV will be enrolled at participating clinical study sites.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Enrolled subjects will be blinded to their treatment assignment. Both study staff and trial investigators will be blinded to treatment assignments and will remain blinded throughout the course of the trial. Randomization (treatment assignment) will be performed via computer algorithm based on subject ID. Randomization codes will be maintained in a password protected, encrypted file available only to the single unmasked investigator at each site, in order to prevent accidental unmasking of other trial personnel. All care will be taken to ensure that the study team are kept blinded. Pills, which will be dispensed at 3-month intervals, will be indistinguishable between groups. They will be dispensed in kits that are labeled as outlined in section 6.2 Study Drug Packaging and Labeling.

Primary Purpose:

Treatment

Official Title:

STOP Vertigo: Supplementation of Vitamin D for Termination of Recurrences From Benign Paroxysmal Positional Vertigo

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vitamin D +/- calcium supplementation patients given Vitamin D 1000iu daily. Also given calcium 500mg BID daily if calcium deficient.	Dietary Supplement: vitamin D +/- calcium vitamin D 1000iU daily +/- calcium 500mg BID daily
Placebo Comparator: Placebo arm patients given 3 pills of placebo daily.	Other: Placebo placebo pill x3 daily

Arm

Intervention/Treatment

Experimental: vitamin D +/- calcium supplementation

patients given Vitamin D 1000iu daily. Also given calcium 500mg BID daily if calcium deficient.

Dietary Supplement: vitamin D +/- calcium

vitamin D 1000iU daily +/- calcium 500mg BID daily

Placebo Comparator: Placebo arm

patients given 3 pills of placebo daily.

Other: Placebo

placebo pill x3 daily

Outcome Measures

Primary Outcome Measures

Recurrence rate of BPPV [1 year]
how many recurrences of BPPV

Secondary Outcome Measures

serum vitamin D levels (25(OH)D3) [1 year]
serum vitamin D levels
proportion of serum vitamin D normalization [1 year]
do patients normalize
time to serum vitamin D normalization [1 year]
how long does it take patients to normalize
proportion of recurrences [1 year]
what proportion of total patients have recurrences
duration of recurrences [1 year]
how long do recurrences of BPPV last
EQ-5D [1 year]
quality of life measurement
days per year of missed school/work [1 year]
days per year of missed school/work

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years or older
2 or more distinct episodes of benign paroxysmal positional vertigo within a 12-month period on history
At least 1 episode diagnosed based on physical examination by trained study personnel, meeting the diagnostic criteria of the Bárány Society
Episodes separated in time, with a minimum of 1 week symptom-free between episodes
Serum evidence of Vitamin D deficiency, as evidenced by 25-hydroxy vitamin D level of <75 nmol/L (<30 ng/mL)48
Subject able to provide informed consent to participate in the study

Exclusion Criteria:

Potential subjects will be excluded if they

have another identifiable cause of vertigo identified on history or physical examination
have a history of allergy or medically significant adverse reaction to vitamin D or calcium carbonate
have a chronic medical disorder which is a contraindication to vitamin D or calcium carbonate supplementation, including uncontrolled hyperparathyroidism, nephrolithiasis, or GI malabsorption disorders
are on loop diuretic agents or thiazides
have a contraindication to routine bloodwork for study purposes, including being hospitalized with a critical illness, cellulitis at blood draw sites, or presence of vascular grafts.