Clinical Trial of Vit D and Calcium for Recurrent BPPV

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

Detailed Description
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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.

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

Conditions
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BPPV, Benign Paroxysmal Positional Vertigo, Vertigo, Vertigo, Peripheral, Dizziness, Dizziness; Epidemic, Vitamin D Deficiency, Calcium Deficiency

Intervention / Treatment
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* Dietary Supplement: vitamin D +/- calcium
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence rate of BPPV | how many recurrences of BPPV | 1 year | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bppv, benign paroxysmal positional vertigo, vertigo, dizziness, vitamin D