Effect of the Administration of L-arginine vs. Placebo in Patients Diagnosed With Presbyvestibulopathy.

Study Overview
=================
Brief Summary
-----------------
Presbivestibulopathy is defined as a chronic vestibular syndrome characterized by bilateral vestibulopathy verified with vestibular tests. These tests objectively assess vestibular function: video Head Impulse Test (v-HIT) and Vestibular Caloric Tests. Also, there are some questionnaires that serve us for monitoring and prognosis (Dizziness Handicap Inventory). There is currently no specific treatment for presbyvestibulopathy. The objective of this study is to evaluate the effect of L-arginine vs. placebo on symptoms, changes in the results of vHIT tests of patients diagnosed with presbyvestibulopathy. It will be conducted a randomized, double blind, placebo controled clinical trial. Patients will be men and women who meet the diagnostic criteria for Presbyvestibulopathy of the Barany Society. The sample size will be 12 patients per group. The patients in the experimental group will receive L-arginine at a dose of 3 grams divided into three doses of 1 g (capsules) every 8 hours, for 3 months. Patients in the control group will receive placebo at the same dosage. All patients will receive vestibular rehabilitation exercises. At the beginning and the end of the intervention , the following tests will be carried out: vertigo disability questionnaire, vHIT tests, and the Up and Go time test.

Detailed Description
-----------------
Vertigo is a common cause in the otorhinolaryngology consultation; a high incidence of this condition has been reported, since there are reports indicating that up to 80% of the world population has presented an episode of vertigo at some stage of their lives. In Germany, it has been reported a prevalence of moderate to severe vestibular vertigo is reported, calculated using a representative sample of a 22.9% in adults of 18 to 79 years. In a report of the United States Emergency Department, it has been reported that 3.3% of the first-contact consultations are due to dizziness, of which 32.9% wer of otological or vestibular origin. Vertigo is classified into two categories: vertigo of central origin and peripheral vertigo. Peripheral vertigo, object of study of this investigation, is originated in the vestibular system, located in the inner ear. Among the differential diagnoses of vertigo of peripheral origin we find presbivestibulopathy, which is a condition characterized by bilateral vestibular dysfunction proven with objective diagnostic tests such as video HIT (vHIT), vestibular caloric tests, among others. In addition, the diagnostic must be done in people over 60 years, and other diagnostic criteria established by the diagnostic criteria for Presbyvestibulopathy of the Barany Society. The treatment of vertigo, as well of the presbyvestibulopathy, is aimed to stabilize the pathological fluctuations in peripheral vestibular function, as well as promoting central compensation in case of a permanent deficit in vestibular function. Therefore, the drugs used for its treatment their purpose is to regulate the decompensated vestibular activity and to improve the symptoms, but not to suppress the cause that originates the pathology since the mechanism of action of the disease is not well established. Currently, there is not a first-choice medication for the treatment of vertigo in general, much less for presbyvestibulopathy, since none has show high efficacy and low presence of adverse effects. Some of the drugs used to treat vertigo include anticholinergics, antihistamines, benzodiazepines and calcium channel blockers. In the same way, some substances have been used that have shown effectiveness despite the fact that their mechanism of action is unknown or not very clear, sus as betahistine and Gingko biloba. L-arginine is a precursor amino acid fr the endogenous synthesis of nitric oxide (NO), a molecule produced in the vascular endothelium with vasodilatory, antiatherogenic and antiplatelet action. To date, there is no evidence of the use of L-arginine for the treatment of vertigo, however, its vasodilator effect as a precursor of NO should favor vascular perfusion in the vestibular system, therefore, it is of interest to know the therapeutic effects of L-arginine for ths treatment of pathology.

Official Title
-----------------
Effect of the Administration of L-arginine vs. Placebo on the vHIT Result, Vestibular Caloric Tests and Symptoms of Patients Diagnosed With Presbyvestibulopathy.

Conditions
-----------------
Presbyvestibulopathy

Intervention / Treatment
-----------------
* Drug: L-arginine
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women. Age over 60 years. That patient meets the diagnostic criteria established for presbyvestibulopathy by the Classification Committee of the Barany Society: Chronic vestibular syndrome (al least 3 months duration) with at least 2 of the following symptoms: Postural imbalance or unsteadiness Gait disturbance Chronic dizziness Recurrent falls Mild bilateral peripheral vestibular hypofunction documented by at leat 1 of the following: VOR gain measured by video-HIT between 0.6 and 0.8 bilaterally VOR gain between 0.1 and 0.3 upon sinusoidal stimulation on a rotatory chair (0.1 Hz, Vmax=50-60°/sec) Reduced caloric response (sum of bithermal saccadic peak velocity (SPV) on each side between 6 and 25°/sec) Age ≥60 years Not better accounted for by another disease or disorder Consent under information Exclusion Criteria: Not being able to rule out the use of antivertigo drugs 1 week prior to study entry. Use of vasodilator drugs or antihistamines. Orthostatic hypotension Cognitive deficit of the patient that prevents him from understanding the implications of the study. Known uncontrolled liver or kidney disease. Known hypersensitivity to study drugs. Chronic use of drugs with an anticoagulant effect. Bronchial asthma. Elimination Criteria: Treatment adherence <80% evaluated through registration in an adherence diary and capsules count Presence of serious adverse events Withdrawal of consent under information

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind clinical trial with a placebo control group.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-arginine<br>L-arginine 3 grams per day, divided into doses of 1 g every 8 hours during 90 days. | Drug: L-arginine<br>* L-arginine 2-amino-5-guanidino-pentanoic acid is a proteinogenic amino acid that is a natural constituent of the protein diet.<br>* Other names: Arginine;|
| Placebo Comparator: Placebo<br>Starch 1 gr every 8hr, during 90 days. | Other: Placebo<br>* Starch<br>* Other names: Starch;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Video Head Impulse Test vHIT | The vHIT is a simple, rapid test to assess vestibular function. It is based on the physiological aspects of the vestibular ocular reflex (VOR). VOR is a rapid reflex with a duration of 7 to 10 milliseconds and consists of the ability to keep the gaze fixed on an object with rapid and unexpected movements of the head. This study has a specificity and sensitivity of 100% to evaluate the VOR. | Pre-intervention | 
| Final Video Head Impulse Test vHIT | The vHIT is a simple, rapid test to assess vestibular function. It is based on the physiological aspects of the vestibular ocular reflex (VOR). VOR is a rapid reflex with a duration of 7 to 10 milliseconds and consists of the ability to keep the gaze fixed on an object with rapid and unexpected movements of the head. This study has a specificity and sensitivity of 100% to evaluate the VOR. | Final (after 90 days of intervention) | 
| Baseline Dizziness Handicap Inventory | Questionnaire that helps us to know the degree of emotional, functional and physical disability of patients diagnosed with presbyvestibulopathy. In addition, it has been used by different authors as a prognostic value, to know the improvement of pre- and post-treatment patients. | Pre-intervention | 
| Final Dizziness Handicap Inventory | Questionnaire that helps us to know the degree of emotional, functional and physical disability of patients diagnosed with presbyvestibulopathy. In addition, it has been used by different authors as a prognostic value, to know the improvement of pre- and post-treatment patients. | Final (after 90 days of intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Time up and go Test | It is a simple test that consists of a patient being asked to stand up without support while sitting in a chair without armrests and walk forward for 3 meters and back, the time it takes to do so is timed. Most authors consider that if the duration is greater than 10 seconds, there is a greater risk of falls. | Pre-intervention | 
| Final Time up and go Test | It is a simple test that consists of a patient being asked to stand up without support while sitting in a chair without armrests and walk forward for 3 meters and back, the time it takes to do so is timed. Most authors consider that if the duration is greater than 10 seconds, there is a greater risk of falls. | Final (after 90 days of intervention) | 
| Adverse events | Adverse events will be evaluated through a diary in which patients will record any adverse event presented between visits. Also, it will be verified with direct interview. | Final (after 90 days of intervention) | 
| Initial Audiometry | Audiometry aims to make a graphic record of hearing which is called audiogram. This study help us to detect hearing loss and classiffy it according to its site of origin. | Pre-intervention | 
| Final Audiometry | Audiometry aims to make a graphic record of hearing which is called audiogram. This study help us to detect hearing loss and classiffy it according to its site of origin. | Final (after 90 days of intervention) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
L-arginine, Presbyvestibulopathy, Vertigo, v-HIT