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

NCT05932979 | Withdrawn Phase 2 DMC

• 1 other identifier: 160/22
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Presbyvestibulopathy

Keywords

L-arginine; Presbyvestibulopathy; Vertigo; v-HIT

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Baseline Time up and go Test

  Pre-intervention

• Final Time up and go Test

  Final (after 90 days of intervention)

• Adverse events

  Final (after 90 days of intervention)

• Initial Audiometry

  Pre-intervention

• Final Audiometry

  Final (after 90 days of intervention)

Study Arms (2)

L-arginine

EXPERIMENTAL

L-arginine 3 grams per day, divided into doses of 1 g every 8 hours during 90 days.

Drug: L-arginine

Placebo

PLACEBO COMPARATOR

Starch 1 gr every 8hr, during 90 days.

Other: Placebo

Interventions

L-arginine DRUG

L-arginine 2-amino-5-guanidino-pentanoic acid is a proteinogenic amino acid that is a natural constituent of the protein diet.

Also known as: Arginine

L-arginine

Placebo OTHER

Starch

Also known as: Starch

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centro Universitario de Tonalá: lead

Study Sites (1)

CUTonalá

Tonalá, Jalisco, 45425, Mexico

Location

Related Publications (10)

• Agrawal Y, Van de Berg R, Wuyts F, Walther L, Magnusson M, Oh E, Sharpe M, Strupp M. Presbyvestibulopathy: Diagnostic criteria Consensus document of the classification committee of the Barany Society. J Vestib Res. 2019;29(4):161-170. doi: 10.3233/VES-190672.

  PMID: 31306146 BACKGROUND

• Aggarwal NT, Bennett DA, Bienias JL, Mendes de Leon CF, Morris MC, Evans DA. The prevalence of dizziness and its association with functional disability in a biracial community population. J Gerontol A Biol Sci Med Sci. 2000 May;55(5):M288-92. doi: 10.1093/gerona/55.5.m288.

  PMID: 10819319 BACKGROUND

• Alrwaily M, Whitney SL. Vestibular rehabilitation of older adults with dizziness. Otolaryngol Clin North Am. 2011 Apr;44(2):473-96, x. doi: 10.1016/j.otc.2011.01.015.

  PMID: 21474018 BACKGROUND

• Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R. Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2009 Jan;89(1):77-84. doi: 10.3945/ajcn.2008.26544. Epub 2008 Dec 3.

  PMID: 19056561 BACKGROUND

• Rodrigues DL, Ledesma ALL, Pires de Oliveira CA, Bahmad F Jr. Effect of Vestibular Exercises Associated With Repositioning Maneuvers in Patients With Benign Paroxysmal Positional Vertigo: A Randomized Controlled Clinical Trial. Otol Neurotol. 2019 Sep;40(8):e824-e829. doi: 10.1097/MAO.0000000000002324.

  PMID: 31356483 BACKGROUND

• Dong JY, Qin LQ, Zhang Z, Zhao Y, Wang J, Arigoni F, Zhang W. Effect of oral L-arginine supplementation on blood pressure: a meta-analysis of randomized, double-blind, placebo-controlled trials. Am Heart J. 2011 Dec;162(6):959-65. doi: 10.1016/j.ahj.2011.09.012. Epub 2011 Nov 8.

  PMID: 22137067 BACKGROUND

• Rosengren SM, Young AS, Taylor RL, Welgampola MS. Vestibular function testing in the 21st century: video head impulse test, vestibular evoked myogenic potential, video nystagmography; which tests will provide answers? Curr Opin Neurol. 2022 Feb 1;35(1):64-74. doi: 10.1097/WCO.0000000000001023.

  PMID: 34889807 BACKGROUND

• Scholtz AW, Hahn A, Stefflova B, Medzhidieva D, Ryazantsev SV, Paschinin A, Kunelskaya N, Schumacher K, Weisshaar G. Efficacy and Safety of a Fixed Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg vs Betahistine Dihydrochloride 16 mg in Patients with Peripheral Vestibular Vertigo: A Prospective, Multinational, Multicenter, Double-Blind, Randomized, Non-inferiority Clinical Trial. Clin Drug Investig. 2019 Nov;39(11):1045-1056. doi: 10.1007/s40261-019-00858-6.

  PMID: 31571128 BACKGROUND

• Sokolova L, Hoerr R, Mishchenko T. Treatment of Vertigo: A Randomized, Double-Blind Trial Comparing Efficacy and Safety of Ginkgo biloba Extract EGb 761 and Betahistine. Int J Otolaryngol. 2014;2014:682439. doi: 10.1155/2014/682439. Epub 2014 Jun 25.

  PMID: 25057270 BACKGROUND

• Agrawal Y, Zuniga MG, Davalos-Bichara M, Schubert MC, Walston JD, Hughes J, Carey JP. Decline in semicircular canal and otolith function with age. Otol Neurotol. 2012 Jul;33(5):832-9. doi: 10.1097/MAO.0b013e3182545061.

  PMID: 22699991 BACKGROUND

MeSH Terms

Conditions

Vertigo

Interventions

Arginine; Starch

Condition Hierarchy (Ancestors)

Vestibular Diseases; Labyrinth Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Polysaccharides

Study Officials

• Martha de Nuestra Señora de San Juan Rodríguez, MD

  CUTonalá

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Patients will be assigned by simple randomization using a table of random numbers to the pharmacological intervention groups. The study treatment and treatment assignment codes will be kept in custody by someone outside the research team. In addition, it will be in charge of the delivery, reception and meticulous counting of the capsules to guarantee the blindness and adherence to the treatment by the patients. This study is considered double-blind since both the principal investigator and the patient are unaware of the pharmacological intervention to which the patients will be assigned. Blinding will be possible thanks to the homologation of the drug and the placebo in both groups with capsules identical in shape, size and colour. In the same way, the medicine will be delivered in bottles of the same size, shape and color, identified only with the allocation code. The blind may be broken in the presence of serious adverse events.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Model Details: Randomized, double-blind clinical trial with a placebo control group.

Study Record Dates

• First Submitted: May 12, 2023
• First Posted: July 6, 2023
• Study Start: May 2, 2023
• Primary Completion: November 1, 2023
• Study Completion: December 30, 2023
• Last Updated: February 15, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)