Effect of Combined Antioxidant Therapy on Oxidative Stress Markers and Inflammatory Cytokines in Patients With Tinnitus

NCT05646693 | Unknown Phase 2 DMC

• 1 other identifier: ACSE202208/IIA
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of our study is to evaluate the effect of combinated antioxidants therapy with Adepsique® (amitriptyline, perphenazine, and diazepam) on patients with tinnitus chronic symptoms, evaluating the levels of inflammatory cytokines and oxidative stress in blood. The researchers intend to include 58 patients, divided into two intervention groups, who will be randomly assigned a pill with antioxidants or placebo, and the patient must eat one pill per day for 3 months. In the study, the clinical characteristics of tinnitus, inflammatory cytokines and oxidative stress markers will be evaluated, before, during and after the intervention with antioxidant therapy. Subsequently, the clinical and sample results will be evaluated to compare the effects between them.

Conditions

Tinnitus, Subjective; Tinnitus, Bilateral; Antioxidant Therapy; Psychiatric Drugs; Oxidative Stress; Inflammatory Cytokines; SSRI

Keywords

Tinnitus

Outcome Measures

Primary Outcomes (10)

• Change from baseline in levels of Superoxide Dismutase (SOD)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The enzyme concentration will be determined with multiplex bead immunoassays technique and reported in microunits per milliliter units (mUI/mL)

  90 days

• Change from baseline in levels of Catalase (CAT)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The enzyme concentration will be determined with multiplex bead immunoassays technique and reported in microunits per milliliter units (mUI/mL)

  90 days

• Change from baseline in levels of Glutathione Peroxidase (GPx)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The enzyme concentration will be determined with multiplex bead immunoassays technique and reported in microunits per milliliter units (mUI/mL)

  90 days

• Change from baseline in levels of Malondialdehyde (MDA)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The enzyme concentration will be determined with multiplex bead immunoassays technique and reported in microunits per milliliter units (mUI/mL)

  90 days

• Change from baseline in levels of Oxidized Low-Density Lipoprotein LDL (oxLDL)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The enzyme concentration will be determined with multiplex bead immunoassays technique and reported in nanograms per milliliter units (ng/mL)

  90 days

• Change from baseline in levels of Tumor Necrosis Factor Alpha (TNF-a)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)

  90 days

• Change from baseline in levels of Interleukin 8 (IL-8)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)

  90 days

• Change from baseline in levels of Interleukin 6 (IL-6)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)

  90 days

• Change from baseline in levels of Gamma Interferon (IFN-γ)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in picogram per milliliter units (pg/mL)

  90 days

• Change from baseline in levels of Nuclear Factor Kappa B (NF-κB)

  Standard blood sampling will be collected through a catheter in an antecubital vein in tubes without EDTA, centrifuged and serum will placed in an eppendorf tube at -80 celsius degrees. The cytokine concentration will be determined with multiplex bead immunoassays technique and reported in nanogram per milliliter units (ng/mL)

  90 days

Secondary Outcomes (5)

• Change from baseline in Tinnitus Loudness (db) Assessment

  90 days

• Change from baseline in Tinnitus Frecuency (Hz) Assessment

  90 days

• Change from baseline in Audiometric Assessment

  90 days

• Change from baseline in Tinnitus Discomfort Assessment

  90 days

• Change from baseline in levels of Otolin-1

  90 days

Study Arms (2)

Drusen Mega® + Sertraline

EXPERIMENTAL

It will consist of 29 patients with Chronic Subjetive Endotic Tinnitus. Patients will eat one capsule of antioxidant therapy (Drusen Mega®) and one capsule of sertraline per day in the night for 3 months.

Dietary Supplement: Drusen Mega®; Drug: Sertraline

Placebo + Sertraline

PLACEBO COMPARATOR

It will consist of 29 patients with Chronic Subjetive Endotic Tinnitus. Patients will eat one capsule of placebo (Magnesium Oxide 100mg) per day in the morning and one capsule of sertraline per day in the night for 3 months.

Drug: Sertraline; Drug: Placebo

Interventions

Drusen Mega® DIETARY_SUPPLEMENT

It consists of a dietary supplement composed of Vitamin C 60.0mg, Vitamin E 30.0mg, Zinc 12.5mg, Copper 1.0mg, Astaxanthin 4.0mg, Zeaxanthin 2.0mg, Lutein 10.0mg and Omega 3 Acids 500.0mg. It is suggested to consume one capsule per day, preferably with food. This supplement is indicated for nutritional deficiencies and in patients with ophthalmological pathologies.

Also known as: Multivitamins

Drusen Mega® + Sertraline

Sertraline DRUG

It consists of a drug capsule composed of Sertraline Hydrochloride 50mg. In adults it is suggested to consume one to four capsule(s) per day, administering (preferably) the highest dose in the evening, before going to bed. This drug is indicated in the treatment of depressive states with anxiety or moderate to severe agitation, which are accompanied by tension, excitement, insomnia, obsessive and hypochondriac traits. It is also indicated in obsessive-compulsive disorder, panic attacks, stress disorder, post-traumatic disorder, social anxiety disorder and used to relieve the symptoms of premenstrual dysphoric disorder.

Also known as: Sertraline Hydrochloride

Drusen Mega® + Sertraline; Placebo + Sertraline

Placebo DRUG

It consists of a placebo capsule composed of Magnesium Oxide 100mg. This component is inert in the dose at which it will be administered.

Also known as: Magnesium Oxide

Placebo + Sertraline

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female with subjective chronic tinnitus (unilateral or bilateral)
• Patients with normal audiometry or identification of hearing loss up to a medium degree (20-70 dB)
• Patients with evidence of endotic tinnitus
• Patients who have or do not have social medical security
• Females of childbearing age with a negative pregnancy test and use of oral contraceptives
• Patients under pharmacological management with a period of stable medication (≥3 months) for chronic degenerative diseases and under good metabolic control (according to ADA 2022 criteria) through primary intervention

You may not qualify if:

• Presence of tinnitus secondary to head trauma, acoustic trauma, or sudden hearing loss
• History or presence of Ménière's disease, otosclerosis, acute or chronic otitis media
• Active gastrointestinal haemorrhagic disease
• History or presence of cancer (any type) or submission to radio and/or chemotherapy
• Autoimmune disease (any)
• History of severe cardiovascular disease (myocardial infarction, stroke, severe peripheral vascular disease)
• Benign prostatic hyperplasia
• Blood dyscrasias and/or bleeding diathesis
• Thyroid disease (any)
• Temporomandibular joint dysfunction
• Neurodegenerative processes
• Hepatic and renal failure
• Closed or open angle glaucoma
• Intake of any medication belonging to the following families (Anticoagulants, Benzodiazepines, ASA diuretics, Aminoglycosides, Chemotherapeutics, Acetylsalicylic Acid, Quinine, MAOIs)
• Intake of antioxidants in the last 6 months

Sponsors & Collaborators

• University of Guadalajara: lead
• Institute of Experimental and Clinical Therapeutics: collaborator
• Hospital Civil de Guadalajara: collaborator

Study Sites (1)

Institute of Experimental and Clinical Therapeutics,

Guadalajara, Jalisco, 44340, Mexico

RECRUITING

Related Publications (10)

• Henry JA, Dennis KC, Schechter MA. General review of tinnitus: prevalence, mechanisms, effects, and management. J Speech Lang Hear Res. 2005 Oct;48(5):1204-35. doi: 10.1044/1092-4388(2005/084).

  PMID: 16411806 BACKGROUND

• Weber C, Arck P, Mazurek B, Klapp BF. Impact of a relaxation training on psychometric and immunologic parameters in tinnitus sufferers. J Psychosom Res. 2002 Jan;52(1):29-33. doi: 10.1016/s0022-3999(01)00281-1.

  PMID: 11801262 BACKGROUND

• Gomaa NA, Jimoh Z, Campbell S, Zenke JK, Szczepek AJ. Biomarkers for Inner Ear Disorders: Scoping Review on the Role of Biomarkers in Hearing and Balance Disorders. Diagnostics (Basel). 2020 Dec 29;11(1):42. doi: 10.3390/diagnostics11010042.

  PMID: 33383894 BACKGROUND

• Solis-Angeles S, Juarez-Perez CA, Jimenez-Ramirez C, Cabello-Lopez A, Aguilar-Madrid G, Del Razo LM. Prestin and otolin-1 proteins in the hearing loss of adults chronically exposed to lead. Toxicol Appl Pharmacol. 2021 Sep 1;426:115651. doi: 10.1016/j.taap.2021.115651. Epub 2021 Jul 15.

  PMID: 34273409 BACKGROUND

• Esmaili AA, Renton J. A review of tinnitus. Aust J Gen Pract. 2018 Apr;47(4):205-208. doi: 10.31128/AJGP-12-17-4420.

  PMID: 29621860 BACKGROUND

• Celik M, Koyuncu I. A Comprehensive Study of Oxidative Stress in Tinnitus Patients. Indian J Otolaryngol Head Neck Surg. 2018 Dec;70(4):521-526. doi: 10.1007/s12070-018-1464-7. Epub 2018 Jul 27.

  PMID: 30464909 BACKGROUND

• Polanski JF, Soares AD, de Mendonca Cruz OL. Antioxidant therapy in the elderly with tinnitus. Braz J Otorhinolaryngol. 2016 May-Jun;82(3):269-74. doi: 10.1016/j.bjorl.2015.04.016. Epub 2015 Oct 17.

  PMID: 26547700 BACKGROUND

• Pawlak-Osinska K, Kazmierczak H, Marzec M, Kupczyk D, Bilski R, Mikolajewska E, Mikolajewski D, Augustynska B. Assessment of the State of the Natural Antioxidant Barrier of a Body in Patients Complaining about the Presence of Tinnitus. Oxid Med Cell Longev. 2018 Oct 28;2018:1439575. doi: 10.1155/2018/1439575. eCollection 2018.

  PMID: 30510615 BACKGROUND

• Petridou AI, Zagora ET, Petridis P, Korres GS, Gazouli M, Xenelis I, Kyrodimos E, Kontothanasi G, Kaliora AC. The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial. Nutrients. 2019 Dec 12;11(12):3037. doi: 10.3390/nu11123037.

  PMID: 31842394 BACKGROUND

• Baguley D, McFerran D, Hall D. Tinnitus. Lancet. 2013 Nov 9;382(9904):1600-7. doi: 10.1016/S0140-6736(13)60142-7. Epub 2013 Jul 2.

  PMID: 23827090 RESULT

MeSH Terms

Conditions

Tinnitus

Interventions

Geritol; Sertraline; Magnesium Oxide

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Magnesium Compounds; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Adolfo D Rodríguez-Carrizalez, MD / PhD

  University of Guadalajara

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adolfo D. Rodríguez-Carrizalez, MD / PhD

CONTACT

+52 33 10585200; leinadkit@hotmail.com

Uriel A. Ibarra-Díaz, MD

CONTACT

+52 33 14654244; uriel.ibarra1323@alumnos.udg.mx

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Professor

Model Details: Clinical Trial Phase II A, controlled with placebo

Study Record Dates

• First Submitted: November 25, 2022
• First Posted: December 12, 2022
• Study Start: December 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: April 7, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)