A Trial of Magnesium Dependent Tinnitus

A Phase III Trial of Magnesium Dependent Tinnitus

The purpose of this study was to examine any potential benefit in lessening the severity of tinnitus (ringing or booming sensation in one or both ears) in subjects supplemented with magnesium (532 mg daily).

Study Overview

• Status: Completed
• Conditions: Tinnitus
• Intervention / Treatment: Dietary supplement: Magnesium; Other: Placebo

Detailed Description

Descriptions of tinnitus date back to the time of ancient Egypt, yet science has failed to unravel the mysterious underlying mechanisms that produce these subjective auditory perceptions of sound. These perceptions may be manifestations of damage resulting from noise exposure, ototoxicity, or other abnormal conditions of the auditory system. However, many individuals have idiopathic tinnitus for which no specific cause can be determined. Although often presenting in conjunction with hearing loss, the magnitude of hearing loss does not necessarily correspond with the severity of tinnitus. In addition, some individuals reporting tinnitus experience concomitant hyperacusis. This relationship suggests these processes may be linked by underlying imbalances at the level of the hair cell. The possible influence of magnesium (Mg) and its antagonist, calcium, has been discussed in the literature as a contributing factor in the mitigation of noise-induced hearing loss, ototoxicity, and the hyperexcitability of the auditory system. Permanent and temporary changes in auditory function have been linked to nutritional deficiencies of magnesium. Mg deficiency has resulted in increased susceptibility to noise-induced hearing loss, ototoxicity, and hyperexcitability of the auditory system.

The recommended daily allowance (RDA) for Mg in adults is 4.5 mg/kg; however, all age groups of Americans fall short of the RDA for Mg by 100 mg daily. This lack of appropriate magnesium intake may have negative consequences. For example, the putative Mg mechanism within the auditory system involves a metabolic cellular cascade of events. Specifically, Mg deficiency leads to increased permeability of the calcium channel in the hair cells with a consequent over-influx of calcium, an increased release of glutamate via exocytosis, and overstimulation of N-methyl-D-aspartate receptors on the auditory nerve fibers. Recent studies of both noise-induced hearing loss and idiopathic sensorineural hearing loss have suggested that Mg supplementation may lessen the severity of tinnitus in patients. Mg improved hearing recovery and lessened tinnitus in patients with idiopathic sudden hearing loss. More recently, a well-controlled study that Mg was a relatively safe and convenient adjunct to corticosteroid treatment for enhancing the improvements of hearing in acute-onset sensorineural hearing loss at a dose of 4 g. The protective effect of Mg in noise-induced hearing loss has been previously reported.

Despite these encouraging findings, no controlled study has examined the effect of Mg supplementation for subjects with moderate to severe tinnitus.

In this study subjects made 4 visits to the clinic over about 2 months. At the first visit, subjects had a hearing test. Prior to beginning each round of supplements, subjects were asked to rate the severity of their tinnitus on a 1-10 scale, and to complete the Tinnitus Handicap Inventory (THI) questionnaire. Subjects were then randomized to 1 of 2 groups. One group began with 532 mg of Mg for 25 days, the other group began with a placebo supplement for 25 days.

At visit 2, the subjects had a hearing test, rated their tinnitus, and completed the THI questionnaire as well as the Treatment Period Survey. Subjects did not take any supplement for 2 weeks, then returned for visit 3.

At Visit 3, the subjects had a hearing test, rated their tinnitus, and completed the THI questionnaire they then took the opposite supplement (placebo or Mg) for 25 days.

At Visit 4, the subjects had a hearing test, rated their tinnitus, and completed the THI questionnaire as well as the Treatment Period Survey.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Normal Kidney function (last checked within 6 months). Serum creatinine levels 1.5 mg/dL or below for females, 2.0 mg/dL for males.
• An audiogram within the past 6 months
• Mayo Clinic patients who live in Phoenix area

Exclusion criteria:

• Any participant with decreased kidney function within past 6 months, over 1.5 mg/dL for females and over 2.0 mg/dL for males.
• Current treatment with Lithium
• Tinnitus rating with 0, 1, or 2 on the 0-10 Tinnitus scale

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Magnesium first, then placebo; Magnesium 532 mg daily for 25 days followed by 2 weeks of washout followed by 25 days of placebo.	Dietary supplement: Magnesium; Magnesium 532 mg a day; Other: Placebo; matching form/dosage
Placebo Comparator: Placebo first, then magnesium; Placebo daily for 25 days followed by 2 weeks of washout followed by magnesium 532 mg daily for 25 days.	Dietary supplement: Magnesium; Magnesium 532 mg a day; Other: Placebo; matching form/dosage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tinnitus Distress Rating	This is a single-item patient-reported distress rating on a 0-10 scale, with 0=no tinnitus to 10=worst possible tinnitus.	Pre-treatment, Post-treatment, up to four weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Average Tinnitus Handicap Inventory (THI) Across All Subjects	The Tinnitus Handicap Inventory measures the extent that tinnitus interferes with daily activities and sleep.The questionnaire consists of 25 questions, the score can range from 0 (slight problem) to 100 (catastrophic). The score can be converted to a categorical variable as follows: 0-16=Slight; 18-36=Mild; 38-56=Moderate; 58-76=Severe; 78-100=Catastrophic.	Pre-treatment, Post-treatment, up to four weeks
Comparison of Average Tinnitus Handicap Inventory (THI) Across All Men	The Tinnitus Handicap Inventory measures the extent that tinnitus interferes with daily activities and sleep.The questionnaire consists of 25 questions, the score can range from 0 (slight problem) to 100 (catastrophic). The score can be converted to a categorical variable as follows: 0-16=Slight; 18-36=Mild; 38-56=Moderate; 58-76=Severe; 78-100=Catastrophic.	Pre-treatment, Post-treatment, up to four weeks
Comparison of Average Tinnitus Handicap Inventory (THI) Across All Women	The Tinnitus Handicap Inventory measures the extent that tinnitus interferes with daily activities and sleep.The questionnaire consists of 25 questions, the score can range from 0 (slight problem) to 100 (catastrophic). The score can be converted to a categorical variable as follows: 0-16=Slight; 18-36=Mild; 38-56=Moderate; 58-76=Severe; 78-100=Catastrophic.	Pre-treatment, Post-treatment, up to four weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Michael Cevette, PhD, Mayo Clinic

Publications and helpful links

General Publications

• Cevette MJ, Barrs DM, Patel A, Conroy KP, Sydlowski S, Noble BN, Nelson GA, Stepanek J. Phase 2 study examining magnesium-dependent tinnitus. Int Tinnitus J. 2011;16(2):168-73.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: January 7, 2011
• First Submitted That Met QC Criteria: January 10, 2011
• First Posted (Estimate): January 11, 2011

Study Record Updates

• Last Update Posted (Estimate): April 30, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: magnesium; hearing
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Tinnitus
• Other Study ID Numbers: 09-008292

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No