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A Trial of Magnesium Dependent Tinnitus

A Phase III Trial of Magnesium Dependent Tinnitus

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01273883
Enrollment
38
Registered
2011-01-11
Start date
2011-07-31
Completion date
2013-10-31
Last updated
2015-04-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tinnitus

Keywords

hearing, magnesium

Brief summary

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).

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.

Interventions

DIETARY_SUPPLEMENTMagnesium

Magnesium 532 mg a day

OTHERPlacebo

matching form/dosage

Sponsors

Mayo Clinic
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Tinnitus Distress RatingPre-treatment, Post-treatment, up to four weeksThis is a single-item patient-reported distress rating on a 0-10 scale, with 0=no tinnitus to 10=worst possible tinnitus.

Secondary

MeasureTime frameDescription
Comparison of Average Tinnitus Handicap Inventory (THI) Across All SubjectsPre-treatment, Post-treatment, up to four weeksThe 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.
Comparison of Average Tinnitus Handicap Inventory (THI) Across All MenPre-treatment, Post-treatment, up to four weeksThe 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.
Comparison of Average Tinnitus Handicap Inventory (THI) Across All WomenPre-treatment, Post-treatment, up to four weeksThe 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.

Countries

United States

Participant flow

Participants by arm

ArmCount
Entire Study Population
Includes groups randomized to receive magnesium first and placebo first.
38
Total38

Withdrawals & dropouts

PeriodReasonFG000FG001
First InterventionAdverse Event21
Second InterventionLack of Efficacy10
Second InterventionLost to Follow-up11

Baseline characteristics

CharacteristicEntire Study Population
Age, Continuous61.45 years
STANDARD_DEVIATION 11.58
Region of Enrollment
United States
38 participants
Sex: Female, Male
Female
13 Participants
Sex: Female, Male
Male
25 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
7 / 383 / 38
serious
Total, serious adverse events
0 / 380 / 38

Outcome results

Primary

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.

Time frame: Pre-treatment, Post-treatment, up to four weeks

Population: Not all subjects completed the distress rating scale.

ArmMeasureGroupValue (MEAN)Dispersion
MagnesiumTinnitus Distress RatingPre-treatment5.71 units on a scaleStandard Deviation 1.94
MagnesiumTinnitus Distress RatingPost-treatment5.36 units on a scaleStandard Deviation 2.3
PlaceboTinnitus Distress RatingPre-treatment5.82 units on a scaleStandard Deviation 1.94
PlaceboTinnitus Distress RatingPost-treatment5.46 units on a scaleStandard Deviation 1.99
Secondary

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.

Time frame: Pre-treatment, Post-treatment, up to four weeks

Population: Not all male subjects completed the THI questionnaire.

ArmMeasureGroupValue (MEAN)Dispersion
MagnesiumComparison of Average Tinnitus Handicap Inventory (THI) Across All MenPre-treatment29.1 units on a scaleStandard Deviation 24.7
MagnesiumComparison of Average Tinnitus Handicap Inventory (THI) Across All MenPost-treatment27.8 units on a scaleStandard Deviation 21.5
PlaceboComparison of Average Tinnitus Handicap Inventory (THI) Across All MenPre-treatment27.2 units on a scaleStandard Deviation 22
PlaceboComparison of Average Tinnitus Handicap Inventory (THI) Across All MenPost-treatment25.3 units on a scaleStandard Deviation 19.6
Secondary

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.

Time frame: Pre-treatment, Post-treatment, up to four weeks

Population: Not all subjects completed the THI questionnaire.

ArmMeasureGroupValue (MEAN)Dispersion
MagnesiumComparison of Average Tinnitus Handicap Inventory (THI) Across All SubjectsPre-treatment25.7 units on a scaleStandard Deviation 22.2
MagnesiumComparison of Average Tinnitus Handicap Inventory (THI) Across All SubjectsPost-treatment24.1 units on a scaleStandard Deviation 19.9
PlaceboComparison of Average Tinnitus Handicap Inventory (THI) Across All SubjectsPre-treatment25.7 units on a scaleStandard Deviation 19.4
PlaceboComparison of Average Tinnitus Handicap Inventory (THI) Across All SubjectsPost-treatment23.2 units on a scaleStandard Deviation 17.4
Secondary

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.

Time frame: Pre-treatment, Post-treatment, up to four weeks

Population: Not all the female subjects completed the THI questionnaire.

ArmMeasureGroupValue (MEAN)Dispersion
MagnesiumComparison of Average Tinnitus Handicap Inventory (THI) Across All WomenPost-treatment16.4 units on a scaleStandard Deviation 14.4
MagnesiumComparison of Average Tinnitus Handicap Inventory (THI) Across All WomenPre-treatment18.7 units on a scaleStandard Deviation 14.7
PlaceboComparison of Average Tinnitus Handicap Inventory (THI) Across All WomenPre-treatment22.6 units on a scaleStandard Deviation 12.7
PlaceboComparison of Average Tinnitus Handicap Inventory (THI) Across All WomenPost-treatment18.4 units on a scaleStandard Deviation 10.9

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026