Zinc to Treat Tinnitus in the Elderly

• Sponsor: University of Iowa (Other)
• Overall Status: Completed
• CT.gov ID: NCT00683644
• Collaborator: Tinnitus Research Initiative (Other)
• Enrollment: 116
• Location: 1
• Arms: 2
• Duration (Months): 47
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

There is widespread belief and some evidence to indicate that zinc can successfully treat tinnitus. Zinc deficiency is more likely to occur in the elderly . The primary objective of this study is to establish the effectiveness of zinc for the treatment of tinnitus in individuals 60 years of age and older. Subjects will be randomly assigned to either receive zinc daily or a placebo. After 4 months and a 1-month wash-out, the subjects will be crossed over to the other group.

Condition or Disease	Intervention/Treatment	Phase
Tinnitus	Drug: Zinc; Drug: Placebo oral capsule	Phase 2

Detailed Description

There is widespread belief and some evidence to indicate that zinc can successfully treat tinnitus. Zinc deficiency is more likely to occur in the elderly . The primary objective of this study is to establish the effectiveness of zinc for the treatment of tinnitus in individuals 60 years of age and older. Subjects will be randomly assigned to either receive zinc daily or a placebo. After 4 months and a 1-month wash-out, the subjects will be crossed over to the other group. 116 patients were tested. Tinnitus loudness and the Tinnitus Handicap Questionnaire are the outcome measures.

Study Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: placebo pill
• Primary Purpose: Treatment
• Official Title: Zinc to Treat Tinnitus in the Elderly: A Randomized Placebo Controlled Crossover Trial.
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 - zinc placebo Zinc sulfate (50 mg elemental zinc) taken once daily for 4 months. Washout 1 month. Placebo oral capsule taken once a day for 4 months.	Drug: Zinc; Zinc taken once daily; Other Names: zinc sulfate ; Drug: Placebo oral capsule; Placebo capsules taken once daily; Other Names: Placebo
Experimental: 2 - placebo zinc Placebo oral capsule taken once a day for 4 months. Washout 1 month. Zinc sulfate (50 mg elemental zinc) taken once daily for 4 months.	Drug: Zinc; Zinc taken once daily; Other Names: zinc sulfate ; Drug: Placebo oral capsule; Placebo capsules taken once daily; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Tinnitus Reaction on the Tinnitus Handicap Questionnaire Scores (0-100) at 4 Months [baseline - 4 months]

   Validated questionnaire of tinnitus reactions. Scale 0 (no tinnitus reaction)- 100 (worst tinnitus reaction). Our primary outcome was the difference scores between Tinnitus Handicap Questionnaire (THQ) on baseline and end of treatment on zinc and placebo treatment. As stated by Newman et al., the test-retest variability was 20%, and difference scores greater than this should be considered a significant reduction. Therefore, changes on the difference scores of 20 or greater were considered as a statistically significant and therefore clinically meaningful improvement for THQ. The minimum score is zero and the maximum is 100. 0 is better and 100 is worse. This applies to all outcome measures.

Secondary Outcome Measures

1. Changes on Baseline Tinnitus Magnitude on Tinnitus Loudness Rating Scores (0-100) at 4 Months Treatment [baseline and 4 months]

   Participants should rate their tinnitus loudness on a scale of 0 (no perception of tinnitus) to 100 (highest degree of tinnitus perception).

2. Changes on Baseline Tinnitus Reactions on Tinnitus Annoyance Rating Scores (0-100) at 4 Months Treatment [baseline and 4 months]

   Tinnitus annoyance rate on a scale of 0 (no annoyance) to 100 (maximum degree of annoyance)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 60 years of age or older

• Tinnitus for 6 months or more

• Normal copper levels

• Be generally healthy

Exclusion Criteria:

• Have a treatable otological disorder

• Involved in litigation

• Have or are suspected of having a serious psychiatric problem

• Involved in other treatments for tinnitus

• Are taking drugs which might interact with zinc and result in tinnitus

• Have copper deficiency

• Have Zinc levels above normal

• Are cognitively impaired.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa	Iowa City	Iowa	United States	52242

Sponsors and Collaborators

• University of Iowa
• Tinnitus Research Initiative

Investigators

• Principal Investigator: Richard S. Tyler, Ph.D., University of Iowa

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Richard Tyler, Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT00683644
• Other Study ID Numbers: 200603807
• First Posted: May 23, 2008
• Last Update Posted: Dec 13, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Richard Tyler, Professor, University of Iowa: tinnitus, zinc
• Additional relevant MeSH terms: Tinnitus; Zinc; Zinc Sulfate

Study Results

Participant Flow

Recruitment Details	recruited from audiology clinic in otolaryngology department

Arm/Group Title	Group 1 Zinc First	Group 2 Placebo First
Arm/Group Description	Zinc sulfate (50 mg elemental zinc) taken once daily for 4 months ZINC 4 MONTHS WASHOUT 1 MONTH PLACEBO 4 MONTHS	Placebo capsules taken once a day for 4 months PLACEBO 4 MONTHS WASHOUT 1 MONTH ZINC 4 MONTHS
Period Title: Overall Study
STARTED	58	58
COMPLETED	45	44
NOT COMPLETED	13	14

Baseline Characteristics

Arm/Group Title	Group 1 Zinc First	Group 2 Placebo First	Total
Arm/Group Description	Zinc sulfate 220 mg capsules, (corresponding to 50 mg of elemental zinc) administered once a day for 4 months. Washout period of 30 days. Placebo capsules administered once a day for 4 months.	Placebo capsules administered once a day for 4 months. Washout period of 30 days. Zinc sulfate 220 mg capsules, (corresponding to 50 mg of elemental zinc) administered once a day for 4 months.	Total of all reporting groups
Overall Participants	58	58	116
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.5 (5.5)	67.8 (5.8)	67.8 (5.6)
Sex: Female, Male (Count of Participants)
Female	24 41.4%	20 34.5%	44 37.9%
Male	34 58.6%	38 65.5%	72 62.1%
Region of Enrollment (participants) [Number]
United States	58 100%	58 100%	109 94%
Tinnitus Handicap Questionaire (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	28.4 (20.3)	27.4 (19.2)	27.9 (19.8)
Tinnitus Annoyance Rating Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	60 (22.7)	65.8 (23)	63 (23.1)
Tinnitus Loudness Rating Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	66.7 (16.2)	67.5 (15.1)	67.3 (15.6)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Tinnitus Reaction on the Tinnitus Handicap Questionnaire Scores (0-100) at 4 Months
Description	Validated questionnaire of tinnitus reactions. Scale 0 (no tinnitus reaction)- 100 (worst tinnitus reaction). Our primary outcome was the difference scores between Tinnitus Handicap Questionnaire (THQ) on baseline and end of treatment on zinc and placebo treatment. As stated by Newman et al., the test-retest variability was 20%, and difference scores greater than this should be considered a significant reduction. Therefore, changes on the difference scores of 20 or greater were considered as a statistically significant and therefore clinically meaningful improvement for THQ. The minimum score is zero and the maximum is 100. 0 is better and 100 is worse. This applies to all outcome measures.
Time Frame	baseline - 4 months

Outcome Measure Data

Analysis Population Description

For data analysis purposes subjects were recombined in 2 groups (Zinc and Placebo). Group ZINC: subjects who completed 4 months with Zinc 50 mg daily either from baseline to month 4, or after washout (from month 5 to 9). Group PLACEBO: subjects who completed 4 months with placebo either from baseline to month 4, or after washout (from month 5 to 9)

Arm/Group Title	Zinc	Placebo
Arm/Group Description	Participants that completed 4 months taking Zinc (50 mg) daily, either from baseline to month 4, or after washout period, from month 5 to 9).	Participants that completed 4 months taking placebo capsules daily, either from baseline to month 4 or after a washout period of 1 month (from month 5 to month 9).
Measure Participants	93	94
THQ scores at Baseline	22.03 (22)	24.9 (20.7)
THQ scores at 4 months	23.7 (18.7)	25.4 (21.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zinc, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	The observed power in THQ for zinc is 0.16, and that for placebo is 0.06.
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	Threshold for significance is 0.05
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Changes on Baseline Tinnitus Magnitude on Tinnitus Loudness Rating Scores (0-100) at 4 Months Treatment
Description	Participants should rate their tinnitus loudness on a scale of 0 (no perception of tinnitus) to 100 (highest degree of tinnitus perception).
Time Frame	baseline and 4 months

Outcome Measure Data

Analysis Population Description

Subjects that complete 4 months treatment

Arm/Group Title	Zinc	Placebo
Arm/Group Description	Participants who completed 4 months taking Zinc (50 mg) daily, either from baseline to month 4, or after washout period, from month 5 to 9).	Participants who completed 4 months taking placebo capsules daily, either from baseline to month 4, or after washout period of 1 month (from month 5 to 9).
Measure Participants	93	93
Baseline tinnitus loudness rating scores (SD)	67.7 (18.7)	66 (18.4)
4 months tinnitus loudness rating scores (SD)	68.1 (21.4)	67.6 (20.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zinc
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.89
	Comments	Threshold for significance is 0.05
	Method	paired t test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.36
	Comments	Threshold for significance is 0.05
	Method	paired t test
	Comments

3. Secondary Outcome

Title	Changes on Baseline Tinnitus Reactions on Tinnitus Annoyance Rating Scores (0-100) at 4 Months Treatment
Description	Tinnitus annoyance rate on a scale of 0 (no annoyance) to 100 (maximum degree of annoyance)
Time Frame	baseline and 4 months

Outcome Measure Data

Analysis Population Description

Subjects that complete 4 months treatment

Arm/Group Title	Zinc	Placebo
Arm/Group Description	Zinc sulfate: Zinc sulfate capsules corresponding to 50 mg of elemental zinc, taken once daily. Period of use: 4 months, either on baseline or month 5 (after a washout period: 1 month)	Placebo taken once daily. Period of use: 4 months, either on baseline or month 5 (after a washout period of 1 month)
Measure Participants	93	93
Baseline tinnitus annoyance rating scores	59.67 (25.40)	57.7 (30.85)
4 months tinnitus annoyance rating scores	61 (30.5)	57.9 (26.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zinc
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments	Threshold for significance is 0.05
	Method	paired t test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments	Threshold for significance is 0.05
	Method	paired t test
	Comments

Adverse Events

Time Frame	9 months
Adverse Event Reporting Description	There were 99 participants at risk while receiving Zinc and 101 participants at risk when receiving Placebo.
Arm/Group Title	Zinc		Placebo
Arm/Group Description	54 participants received Zinc first and 45 participants received Zinc after 1 month washout. The total number of participants at risk to Zinc is 99.		55 participants received Placebo first and 46 participants received Placebo after 1 month washout. The total number of participants at risk to Placebo is 101.
All Cause Mortality
	Zinc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/99 (0%)		0/101 (0%)
Serious Adverse Events
	Zinc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/99 (0%)		0/101 (0%)
Other (Not Including Serious) Adverse Events
	Zinc		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/99 (1%)		2/101 (2%)
Gastrointestinal disorders
Indigestion	1/99 (1%)	1	0/101 (0%)	1
Constipation	0/99 (0%)	0	1/101 (1%)	1
Metallic taste	0/99 (0%)	0	1/101 (1%)	1

Limitations/Caveats

For data analysis purposes subjects were divided "per intervention". Zinc: subjects who completed 4 mo with zinc from baseline to month 4, or after washout. Placebo: subjects who completed 4 mo with placebo from baseline to month 4, or after washout.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.