Treating Hearing Loss to Improve Mood and Cognition in Older Adults

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT03321006
• Collaborator: National Institute on Aging (NIA) (NIH)
• Enrollment: 25
• Location: 1
• Arms: 2
• Actual Duration (Months): 36.1
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Age-related hearing loss (ARHL) is the third most common health condition affecting older adults after heart disease and arthritis and is the fifth leading cause of years lived with disability worldwide. Many hearing-impaired older adults avoid or withdraw from social contexts in which background noise will make it difficult to communicate, resulting in social isolation and reduced communication with family and friends.Social isolation and loneliness have been linked to numerous adverse physical and mental health outcomes, including dementia, depression, and mortality, and they may also lead to declining physical activity and the development of the syndrome of frailty. In this project it is hypothesized that untreated ARHL represents a distinct route to developing Late-life Depression (LLD) and that individuals with comorbid ARHL/LLD are unlikely to respond to treatments (i.e., antidepressant medication) that do not treat the underlying hearing problem. Initial studies suggest remediation of hearing loss using hearing aids or cochlear implantation may decrease depressive symptoms acutely and over the course of 6 to 12 months follow-up. However, the clinical significance of these findings is obscured by lack of rigorous control groups, failure to objectively document hearing aid compliance, and enrollment of study populations lacking syndromal depression or even a threshold symptom score.

Condition or Disease	Intervention/Treatment	Phase
Hearing Loss; Depression	Device: Phonak Audeo B-R 90 hearing aid device (Active); Drug: Duloxetine or escitalopram; Device: Audeo B-R 90 hearing aid device (Sham)	Phase 4

Detailed Description

This study will conduct the first clinical trial possessing these design features 40 individuals will be recruited who are aged ≥60 years, diagnosed with a clinically significant depressive disorder, and have moderate ARHL with impaired speech discrimination. Comprehensive baseline psychiatric, audiometric, neuropsychological, and functional assessment will be performed. Participants then will be randomized to receive antidepressant medication (AD) treatment plus full amplification hearing aids or antidepressant medication plus low amplification hearing aids over a 12-week prospective trial. Data from this study could suggest a novel therapeutic strategy for LLD and thereby mitigate its public health burden, while also contributing to the increased recognition and treatment of ARHL more generally.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline
• Actual Study Start Date: May 30, 2018
• Actual Primary Completion Date: May 31, 2021
• Actual Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Antidepressant (AD) + full amplification hearing aids Participant will be randomized to active comparator and will receive escitalopram or duloxetine + active hearing aid for 12 weeks.	Device: Phonak Audeo B-R 90 hearing aid device (Active); Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Full amplification hearing aids will have their gain determined by audiometric profile as per standard clinical practice; Drug: Duloxetine or escitalopram; We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.; Other Names: Cymbalta or Lexapro
Sham Comparator: Antidepressant (AD) + Low amplification (sham) hearing aids Participant will be randomized to sham comparator and will receive escitalopram or duloxetine + sham hearing aid for 12 weeks.	Drug: Duloxetine or escitalopram; We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.; Other Names: Cymbalta or Lexapro ; Device: Audeo B-R 90 hearing aid device (Sham); Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Low amplification hearing aids will be programmed to a hearing threshold of 10dB across all frequencies

Outcome Measures

Primary Outcome Measures

1. Hamilton Rating Score for Depression (HRSD) [12 weeks]

   The patient is rated by a clinician among 24 dimensions (24-item HRSD) with a score on a 3 or 5 point scale. Maximum score is a 74. 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.

Secondary Outcome Measures

1. Clinical Global Impression Severity and Improvement (CGI) [12 weeks]

   Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (range 0-7) that requires the clinician to rate the severity of the patient's illness at the time of assessment: range is from 0 (=normal, not at all ill) to 7 (=extremely ill, among the most extremely ill patients worsening)

2. Social Adjustment Scale Self-Report (SAS-SR) Score [12 weeks]

   The SAS-SR contains 54 questions that measure instrumental and expressive role performance over the past 2 weeks. Each question is rated on a 5-point scale. The overall adjustment score is obtained by summing the scores of all the items and dividing by the number of items answered. The SAS-R overall score ranges from 0-270, with higher questions indication more impairment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥ 60 years

2. diagnosed with Diagnostic and Statistical Manual (DSM) 5 MDD or Persistent Depressive Disorder

3. have duration of depression ≥6 months

4. have 24-item Hamilton Rating Scale for Depression (HRSD) score ≥ 16

5. have moderate to severe symmetric, bilateral hearing loss (combined PTA of >50dB at 2 and 3 kHz)

6. demonstrate impaired speech discrimination scores (60- 100% on 25 word list testing) in one or both ears

7. no prior history of hearing aid use within the past 6 months

8. English speaking

9. are willing to and capable of providing informed consent and complying with study procedures.

Exclusion Criteria:

1. diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months

2. history of psychosis, psychotic disorder, mania, or bipolar disorder

3. diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease

4. Mini Mental Status Examination (MMSE) ≤ 24

5. current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, or mood stabilizers

6. current suicidal ideation (HRSD suicide item > 2) with risk of imminent self-harm

7. any physical or intellectual disability adversely affecting ability to complete assessments

8. acute, severe, or unstable medical or neurological illness

9. contraindication to hearing aid placement

10. significant retrocochlear pathology or organic brain lesion (e.g., acoustic neuroma) responsible for hearing loss.

11. having contraindication (e.g. metal) or unable to tolerate the scanning procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute on Aging (NIA)

Investigators

• Principal Investigator: Bret Rutherford, MD, New York State Psychiatric Institute

Study Documents (Full-Text)

• Study Protocol and Informed Consent Form - Nov 6, 2020
• Statistical Analysis Plan - Jun 2, 2021

More Information

Publications

None provided.

• Responsible Party: Bret Rutherford, Associate Professor of Clinical Psychiatry, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT03321006
• Other Study ID Numbers: 7540; R21AG059130
• First Posted: Oct 25, 2017
• Last Update Posted: Oct 4, 2021
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Bret Rutherford, Associate Professor of Clinical Psychiatry, New York State Psychiatric Institute: Aging; Late Life Depression
• Additional relevant MeSH terms: Hearing Loss; Deafness; Depression; Depressive Disorder; Duloxetine Hydrochloride; Citalopram

Study Results

Participant Flow

Arm/Group Title	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids	Antidepressant (AD) + Full Amplification Hearing Aids
Arm/Group Description	Participant will be randomized to sham comparator and will receive escitalopram or duloxetine + sham hearing aid for 12 weeks. Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study. Audeo B-R 90 hearing aid device (Sham): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Low amplification hearing aids will be programmed to a hearing threshold of 10dB across all frequencies	Participant will be randomized to active comparator and will receive escitalopram or duloxetine + active hearing aid for 12 weeks. Phonak Audeo B-R 90 hearing aid device (Active): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Full amplification hearing aids will have their gain determined by audiometric profile as per standard clinical practice Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.
Period Title: Overall Study
STARTED	14	11
COMPLETED	12	11
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Antidepressant (AD) + Full Amplification Hearing Aids	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids	Total
Arm/Group Description	Participant will be randomized to active comparator and will receive escitalopram or duloxetine + active hearing aid for 12 weeks. Phonak Audeo B-R 90 hearing aid device (Active): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Full amplification hearing aids will have their gain determined by audiometric profile as per standard clinical practice Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.	Participant will be randomized to sham comparator and will receive escitalopram or duloxetine + sham hearing aid for 12 weeks. Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study. Audeo B-R 90 hearing aid device (Sham): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Low amplification hearing aids will be programmed to a hearing threshold of 10dB across all frequencies	Total of all reporting groups
Overall Participants	11	14	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	11 100%	14 100%	25 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.9 (9.2)	75 (6.5)	74.1 (7.7)
Sex: Female, Male (Count of Participants)
Female	7 63.6%	10 71.4%	17 68%
Male	4 36.4%	4 28.6%	8 32%
Race/Ethnicity, Customized (Count of Participants)
White	11 100%	11 78.6%	22 88%
Asian	0 0%	1 7.1%	1 4%
Black/ AA	0 0%	2 14.3%	2 8%
Region of Enrollment (participants) [Number]
United States	11 100%	14 100%	25 100%
Hamilton Rating Scale for Depression (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.9 (4.1)	18.9 (5.4)	19.4 (4.8)
Social Adjustment Scale- Self Report (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	2.5 (0.3)	2.2 (0.4)	2.3 (0.4)

Outcome Measures

1. Primary Outcome

Title	Hamilton Rating Score for Depression (HRSD)
Description	The patient is rated by a clinician among 24 dimensions (24-item HRSD) with a score on a 3 or 5 point scale. Maximum score is a 74. 0-7 are considered as being normal, 8-16 suggest mild depression, 17-23 moderate depression and scores over 24 are indicative of severe depression.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids	Antidepressant (AD) + Full Amplification Hearing Aids
Arm/Group Description	Participant will be randomized to sham comparator and will receive escitalopram or duloxetine + sham hearing aid for 12 weeks. Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study. Audeo B-R 90 hearing aid device (Sham): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Low amplification hearing aids will be programmed to a hearing threshold of 10dB across all frequencies	Participant will be randomized to active comparator and will receive escitalopram or duloxetine + active hearing aid for 12 weeks. Phonak Audeo B-R 90 hearing aid device (Active): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Full amplification hearing aids will have their gain determined by audiometric profile as per standard clinical practice Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.
Measure Participants	12	11
Mean (Standard Error) [score on a scale]	12.04 (1.72)	13.86 (1.67)

2. Secondary Outcome

Title	Clinical Global Impression Severity and Improvement (CGI)
Description	Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale (range 0-7) that requires the clinician to rate the severity of the patient's illness at the time of assessment: range is from 0 (=normal, not at all ill) to 7 (=extremely ill, among the most extremely ill patients worsening)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids	Antidepressant (AD) + Full Amplification Hearing Aids
Arm/Group Description	Participant will be randomized to sham comparator and will receive escitalopram or duloxetine + sham hearing aid for 12 weeks. Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study. Audeo B-R 90 hearing aid device (Sham): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Low amplification hearing aids will be programmed to a hearing threshold of 10dB across all frequencies	Participant will be randomized to active comparator and will receive escitalopram or duloxetine + active hearing aid for 12 weeks. Phonak Audeo B-R 90 hearing aid device (Active): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Full amplification hearing aids will have their gain determined by audiometric profile as per standard clinical practice Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.
Measure Participants	11	11
Mean (Standard Error) [score on a scale]	3.17 (0.33)	3.20 (0.33)

3. Secondary Outcome

Title	Social Adjustment Scale Self-Report (SAS-SR) Score
Description	The SAS-SR contains 54 questions that measure instrumental and expressive role performance over the past 2 weeks. Each question is rated on a 5-point scale. The overall adjustment score is obtained by summing the scores of all the items and dividing by the number of items answered. The SAS-R overall score ranges from 0-270, with higher questions indication more impairment.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids	Antidepressant (AD) + Full Amplification Hearing Aids
Arm/Group Description	Participant will be randomized to sham comparator and will receive escitalopram or duloxetine + sham hearing aid for 12 weeks. Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study. Audeo B-R 90 hearing aid device (Sham): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Low amplification hearing aids will be programmed to a hearing threshold of 10dB across all frequencies	Participant will be randomized to active comparator and will receive escitalopram or duloxetine + active hearing aid for 12 weeks. Phonak Audeo B-R 90 hearing aid device (Active): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Full amplification hearing aids will have their gain determined by audiometric profile as per standard clinical practice Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.
Measure Participants	11	11
Mean (Standard Error) [score on a scale]	1.96 (0.12)	2.10 (0.13)

Adverse Events

Time Frame	Adverse Events, Serious Adverse Events, and All-Cause Mortality were assesed over a period of 12 weeks.
Adverse Event Reporting Description	Our definition of an an adverse event and/or serious adverse event and/or all-cause mortality did not differ from the definition of adverse event and/or serious adverse event or all-cause mortality from the clinicaltrials.gov definitions. Adverse Events, Serious Adverse Events and All-Cause Mortality was assesed over a period of 12 weeks.
Arm/Group Title	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids		Antidepressant (AD) + Full Amplification Hearing Aids
Arm/Group Description	Participant will be randomized to sham comparator and will receive escitalopram or duloxetine + sham hearing aid for 12 weeks. Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study. Audeo B-R 90 hearing aid device (Sham): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Low amplification hearing aids will be programmed to a hearing threshold of 10dB across all frequencies		Participant will be randomized to active comparator and will receive escitalopram or duloxetine + active hearing aid for 12 weeks. Phonak Audeo B-R 90 hearing aid device (Active): Hearing aids will be the latest Audeo B-R 90 devices manufactured by Phonak. Full amplification hearing aids will have their gain determined by audiometric profile as per standard clinical practice Duloxetine or escitalopram: We opted to allow two potential medication choices so that study participation could be offered to individuals who had previously taken one medication and either not responded or not tolerated it. After 4 weeks if subjects do not meet remission criteria (HRSD≤10), the dose of study medication will be increased to escitalopram 20mg or duloxetine 60mg for the remaining 8 weeks of the study.
All Cause Mortality
	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids		Antidepressant (AD) + Full Amplification Hearing Aids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		0/11 (0%)
Serious Adverse Events
	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids		Antidepressant (AD) + Full Amplification Hearing Aids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)		1/11 (9.1%)
Cardiac disorders
Serious Adverse Event	0/14 (0%)	0	1/11 (9.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
All Cause Mortality	1/14 (7.1%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Antidepressant (AD) + Low Amplification (Sham) Hearing Aids		Antidepressant (AD) + Full Amplification Hearing Aids
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

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.