- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04836533
Enhancing Processing Speed and Executive Functioning in Depressed Older Adults With Computerized Cognitive Training
Optimizing Placebo Effects in Depressed Older Adults: Enhancing Processing Speed and Executive Functioning With Computerized Cognitive Training
Study Overview
Status
Conditions
Detailed Description
Major Depressive Disorder (MDD) is a leading cause of disability, morbidity, and mortality across the lifespan and poses a particularly severe public health problem in late life. Late-life depression (LLD) is highly recurrent, can become chronic, and is often difficult to treat. Antidepressant treatment is often ineffective in this population because of the presence of neurocognitive factors including slow processing speed (PS), executive dysfunction (ED), and cerebrovascular disease (CVD) that interfere with treatment. It is crucial, therefore, that we develop interventions that address antidepressant non-response and dramatically improve the quality of life of millions of vulnerable older adults. We recently determined that an important cause of non-response in this population is impaired expectancy effects, which in turn are compromised by slow speed of processing. We propose, therefore, that antidepressant non-response in older adults with PS deficits is caused by expectancy failure and that targeting PS deficits prior to antidepressant treatment will restore the capacity to form expectations thereby improving antidepressant treatment response. An excellent candidate for improving PS is computerized cognitive training (CCT), i.e., exercises that target, train, and strengthen specific cognitive processes with the use of structured drills and repeated practice.
To test our expectancy-processing speed model, 100 depressed adults age 60 and over with PS deficits will be recruited. Participants will be randomized to either CCT or control (Solitaire) for 4 weeks. Both conditions will train 25 minutes per day, 7 days per week. At the conclusion of this four-week period, patients will be randomly assigned to high versus low expectancy treatment conditions. Patients assigned to the low expectancy condition will be told they will receive either placebo or escitalopram when in fact they will receive escitalopram for eight weeks. Patients assigned to the high expectancy condition will be told they will receive escitalopram for eight weeks. Neuropsychological assessment will occur at baseline and weeks 4 and 12 whereas MRI scans will be conducted at baseline and week 4.
Clinical assessments will be conducted biweekly throughout the study. The goals of this study are to 1) To determine whether PS mediates the relationship between CCT and expectancy, and 2) To compare endpoint depression scores as a function of CCT and expectancy conditions.
At the screening evaluation, informed consent for the screening evaluation is obtained. Participants subsequently undergo a psychiatric clinical interview using the Structured Clinical Interview Diagnostic for DSM-V (SCID-V), 24- item Hamilton Rating Scale for Depression (HRSD), Clinical Global Impressions Scale - Severity (CGI-Severity), Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and Antidepressant Treatment History Form (ATHF) to document depression diagnosis, severity, and medical comorbidity. WAIS-IV Digit Symbol Coding will be completed to determine whether the patient meets inclusion criteria for PS (>1 SD on age adjusted norms). If the patient is eligible for study entry, participation in the research protocol will be discussed and informed consent will be obtained. After consent is obtained, patients will receive a comprehensive baseline neuropsychological assessment and MRI (structural, resting state, and DTI). Neuropsychological assessments include MMSE, WAIS-IV Coding, NIH Toolbox Cognition Battery, NIH Supplement Auditory Verbal Learning Test (Rey), Trail Making Test (Part A and B), Stroop Color-Word Test, and The Letter and Animal Naming Test. These measures will capture global cognitive functioning, processing speed, attention, and response inhibition, and verbal fluency. After testing, patients will be randomized to either CCT or active control for 4 weeks (25'/day, 7 days/week). Patients randomized to CCT will complete seven 25-minute sessions per week for 4 weeks using BrainHQ's Double Decision in the experimental condition (a processing speed exercise) and BrainHQ solitaire in the control condition. At the conclusion of this four-week period, patients will complete a second neuropsychological assessment and a second fMRI (to determine change in resting-state BOLD signal in the CCN). Patients will then be randomly assigned to high versus low expectancy treatment conditions. Patients assigned to the low expectancy condition will be told they will receive either placebo escitalopram when in fact they will receive escitalopram for eight weeks. Patient assigned to the high expectancy condition will be told and they will receive escitalopram for eight weeks. Expectancy is measured at baseline and after informing patients of their randomization status. The difference between their pre and post randomization expectancy regarding treatment improvement is the expectancy effect. At the conclusion of the eight-week clinical trial, the difference in antidepressant response observed between the open and placebo-controlled medication treatments is a measure of the expectancy contribution to outcome. Neuropsychological assessment will occur again at the conclusion of the escitalopram trial (week 12). Clinical assessments will be conducted biweekly throughout the study.
The novel experimental therapeutics approach taken in this proposal cuts across several research themes (prevention and translation) and addresses many of the challenges (digital technology and neural circuits) elaborated in NIMH's Strategic Plan for mental health research in the 21st century. Consistent with NIMH goals, it also develops strategies for tailoring existing interventions to optimize outcomes and elucidates the mechanism by which antidepressant treatment in LLD can be restored.
Study Type
Phase
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10032
- New York State Psychiatric Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age greater than or equal to 60 years
- DSM5 Diagnosis of Major Depressive Disorder (MDD), Persistent Depressive Disorder, or Depression Not Otherwise Specified (NOS)
- Hamilton Rating Scale for Depression (HRSD) score ≥ 20
- Decreased processing speed (1 SD below age-adjusted norms on the WAIS-IV Digit Symbol Coding Test)
- Access to a computer with daily internet access
- Willing to and capable of providing informed consent and complying with all study procedures. At the end of the CCT phase (week 4), depression severity will be reassessed. To be eligible for Phase 2 (SSRI trial), participants will be required to have an HRSD score ≥ 14.
Exclusion Criteria:
- Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months
- History of psychosis, psychotic disorder, mania, or bipolar disorder
- Primary neurological disorder, including dementia, stroke, Parkinson's disease, epilepsy, etc.
- Mini Mental Status Examination (MMSE) score less than 24
- HRSD suicide item greater than 2 or Clinical Global Impressions (CGI)-Severity score of 7 at baseline
- History of allergic or adverse reaction to escitalopram, or non-response to adequate trial of escitalopram (at least 4 weeks at dose of 20 mg) during the current episode
- Current or recent (within the past 2 weeks) treatment with psychotherapy, antidepressants, antipsychotics, mood stabilizers
- Contraindication to MRI scanning (such as metal in body) or inability to tolerate the scanning procedures
- History of significant radioactivity exposure (nuclear medicine studies or occupational exposure).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Factorial Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Computerized Cognitive Training
Those assigned to the computerized cognitive training arm prior to antidepressant trial enrollment will receive computerized cognitive training that includes games that scale in difficulty.
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Participants will complete 4 weeks of executive functioning / processing speed training through the BrainHQ platform on their personal computers.
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Active Comparator: Solitaire Training
Those assigned to the solitaire training arm prior to antidepressant trial enrollment will receive computerized solitaire games.
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Participants will complete 4 weeks of Solitaire training through the BrainHQ platform on their personal computers.
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Experimental: Open-label antidepressant treatment
Those assigned to receive open-label antidepressant treatment will begin with 10 mg of escitalopram.
If the participant cannot tolerate or has an adverse reaction to escitalopram, duloxetine will be offered instead.
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Participants will be assigned to open-label or placebo-controlled antidepressant treatment for 8 weeks.
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Placebo Comparator: Placebo-controlled antidepressant treatment
Those assigned to the placebo-controlled group will be told that they have a 50/50 chance of receiving either escitalopram or placebo.
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Participants will be told they have a 50/50 chance of receiving a placebo or antidepressant.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Hamilton Rating Scale for Depression (HRSD) Change
Time Frame: Screen, Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12
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Clinician-rated measure of depressive severity composed of 24 questions used to measure changes in depressive symptoms and monitor safety during the study.
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Screen, Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12
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Treatment Credibility Expectancy Scale (CES) - item 4 Change
Time Frame: Baseline, Week 0
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Self-report scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement.
Item 4 measures how much improvement in depression symptoms is expected.
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Baseline, Week 0
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Processing Speed Change - WAIS-IV Coding
Time Frame: Baseline, Weeks 4, 12
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Processing speed will be assessed using Coding from the Wechsler Adult Intelligence Scale-IV (WAIS-IV), the NIH Toolbox Pattern Comparison Processing Speed Test, and Trail Making Test A. From these 3 tests, a composite score (primary outcome) is derived by extracting a latent factor and factor loadings, creating a purer measure of processing speed than raw scores from an individual test or a sum total score.
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Baseline, Weeks 4, 12
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Processing Speed Change - NIHH Toolbox Pattern Comparison Processing Speed Test
Time Frame: Baseline, Weeks 4, 12
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Processing speed will be assessed using Coding from the Wechsler Adult Intelligence Scale-IV (WAIS-IV), the NIH Toolbox Pattern Comparison Processing Speed Test, and Trail Making Test A. From these 3 tests, a composite score (primary outcome) is derived by extracting a latent factor and factor loadings, creating a purer measure of processing speed than raw scores from an individual test or a sum total score.
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Baseline, Weeks 4, 12
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Processing Speed Change - Trail Making Test A
Time Frame: Baseline, Weeks 4, 12
|
Processing speed will be assessed using Coding from the Wechsler Adult Intelligence Scale-IV (WAIS-IV), the NIH Toolbox Pattern Comparison Processing Speed Test, and Trail Making Test A. From these 3 tests, a composite score (primary outcome) is derived by extracting a latent factor and factor loadings, creating a purer measure of processing speed than raw scores from an individual test or a sum total score.
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Baseline, Weeks 4, 12
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Resting State Functional Connectivity Index Change
Time Frame: Baseline, Week 4
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Measure of resting state fMRI.
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Baseline, Week 4
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Secondary Clinical Global Impressions (CGI) Severity and Improvement
Time Frame: Screen, Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12
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Scales measuring the clinician's view of subjects' global functioning that will provide a clinical assessment of subjects at each visit and help maintain safety by identifying clinical worsening.
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Screen, Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12
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Inventory for Depressive Symptomatology Self-Report (IDS-SR)
Time Frame: Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12
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The IDS-SR is a standard self-report measure of depression severity that will be used to measure changes in depressive symptoms and monitor safety during the study.
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Weeks 0, 1, 2, 3, 4, 6, 8, 10, 12
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Cumulative Illness Rating Scale for Geriatrics (CIRS-G)
Time Frame: Screen
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Provides quantitative ratings of chronic illness burden.
Presence of illness is rated from 0 to 4 in 14 different medical domains.
Scores range from 0-56.
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Screen
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NIH Toolbox Auditory Verbal Learning Test - Rey (RAVLT)
Time Frame: Baseline, Weeks 4, 12
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Measures immediate recall.
Unrelated words presented via audio recording and participant recalls as many as possible
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Baseline, Weeks 4, 12
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Stroop Color-Word Test (Stroop)
Time Frame: Measure of response inhibition sensitive to frontal lobe dysfunction. This test is divided into three conditions: color naming, word reading, and colorword inhibition.
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Baseline, Weeks 4, 12
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Measure of response inhibition sensitive to frontal lobe dysfunction. This test is divided into three conditions: color naming, word reading, and colorword inhibition.
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Letter and Animal Naming Test
Time Frame: Baseline, Weeks 4, 12
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Test measuring the verbal fluency component of executive functioning.
Requires subjects to generate words that begin with a particular letter or belong to a particular semantic category as quickly as possible
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Baseline, Weeks 4, 12
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World Health Organization Disability Assessment Schedule 2.0 (WHODAS2.0)
Time Frame: Screen, Weeks 4, 6, 8, 10, 12
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This 36-item self-report provides a global measure of disability and 7 domain-specific scores based on the conceptual framework of the International Classification of Functioning, Disability, and Health (ICF).
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Screen, Weeks 4, 6, 8, 10, 12
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Trail Making Test A and B
Time Frame: Baseline, Weeks 4, 12
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Paper and pencil test that assesses (A) speeded attention and (B) the switching component of executive function.
This test has two conditions: (A) number sequencing and (B) number-letter sequencing.
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Baseline, Weeks 4, 12
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NIH Toolbox Flanker Inhibitory Control and Attention Test
Time Frame: Baseline, Weeks 4, 12
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Measures attention and executive functioning.
The allocation of one's limited capacities to deal with an abundance of environmental stimulation
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Baseline, Weeks 4, 12
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NIH Toolbox Picture Sequence Memory Test
Time Frame: Baseline, Weeks 4, 12
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Measures episodic memory.
Cognitive processes involved in the acquisition, storage, and retrieval of new information.
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Baseline, Weeks 4, 12
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NIH Toolbox List Sorting Working Memory Test
Time Frame: Baseline, Weeks 4, 12
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Measures working memory.
The ability to store information until the amount of information to be stored exceeds one's capacity to hold that information.
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Baseline, Weeks 4, 12
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NIH Toolbox Picture Vocabulary Test
Time Frame: Baseline, Weeks 4, 12
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Measures receptive vocabulary administered in a computer-adaptive test (CAT) format.
Respondents select the picture that most closely matches the meaning of the word.
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Baseline, Weeks 4, 12
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NIH Toolbox Oral Reading Recognition Test
Time Frame: Baseline, Weeks 4, 12
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Measures reading and decoding skill and crystallized abilities.
Participant is asked to read and pronounce letters and words as accurately as possible.
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Baseline, Weeks 4, 12
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NIH Toolbox Dimensional Card Change Sort Test
Time Frame: Baseline, Weeks 4, 12
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Measures executive function.
The capacity to plan, organize and monitor the executive of behaviors that are strategically directed in a goal-oriented manner.
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Baseline, Weeks 4, 12
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NIH Toolbox Pattern Comparison Processing Speed Test
Time Frame: Baseline, Weeks 4, 12
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Assesses the amount of information that can be processed within a certain unit of time.
Items are simple so as to purely measure processing speed.
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Baseline, Weeks 4, 12
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Diffusion Tensor Imaging (fractional anisotropy and mean diffusivity)
Time Frame: Baseline, Week 4
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Measures of brain white matter integrity.
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Baseline, Week 4
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Structured Clinical Interview Diagnostic for DSM-V (SCIDV)
Time Frame: Screen
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Structured clinical interview to assess current and past psychiatric diagnoses.
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Screen
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Mini-Mental Status Exam (MMSE)
Time Frame: Screen
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A brief, structured 30-item mental status examination that measures concentration or working memory, language and praxis, orientation, memory, and attention span
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Screen
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Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Symbol Coding
Time Frame: Screen, Weeks 4, 12
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Participants are required to copy symbols paired with numbers in a 120 second time limit.
The score is the number correct in the allotted time.
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Screen, Weeks 4, 12
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Collaborators and Investigators
Investigators
- Principal Investigator: Joel R Sneed, PhD, Queens College and NYSPI
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MH126187
- R33MH126187 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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