Antiglucocorticoid Therapy for Cognitive Impairment in Late-life Anxiety Disorders

Study Overview
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Brief Summary
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This study seeks to develop and test a novel, mechanistic treatment for mitigating cognitive impairment in older adults with anxiety disorders. Anxiety disorders are common, severe, and disabling in older adults. One particularly impairing aspect of late-life anxiety disorders is cognitive impairment: impairments in memory and executive function cause disability, impede treatment response to psychotherapy, may lead to dementia, and are not corrected by standard anti-anxiety treatments. This pilot study will test the glucocorticoid antagonist, mifepristone, for cognitive impairment in late-life anxiety disorders. Mifepristone blocks the effects of elevated cortisol levels on glucocorticoid receptors in the brain; it has been studied preliminarily in various neuropsychiatric disorders, such as psychotic depression and bipolar disorder, with well-documented safety and tolerability.

Detailed Description
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Currently, no treatment exists to address cognitive impairment in late-life anxiety disorders. In this study, fifteen patients aged 60+ with an anxiety disorder (current or in partial remission) and subjective and/or objective evidence of cognitive impairment will receive treatment with mifepristone. At the baseline visit participants will be randomized to receive either mifepristone 300mg or a placebo daily for 7 days. Participants will be reassessed after 7 days (week 1 visit) of receiving study medication (mifepristone or placebo). At that time all participants will be provided mifepristone 300mg daily for the remaining 3 weeks of study treatment. The primary outcome measure will be neurocognition, as assessed by a battery of neuropsychological measures focusing on immediate and delayed memory and executive function (administered at baseline, week 1, week 4, and week 12). Saliva samples for cortisol measurement will be collected immediately following the baseline visit and week 4 visit. Secondary outcomes will be self-reported anxiety and depressive symptoms.

Official Title
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Antiglucocorticoid Therapy for Cognitive Impairment in Late-life Anxiety Disorders

Conditions
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Anxiety Disorders

Intervention / Treatment
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* Drug: Mifepristone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65 and older Non-demented by clinical evaluation Current or partially remitted generalized anxiety disorder or panic disorder Currently taking antidepressant treatment with stable dose for at least 8 weeks Memory impairment Exclusion Criteria: Mild to severe dementia Diabetes Current alcohol or substance abuse Current or lifetime psychotic symptoms, bipolar disorder, or eating disorder Untreated endocrinologic disease Lifetime Cushing's or Addison's disease Current cancer History of metastatic cancer Current use of systemic corticosteroids

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: In the first week, participants were randomly assigned to mifepristone 300mg daily or placebo. In the subsequent 3 weeks, all participants received mifepristone 300mg.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mifepristone<br>1 week mifepristone or placebo (followed by 3 weeks open label mifepristone) | Drug: Mifepristone<br>* 300mg per day, by mouth, for 21-28 days<br>* Other names: RU-486;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug Acceptability, as Measured by Number of Participants With Dose-limiting Side Effects | number of participants with dose-limiting side effects | Baseline, Week 2, Week 4 | 
| Number of Participants With Self-reported Side Effects |  | 4 weeks | 
| Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures. | Memory composite z-score: The two memory measures were a 16-word list recall similar to the Rey auditory verbal learning test, which has been used by the Washington University Alzheimer's Disease Research Center; and two paragraphs from a set of paragraph recall tests validated as sensitive to effects of stress-level glucocorticoids. For each memory variable, a z score was computed for each participant, where z score = (participant score mean)/standard deviation. Then a single composite memory variable was created by summing up these z scores. Summed Z-scores range from -6 to 6, with scores above 0 being higher than the mean. | Baseline, Week 4, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety Symptoms | Self-report assessment of worry using Penn State Worry Questionnaire- Abbreviated, an 8-item measure (range 8-40 with high scores indicating higher levels of anxiety and worry symptoms.The average score for older adults with generalized anxiety disorder is 22, while the mean score for healthy older adults is 15. | baseline, week 4, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anxiety, older adult, memory, cognitive, Saint Louis, treatment, cognitive impariment