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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| mifepristone | Experimental | 1 week mifepristone or placebo (followed by 3 weeks open label mifepristone) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mifepristone | Drug | 300mg per day, by mouth, for 21-28 days |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eric J Lenze, MD | Washington University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24633761 | Result | Lenze EJ, Hershey T, Newcomer JW, Karp JF, Blumberger D, Anger J, Dore P, Dixon D. Antiglucocorticoid therapy for older adults with anxiety and co-occurring cognitive dysfunction: results from a pilot study with mifepristone. Int J Geriatr Psychiatry. 2014 Sep;29(9):962-9. doi: 10.1002/gps.4085. Epub 2014 Mar 14. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Mifepristone | 1 week mifepristone or placebo, followed by 3 weeks open label mifepristone Mifepristone: 300mg per day, by mouth, for 21-28 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Mifepristone | 1 week mifepristone or placebo followed by 3 weeks open label mifepristone Mifepristone: 300mg per day, by mouth, for 21-28 days |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Drug Acceptability, as Measured by Number of Participants With Dose-limiting Side Effects | number of participants with dose-limiting side effects | Posted | Count of Participants | Participants | Baseline, Week 2, Week 4 |
|
|
Adverse event data was collected during the course of each participant's 12 week participation in the study which took place during a 4 month period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Mifepristone | 1 week mifepristone or placebo (followed by 3 weeks open label mifepristone) Mifepristone: 300mg per day, by mouth, for 21-28 days |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eric Lenze, MD | Washington University School of Medicine | 314-362-5154 | lenzee@wustl.edu |
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| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D015735 | Mifepristone |
| ID | Term |
|---|---|
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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In the first week, participants were randomly assigned to mifepristone 300mg daily or placebo. In the subsequent 3 weeks, all participants received mifepristone 300mg.
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| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
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| Primary | Number of Participants With Self-reported Side Effects | Posted | Number | participants with reported side effects | 4 weeks |
|
|
|
| Primary | 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. | Posted | Mean | Standard Error | z-score | Baseline, Week 4, Week 12 |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Error | Scores on a scale | baseline, week 4, week 12 |
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| 0 |
| 15 |
| 0 |
| 15 |
| 5 |
| 15 |
| Hypokalemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Reduced T4 | Endocrine disorders | Systematic Assessment |
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| Worsening of pre-existing orthostatic hypotension | Cardiac disorders | Systematic Assessment |
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| D011083 |
| Polycyclic Compounds |
| Week 12 |
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| Week 12 |
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