Anxiety Disorders
Conditions
Keywords
anxiety, older adult, memory, cognitive, Saint Louis, treatment, cognitive impariment
Brief summary
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
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.
Interventions
DRUGMifepristone
300mg per day, by mouth, for 21-28 days
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug Acceptability, as Measured by Number of Participants With Dose-limiting Side Effects | Baseline, Week 2, Week 4 | number of participants with dose-limiting side effects |
| 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. | Baseline, Week 4, Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anxiety Symptoms | baseline, week 4, week 12 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mifepristone 1 week mifepristone or placebo followed by 3 weeks open label mifepristone
Mifepristone: 300mg per day, by mouth, for 21-28 days | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Mifepristone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Age, Continuous | 73.1 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment United States | 15 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 5 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
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.
Time frame: Baseline, Week 4, Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mifepristone | Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures. | Baseline | 0.93 z-score | Standard Error 1.58 |
| Mifepristone | Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures. | Week 4 | 1.85 z-score | Standard Error 1.97 |
| Mifepristone | Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures. | Week 12 | 3.00 z-score | Standard Error 2.2 |
| Without High Baseline Corisol | Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures. | Baseline | -0.59 z-score | Standard Error 1.24 |
| Without High Baseline Corisol | Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures. | Week 4 | -0.45 z-score | Standard Error 1.34 |
| Without High Baseline Corisol | Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures. | Week 12 | -0.26 z-score | Standard Error 1.42 |
Primary
Drug Acceptability, as Measured by Number of Participants With Dose-limiting Side Effects
number of participants with dose-limiting side effects
Time frame: Baseline, Week 2, Week 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mifepristone | Drug Acceptability, as Measured by Number of Participants With Dose-limiting Side Effects | 1 Participants |
Primary
Number of Participants With Self-reported Side Effects
Time frame: 4 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mifepristone | Number of Participants With Self-reported Side Effects | dizziness | 5 participants with reported side effects |
| Mifepristone | Number of Participants With Self-reported Side Effects | fatigue | 3 participants with reported side effects |
| Mifepristone | Number of Participants With Self-reported Side Effects | nausea | 2 participants with reported side effects |
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.
Time frame: baseline, week 4, week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mifepristone | Anxiety Symptoms | Week 12 | 23.0 Scores on a scale | Standard Error 6.02 |
| Mifepristone | Anxiety Symptoms | Baseline | 30.80 Scores on a scale | Standard Error 4.27 |
| Mifepristone | Anxiety Symptoms | Week 4 | 22.40 Scores on a scale | Standard Error 6.09 |
| Without High Baseline Corisol | Anxiety Symptoms | Week 12 | 25.29 Scores on a scale | Standard Error 2.39 |
| Without High Baseline Corisol | Anxiety Symptoms | Week 4 | 27.00 Scores on a scale | Standard Error 1.51 |
| Without High Baseline Corisol | Anxiety Symptoms | Baseline | 27.88 Scores on a scale | Standard Error 1.85 |