Clinical trial NCT01333098: Antiglucocorticoid Therapy for Cognitive Impairment in Late-life Anxiety Disorders
Official title: Antiglucocorticoid Therapy for Cognitive Impairment in Late-life Anxiety Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Anxiety Disorders
Keywords: anxiety
older adult
memory
cognitive
Saint Louis
treatment
cognitive impariment
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2011-04-11
Enrollment: 15
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Drug Acceptability, as Measured by Number of Participants With Dose-limiting Side Effects
timeFrame: Baseline, Week 2, Week 4
measure: Number of Participants With Self-reported Side Effects
timeFrame: 4 weeks
measure: Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures.
timeFrame: Baseline, Week 4, Week 12
Secondary outcomes:
measure: Anxiety Symptoms
timeFrame: baseline, week 4, week 12
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Eric J Lenze, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.