Antiglucocorticoid Therapy for Cognitive Impairment in Late-life Anxiety Disorders

NCT01333098 | Completed Phase 1 Results

• 1 other identifier: 201011836
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Anxiety Disorders

Keywords

anxiety; older adult; memory; cognitive; Saint Louis; treatment; cognitive impariment

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Anxiety Symptoms

  baseline, week 4, week 12

Study Arms (1)

mifepristone

EXPERIMENTAL

1 week mifepristone or placebo (followed by 3 weeks open label mifepristone)

Drug: Mifepristone

Interventions

Mifepristone DRUG

300mg per day, by mouth, for 21-28 days

Also known as: Mifeprex, RU-486

mifepristone

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 24633761 RESULT

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Eric Lenze, MD
• Organization: Washington University School of Medicine

lenzee@wustl.edu

314-362-5154

Study Officials

• Eric J Lenze, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In the first week, participants were randomly assigned to mifepristone 300mg daily or placebo. In the subsequent 3 weeks, all participants received mifepristone 300mg.

Study Record Dates

• First Submitted: March 24, 2011
• First Posted: April 11, 2011
• Study Start: September 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: August 18, 2020
• Results First Posted: March 18, 2019

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)