Mifepristone: Antiglucocorticoid Therapy for Cognitive Impairment in Late-life Anxiety Disorders

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01333098
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 7
• Patients Per Site Per Month: 2.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anxiety Disorders	Drug: Mifepristone	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• 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.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)
• Primary Purpose: Treatment
• Official Title: Antiglucocorticoid Therapy for Cognitive Impairment in Late-life Anxiety Disorders
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mifepristone 1 week mifepristone or placebo (followed by 3 weeks open label mifepristone)	Drug: Mifepristone; 300mg per day, by mouth, for 21-28 days; Other Names: Mifeprex RU-486

Outcome Measures

Primary Outcome Measures

1. 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

2. Number of Participants With Self-reported Side Effects [4 weeks]

3. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Eric J Lenze, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• 2012

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01333098
• Other Study ID Numbers: 201011836
• First Posted: Apr 11, 2011
• Last Update Posted: Aug 18, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Washington University School of Medicine: anxiety; older adult; memory; cognitive; Saint Louis; treatment; cognitive impariment
• Additional relevant MeSH terms: Anxiety Disorders; Cognitive Dysfunction; Mifepristone

Study Results

Participant Flow

Arm/Group Title	Mifepristone
Arm/Group Description	1 week mifepristone or placebo, followed by 3 weeks open label mifepristone Mifepristone: 300mg per day, by mouth, for 21-28 days
Period Title: Overall Study
STARTED	15
COMPLETED	12
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Mifepristone
Arm/Group Description	1 week mifepristone or placebo followed by 3 weeks open label mifepristone Mifepristone: 300mg per day, by mouth, for 21-28 days
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 20%
>=65 years	12 80%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.1 (9.1)
Sex: Female, Male (Count of Participants)
Female	11 73.3%
Male	4 26.7%
Region of Enrollment (Count of Participants)
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Drug Acceptability, as Measured by Number of Participants With Dose-limiting Side Effects
Description	number of participants with dose-limiting side effects
Time Frame	Baseline, Week 2, Week 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	1 week mifepristone or placebo, followed by 3 weeks open label mifepristone Mifepristone: 300mg per day, by mouth, for 21-28 days
Measure Participants	15
Count of Participants [Participants]	1 6.7%

2. Primary Outcome

Title	Number of Participants With Self-reported Side Effects
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mifepristone
Arm/Group Description	1 week mifepristone or placebo, followed by 3 weeks open label mifepristone Mifepristone: 300mg per day, by mouth, for 21-28 days
Measure Participants	15
dizziness	5 33.3%
fatigue	3 20%
nausea	2 13.3%

3. Primary Outcome

Title	Cognitive Changes Over Time, as Measured by Between Group and Within-subjects Comparison of Neuropsychological Measures.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Baseline Cortisol	Without High Baseline Corisol
Arm/Group Description	baseline peak cortisol >6 ng/ml	baseline peak cortisol <6 ng/ml
Measure Participants	5	8
Baseline	0.93 (1.58)	-0.59 (1.24)
Week 4	1.85 (1.97)	-0.45 (1.34)
Week 12	3.00 (2.20)	-0.26 (1.42)

4. Secondary Outcome

Title	Anxiety Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	High Baseline Cortisol	Without High Baseline Corisol
Arm/Group Description	baseline peak cortisol >6 ng/ml	baseline peak cortisol <6 ng/ml
Measure Participants	5	8
Baseline	30.80 (4.27)	27.88 (1.85)
Week 4	22.40 (6.09)	27.00 (1.51)
Week 12	23.0 (6.02)	25.29 (2.39)

Adverse Events

Time Frame	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.
Arm/Group Title	Mifepristone
Arm/Group Description	1 week mifepristone or placebo (followed by 3 weeks open label mifepristone) Mifepristone: 300mg per day, by mouth, for 21-28 days
All Cause Mortality
	Mifepristone
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Mifepristone
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Mifepristone
	Affected / at Risk (%)	# Events
Total	5/15 (33.3%)
Blood and lymphatic system disorders
Neutropenia	1/15 (6.7%)	1
Hypokalemia	2/15 (13.3%)	2
Cardiac disorders
Worsening of pre-existing orthostatic hypotension	1/15 (6.7%)	1
Endocrine disorders
Reduced T4	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.