Attention & Memory Impairments in Menopausal Women

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01324024
• Collaborator: Shire (Industry)
• Enrollment: 35
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether a medication called Vyvanse® (lisdexamfetamine; LDX) has an impact on cognitive functioning, specifically measures of sustained attention, verbal encoding and recall and working memory, in menopausal aged women. LDX is a medication used to treat attention deficit hyperactivity disorder (ADHD). The cognitive difficulties that menopausal women report experiencing are typical of adults who are diagnosed with ADHD. The investigators will assess whether or not LDX is effective in alleviating those cognitive disruptions when compared to a placebo.

Condition or Disease	Intervention/Treatment	Phase
Symptomatic Menopause; Cognitive Impairments	Drug: Lisdexamfetamine; Drug: Placebo	Phase 4

Detailed Description

Midlife decline in cognitive function, particularly attention and working memory, is a frequent complaint for which menopausal women seek clinical intervention. Many of the cognitive complaints detected in menopausal women including, short-term memory, organization of tasks, sustaining focus and concentration, and regulating emotions, overlap with symptoms frequently reported by adults with ADHD. These impairments are reported by many women who have no previous history of ADHD, and appear to be linked to reduced estrogen levels occurring in menopause.

This is a double-blind, placebo-controlled, cross-over study testing whether LDX, a stimulant medication, would be effective in alleviating midlife onset impairments of attention and working memory among menopausal women. There will be 3 days in which subjects will undergo a brief cognitive testing assessment; the first testing period will occur at baseline prior to beginning LDX or placebo treatment (PT) in trial A; the second testing period will occur following 4 weeks of double blind LDX or PT; and the final testing period will take place after another 4 weeks of double blind LDX or PT in Trial B. Each cognitive test period will involve 2 separate cognitive testing batteries that will take approximately 120 minutes total to complete.

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Attention & Memory Impairments in Menopausal Women: A Possible Role for Vyvanse?
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lisdexamfetamine, then placebo Participants first received titrated doses of Lisdexamfetamine 20 to 60 mg/d each day for 4 weeks followed by a 2-week washout, then they received Placebo tablets (matching Lisdexamfetamine tablets) each day for 4 weeks.	Drug: Lisdexamfetamine; In a counterbalanced fashion, participants would receive titrated doses of LDX 20 to 60 mg/d for 4 weeks followed by a 2-week washout and then crossed over to the placebo tablets for another 4 weeks. All women will start with LDX 20 mg/d and then be titrated to 40 mg/d after 1 week and 60 mg/d after 2 weeks (as tolerated).; Other Names: Vyvanse® ; Drug: Placebo; In a counterbalanced fashion, participants would receive placebo tablets for 4 weeks followed by a 2 week washout, then will receive titrated doses of LDX 20 to 60 mg/d for 4 weeks.
Experimental: Placebo, then Lisdexamfetamine Participants first received Placebo tablets (matching Lisdexamfetamine tablets) each day for 4 weeks followed by a 2-week washout, then they received titrated doses of Lisdexamfetamine 20 to 60 mg/d each day for 4 weeks.	Drug: Lisdexamfetamine; In a counterbalanced fashion, participants would receive titrated doses of LDX 20 to 60 mg/d for 4 weeks followed by a 2-week washout and then crossed over to the placebo tablets for another 4 weeks. All women will start with LDX 20 mg/d and then be titrated to 40 mg/d after 1 week and 60 mg/d after 2 weeks (as tolerated).; Other Names: Vyvanse® ; Drug: Placebo; In a counterbalanced fashion, participants would receive placebo tablets for 4 weeks followed by a 2 week washout, then will receive titrated doses of LDX 20 to 60 mg/d for 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Brown Attention Deficit Disorder Scale (BADDS) [Baseline, end of first Intervention (4 weeks) and end of second Intervention (4 weeks)]

   The BADDS questionnaire is a clinician administered questionnaire that assesses the frequency and severity of five clusters of symptoms reflective of executive dysfunction reported by individuals with ADHD. Participants are asked to rate the frequency and severity of a symptom on a scale from 0 to 3, with 0 meaning that the problem described does not relate to them and 3 indicating that the problem is very true for them and occurs almost daily. The range of severity for the total BADDS score is 0 to 120, with scores of 55 and above being consistent with full-syndrome ADHD.

Secondary Outcome Measures

1. Penn Continuous Performance Test [Baseline, end of first Intervention (4 weeks) and end of second Intervention (4 weeks)]

   The Penn Continuous Performance Test is a measure of visual attention and vigilance. In this task, a series of red vertical and horizontal lines flash in a digital numeric frame. The participant must press the spacebar whenever the lines form complete numbers or complete letters. The minimum to maximum score range for this task is 0-60 correct responses, with 60 being a perfect score. This data presented in the outcome measure table reflects the total number of correct responses.

2. NYU Paragraph Recall Task [Baseline, end of first Intervention (4 weeks) and end of second Intervention (4 weeks)]

   Subjects hear 2 brief narratives, each containing 19-21 informational bits, and are asked to recall as many details as possible immediately after hearing each paragraph (A and B) and again following a 30 minute delay. Subjects receive credit for each informational bit recalled verbatim. Different paragraphs were read at each assessment. The maximum number of correct responses for paragraph A is 19 and the maximum number of correct responses for paragraph B is 21.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 60 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Women ages 45 to 60 will be eligible for this study if they:

• Are within 5 years of their last menstrual period;

• Are able to give written informed consent;

• Must have clear urine toxicology screen upon recruitment;

• Are fluent in written and spoken English;

• Must have negative urine pregnancy test if still menstruating.

Exclusion Criteria:

• History of seizures;

• History of cardiac disease including known cardiac defect or conduction abnormality;

• Abnormal electrocardiogram during screening;

• Use of estrogen therapy within previous 6 months;

• Current pregnancy or planning to become pregnant.

• Presence of a contraindication to treatment with stimulant medication; this would include the presence of hypertension, coronary disease, atrial fibrillation, and arrhythmia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Penn Center for Women's Behavioral Wellness	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Shire

Investigators

• Principal Investigator: Cynthia N Epperson, MD, University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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Publications

• Epperson CN, Pittman B, Czarkowski KA, Bradley J, Quinlan DM, Brown TE. Impact of atomoxetine on subjective attention and memory difficulties in perimenopausal and postmenopausal women. Menopause. 2011 May;18(5):542-8. doi: 10.1097/gme.0b013e3181fcafd6.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT01324024
• Other Study ID Numbers: 812470
• First Posted: Mar 28, 2011
• Last Update Posted: Jun 28, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by University of Pennsylvania: Menopause; Aging; Memory; Women
• Additional relevant MeSH terms: Lisdexamfetamine Dimesylate

Study Results

Participant Flow

Recruitment Details	55 participants were consented for screening over the course of 2 years at an outpatient research site in Philadelphia, PA.
Pre-assignment Detail	Of the 55 who were consented for screening, 20 did not meet inclusion criteria and of the remaining 35, 32 participants completed the study.

Arm/Group Title	Lisdexamfetamine, Then Placebo	Placebo First, Then Lisdexamfetamine
Arm/Group Description	Participants first received titrated doses of Lisdexamfetamine 20 to 60 mg/d each day for 4 weeks (i.e, 20mg/d for 1 week, 40mg/d for 1 week and 60mg/d for 2 weeks) followed by a 2-week washout, then they received Placebo tablets (matching Lisdexamfetamine tablets) each day for 4 weeks.	Participants first received Placebo tablets (matching Lisdexamfetamine tablets) each day for 4 weeks, followed by a 2-week washout, then they received titrated doses of Lisdexamfetamine 20 to 60 mg/d each day for 4 weeks (i.e, 20mg/d for 1 week, 40mg/d for 1 week and 60mg/d for 2 weeks).
Period Title: First Intervention (4 Weeks)
STARTED	18	17
COMPLETED	18	17
NOT COMPLETED	0	0
Period Title: First Intervention (4 Weeks)
STARTED	18	17
COMPLETED	18	17
NOT COMPLETED	0	0
Period Title: First Intervention (4 Weeks)
STARTED	18	17
COMPLETED	16	16
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Participants were randomized to receive either Lisdexampethamine in titrated doses (20mg/d- 60mg/d) or Placebo tablets (matching Lisdexamphetamine).
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	32 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.1 (2.8)
Sex: Female, Male (Count of Participants)
Female	32 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.3%
Not Hispanic or Latino	30 93.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.1%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 21.9%
White	22 68.8%
More than one race	2 6.3%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Brown Attention Deficit Disorder Scale (BADDS)
Description	The BADDS questionnaire is a clinician administered questionnaire that assesses the frequency and severity of five clusters of symptoms reflective of executive dysfunction reported by individuals with ADHD. Participants are asked to rate the frequency and severity of a symptom on a scale from 0 to 3, with 0 meaning that the problem described does not relate to them and 3 indicating that the problem is very true for them and occurs almost daily. The range of severity for the total BADDS score is 0 to 120, with scores of 55 and above being consistent with full-syndrome ADHD.
Time Frame	Baseline, end of first Intervention (4 weeks) and end of second Intervention (4 weeks)

Outcome Measure Data

Analysis Population Description

Of the 55 participants who were consented for screening, 20 were excluded. Of the remaining 35 subjects, 32 completed both active and placebo treatment trials. The numbers in the lisdexamphetamine and placebo arms reflect the fact that 32 subjects completed both arms. 35 total participant data was analyzed for the baseline arm.

Arm/Group Title	Baseline	Lisdexamfetamine	Sugar Pill
Arm/Group Description	Participants who received Lisdexamfetamine 20	Placebo pill, capsules Lisdexamfetamine: The purpose of this study is to assess whether or not lisdexamfetamine is effective in alleviating cognitive disruptions when compared to a placebo.
Measure Participants	35	32	32
Mean (Standard Deviation) [units on a scale]	35.7 (16.8)	21.2 (16.8)	29.8 (17.7)

2. Secondary Outcome

Title	Penn Continuous Performance Test
Description	The Penn Continuous Performance Test is a measure of visual attention and vigilance. In this task, a series of red vertical and horizontal lines flash in a digital numeric frame. The participant must press the spacebar whenever the lines form complete numbers or complete letters. The minimum to maximum score range for this task is 0-60 correct responses, with 60 being a perfect score. This data presented in the outcome measure table reflects the total number of correct responses.
Time Frame	Baseline, end of first Intervention (4 weeks) and end of second Intervention (4 weeks)

Outcome Measure Data

Analysis Population Description

The numbers in the lisdexamphetamine and placebo arms reflect the fact that 32 subjects completed both arms; 16 participants in each arm. 35 total participant data was analyzed for the baseline arm.

Arm/Group Title	Baseline	Lisdexamfetamine	Sugar Pill
Arm/Group Description	Lisdexamfetamine or Vyvanse Lisdexamfetamine: The purpose of this study is to assess whether or not lisdexamfetamine is effective in alleviating cognitive disruptions when compared to a placebo.	Placebo pill, capsules Lisdexamfetamine: The purpose of this study is to assess whether or not lisdexamfetamine is effective in alleviating cognitive disruptions when compared to a placebo.
Measure Participants	35	32	32
Mean (Standard Deviation) [units on a scale]	53.29 (3.78)	56.37 (3.59)	56.21 (3.27)

3. Secondary Outcome

Title	NYU Paragraph Recall Task
Description	Subjects hear 2 brief narratives, each containing 19-21 informational bits, and are asked to recall as many details as possible immediately after hearing each paragraph (A and B) and again following a 30 minute delay. Subjects receive credit for each informational bit recalled verbatim. Different paragraphs were read at each assessment. The maximum number of correct responses for paragraph A is 19 and the maximum number of correct responses for paragraph B is 21.
Time Frame	Baseline, end of first Intervention (4 weeks) and end of second Intervention (4 weeks)

Outcome Measure Data

Analysis Population Description

The numbers in the lisdexamphetamine and placebo arms reflect the fact that 32 subjects completed both arms; 16 participants in each arm. 35 total participant data was analyzed for the baseline arm.

Arm/Group Title	Baseline	Lisdexamfetamine	Placebo
Arm/Group Description	Participants received titrated doses of Lisdexamfetamine 20 to 60 mg/d each day for 4 weeks (i.e, 20mg/d for 1 week, 40mg/d for 1 week and 60mg/d for 2 weeks).	Participants received Placebo tablets (matching Lisdexamfetamine tablets) each day for 4 weeks.
Measure Participants	35	32	32
Immediate paragraph recall A	7.09 (2.56)	7.48 (2.63)	7.00 (2.70)
Immediate paragraph recall B	6.38 (2.12)	7.45 (3.20)	6.75 (2.53)
Delayed paragraph recall A	4.68 (2.65)	5.90 (3.38)	4.94 (3.02)
Delayed paragraph recall B	7.81 (3.58)	9.77 (3.53)	8.47 (2.97)

Adverse Events

Time Frame	From study start to study completion only
Arm/Group Title	Lisdexamfetamine		Sugar Pill
Arm/Group Description	Lisdexamfetamine or Vyvanse Lisdexamfetamine: The purpose of this study is to assess whether or not lisdexamfetamine is effective in alleviating cognitive disruptions when compared to a placebo.		Placebo pill, capsules Lisdexamfetamine: The purpose of this study is to assess whether or not lisdexamfetamine is effective in alleviating cognitive disruptions when compared to a placebo.
All Cause Mortality
	Lisdexamfetamine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/32 (0%)
Serious Adverse Events
	Lisdexamfetamine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Lisdexamfetamine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/32 (18.8%)		1/32 (3.1%)
Cardiac disorders
increased heart rate	1/32 (3.1%)	1	1/32 (3.1%)	1
Eye disorders
eye irritation	1/32 (3.1%)	1	0/32 (0%)	0
Gastrointestinal disorders
diverticulitis	2/32 (6.3%)	2	0/32 (0%)	0
General disorders
mouth sensitivity	2/32 (6.3%)	2	0/32 (0%)	0
dizziness	0/32 (0%)	0	1/32 (3.1%)	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.