LDX and Functional Magnetic Resonance Imaging (fMRI in Menopausal Women

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT01977625
• Collaborator: Shire (Industry)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 28
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study seeks to assess the effects of lisdexamfetamine (trademark name: Vyvanse; LDX) on executive function and prefrontal cortex activation in menopausal women ages 45-57, who report subjective cognitive difficulties. This protocol will recruit women from Dr. Epperson's ongoing study, Protocol #812470, to examine the impact of LDX on brain activation during performance of cognitive tasks specifically probing prefrontal cortex function.

Condition or Disease	Intervention/Treatment	Phase
Menopause; Brain Activity; Cognition	Drug: Lisdexamfetamine; Other: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Utilizing fMRI to Determine the Effects of Vyvanse® on Memory, Attention, and Brain Activity in Menopausal Women
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lisdexamfetamine Lisdexamfetamine or Vyvanse	Drug: Lisdexamfetamine; The overall objective of this study is to assess the effects of LDX on brain activation patterns during tasks of sustained attention and working memory in menopausal women.; Other Names: Vyvanse®
Placebo Comparator: Sugar Pill Placebo pill, capsules	Other: Placebo; To assess the effects of a placebo pill on brain activation patterns during tasks of sustained attention and working memory in menopausal women.; Other Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Percent Change in Blood Oxygen Level Dependent (BOLD) Signal [10 weeks]

   Blood-oxygen-level dependent contrast imaging, or BOLD-contrast imaging, is a method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time. BOLD signals were compared from baseline, first intervention and second intervention.

Secondary Outcome Measures

1. Change in BADDS Total Score [10 weeks]

   The total BADDS ranged from 0-120 with higher scores meaning greater problems with memory, attention and focus. Difference in BADDS score from Baseline to End of Treatment for each study Arm was calculated.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Have no previous or present history of a DSM-IV psychiatric or substance dependence disorder within the previous year, according to the Structured Clinical Interview for Diagnosis- DSM-IV (SCID)-Non-Patient Version;

2. Are within 5 years of last menstrual period (LMP);

3. Have a follicular stimulating hormone level (FSH) of 20 IU/ml;

4. Are able to give written informed consent;

5. Must have clear urine toxicology screen upon recruitment;

6. Are fluent in written and spoken English;

7. Are right-handed;

8. Negative urine pregnancy test if still menstruating.

Exclusion Criteria:

1. Mini-mental status exam score of less than or equal to 24;

2. Presence of a psychiatric disorder within previous year or a life time history of ADHD or psychotic disorder including bipolar disorder, schizoaffective disorder, and schizophrenia;

3. Lifetime history of drug addiction or abuse, except nicotine;

4. Regular use of other psychotropic medication;

5. Regular use (more than once a week) of alcohol that is less than 3 drinks/day;

6. Presence of a contraindication to treatment with stimulant medication unless the condition is controlled with medication; this would include the presence of uncontrolled hypertension, coronary disease, atrial fibrillation, and arrhythmia;

7. History of seizures;

8. History of cardiac disease including known cardiac defect or conduction abnormality;

9. Abnormal electrocardiogram during screening;

10. Use of estrogen therapy within previous 2 months;

11. Current pregnancy or planning to become pregnant;

12. Metallic implant;

13. Claustrophobia.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania, Penn Center for Womens Behavioral Wellness	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Shire

Investigators

• Principal Investigator: Cynthia Neill Epperson, M.D., University of Pennsylvania

Study Documents (Full-Text)

None provided.

More Information

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: NCT01977625
• Other Study ID Numbers: 814735
• First Posted: Nov 6, 2013
• Last Update Posted: Jul 27, 2018
• Last Verified: Jul 1, 2017

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

Study Results

Participant Flow

Recruitment Details	18 participants were recruited from the parent study NCT01324024 to complete 3 brain imaging scans.
Pre-assignment Detail	Of the 18 participants who were recruited, they all were deemed eligible based on the criteria for the parent study NCT01324024. In addition, they must have been deemed eligible to undergo a functional brain imaging scan. Of these 18 participants, 14 completed all 3 scans.

Arm/Group Title	Lisdexamfetamine, Then Placebo	Placebo, Then Lisdexamfetamine
Arm/Group Description	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.	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..
Period Title: First Intervention (4 Weeks)
STARTED	11	7
COMPLETED	8	7
NOT COMPLETED	3	0
Period Title: First Intervention (4 Weeks)
STARTED	8	7
COMPLETED	8	7
NOT COMPLETED	0	0
Period Title: First Intervention (4 Weeks)
STARTED	8	7
COMPLETED	7	7
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	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.
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 100%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	53.5
Sex: Female, Male (Count of Participants)
Female	18 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	18 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 5.6%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 22.2%
White	12 66.7%
More than one race	1 5.6%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Blood Oxygen Level Dependent (BOLD) Signal
Description	Blood-oxygen-level dependent contrast imaging, or BOLD-contrast imaging, is a method used in functional magnetic resonance imaging (fMRI) to observe different areas of the brain or other organs, which are found to be active at any given time. BOLD signals were compared from baseline, first intervention and second intervention.
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

All participants who completed all phases of the study were included in the outcome analysis.

Arm/Group Title	Lisdexamfetamine	Placebo
Arm/Group Description	Lisdexamfetamine or Vyvanse Lisdexamfetamine: The overall objective of this study is to assess the effects of LDX on brain activation patterns during tasks of sustained attention and working memory in menopausal women.	Placebo pill, capsules Placebo: To assess the effects of a placebo pill on brain activation patterns during tasks of sustained attention and working memory in menopausal women.
Measure Participants	14	14
Mean (Standard Deviation) [percent change]	0.41 (0.65)	-0.11 (0.46)

2. Secondary Outcome

Title	Change in BADDS Total Score
Description	The total BADDS ranged from 0-120 with higher scores meaning greater problems with memory, attention and focus. Difference in BADDS score from Baseline to End of Treatment for each study Arm was calculated.
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

Participants who completed all 3 scans.

Arm/Group Title	Lisdexamfetamine	Placebo
Arm/Group Description	14 participants completed all 3 scans.	14 participants completed all 3 scans.
Measure Participants	14	14
Mean (Standard Deviation) [change in units]	-23.36 (11.57)	-8.57 (12.51)

Adverse Events

Arm/Group Title	Lisdexamfetamine		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Lisdexamfetamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Lisdexamfetamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Lisdexamfetamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/15 (6.7%)		1/15 (6.7%)
Cardiac disorders
Increase heart rate	1/15 (6.7%)	1	0/15 (0%)	0
Increase blood pressure	0/15 (0%)	0	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.