Attention & Memory Impairments in Menopausal Women

• ClinicalTrials.gov Identifier: NCT01324024
• Recruitment Status: Completed
• First Posted: March 28, 2011
• Results First Posted: June 28, 2017
• Last Update Posted: June 28, 2017
• Sponsor: University of Pennsylvania
• Collaborator: Shire
• Information provided by (Responsible Party): University of Pennsylvania

Tracking Information

• First Submitted Date: March 24, 2011
• First Posted Date: March 28, 2011
• Results First Submitted Date: May 11, 2016
• Results First Posted Date: June 28, 2017
• Last Update Posted Date: June 28, 2017
• Study Start Date: May 2011
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 25, 2017)

Brown Attention Deficit Disorder Scale (BADDS) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: March 25, 2011)

Brown Attention Deficit Disorder Scale [ Time Frame: 10 weeks ]

The primary objective of this study is to reduce subjective symptoms of executive function impairment in peri and early postmenopausal women who are concerned about their "memory" and/or "cognition." Subjective assessment of executive functioning such as a sustained attention, focus, organization, working memory and motivation for work/activities will be assessed with our primary outcome variable, the Brown Attention Deficit Disorder Scale (BADDS; Brown, 1996, Harcourt Brace & Co.).

Current Secondary Outcome Measures (submitted: May 25, 2017)

• Penn Continuous Performance Test [ Time Frame: 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.
• NYU Paragraph Recall Task [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: March 25, 2011)

Cognitive Tasks [ Time Frame: 10 weeks ]

The secondary objective of this study is to determine whether LDX improves performance on objective measures of sustained attention, verbal recall and working memory. This will be measured using a battery of cognitive tasks aimed at assessing sustained attention, verbal encoding and recall, and verbal working memory. These tasks include the STROOP test; NYU Paragraph Recall Test; Spatial Span Forward and Spatial Span Backward from the Wechsler Memory Scale; 3-Back Task; and Verbal Paired Associates II.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Attention & Memory Impairments in Menopausal Women
• Official Title: Attention & Memory Impairments in Menopausal Women: A Possible Role for Vyvanse?
• 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.

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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Symptomatic Menopause
• Cognitive Impairments

Intervention

• 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 Name: 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.

Study Arms

• 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.
  Interventions:

  • Drug: Lisdexamfetamine
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: Lisdexamfetamine
  • Drug: Placebo

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.
• Epperson CN, Shanmugan S, Kim DR, Mathews S, Czarkowski KA, Bradley J, Appleby DH, Iannelli C, Sammel MD, Brown TE. New onset executive function difficulties at menopause: a possible role for lisdexamfetamine. Psychopharmacology (Berl). 2015 Aug;232(16):3091-100. doi: 10.1007/s00213-015-3953-7. Epub 2015 Jun 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 25, 2017): 35
• Original Estimated Enrollment (submitted: March 25, 2011): 34
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 45 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01324024
• Other Study ID Numbers: 812470
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University of Pennsylvania
• Study Sponsor: University of Pennsylvania
• Collaborators: Shire

Investigators

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

• PRS Account: University of Pennsylvania
• Verification Date: May 2017