Cognitive Impairments, Symptomatic Menopause
Conditions
Keywords
Menopause, Aging, Memory, Women
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.
Interventions
DRUGLisdexamfetamine
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).
DRUGPlacebo
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.
Sponsors
Shire
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 60 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
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 details
Of the 55 who were consented for screening, 20 did not meet inclusion criteria and of the remaining 35, 32 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants were randomized to receive either Lisdexampethamine in titrated doses (20mg/d- 60mg/d) or Placebo tablets (matching Lisdexamphetamine). | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention (4 Weeks) | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 53.1 years STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 22 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 6 / 32 | 1 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
Brown Attention Deficit Disorder Scale (BADDS)
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Brown Attention Deficit Disorder Scale (BADDS) | 35.7 units on a scale | Standard Deviation 16.8 |
| Lisdexamfetamine | Brown Attention Deficit Disorder Scale (BADDS) | 21.2 units on a scale | Standard Deviation 16.8 |
| Sugar Pill | Brown Attention Deficit Disorder Scale (BADDS) | 29.8 units on a scale | Standard Deviation 17.7 |
Secondary
NYU Paragraph Recall Task
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)
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Baseline | NYU Paragraph Recall Task | Immediate paragraph recall B | 6.38 units on a scale | Standard Deviation 2.12 |
| Baseline | NYU Paragraph Recall Task | Delayed paragraph recall B | 7.81 units on a scale | Standard Deviation 3.58 |
| Baseline | NYU Paragraph Recall Task | Immediate paragraph recall A | 7.09 units on a scale | Standard Deviation 2.56 |
| Baseline | NYU Paragraph Recall Task | Delayed paragraph recall A | 4.68 units on a scale | Standard Deviation 2.65 |
| Lisdexamfetamine | NYU Paragraph Recall Task | Delayed paragraph recall B | 9.77 units on a scale | Standard Deviation 3.53 |
| Lisdexamfetamine | NYU Paragraph Recall Task | Delayed paragraph recall A | 5.90 units on a scale | Standard Deviation 3.38 |
| Lisdexamfetamine | NYU Paragraph Recall Task | Immediate paragraph recall B | 7.45 units on a scale | Standard Deviation 3.2 |
| Lisdexamfetamine | NYU Paragraph Recall Task | Immediate paragraph recall A | 7.48 units on a scale | Standard Deviation 2.63 |
| Sugar Pill | NYU Paragraph Recall Task | Delayed paragraph recall B | 8.47 units on a scale | Standard Deviation 2.97 |
| Sugar Pill | NYU Paragraph Recall Task | Immediate paragraph recall A | 7.00 units on a scale | Standard Deviation 2.7 |
| Sugar Pill | NYU Paragraph Recall Task | Immediate paragraph recall B | 6.75 units on a scale | Standard Deviation 2.53 |
| Sugar Pill | NYU Paragraph Recall Task | Delayed paragraph recall A | 4.94 units on a scale | Standard Deviation 3.02 |
Secondary
Penn Continuous Performance Test
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)
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Baseline | Penn Continuous Performance Test | 53.29 units on a scale | Standard Deviation 3.78 |
| Lisdexamfetamine | Penn Continuous Performance Test | 56.37 units on a scale | Standard Deviation 3.59 |
| Sugar Pill | Penn Continuous Performance Test | 56.21 units on a scale | Standard Deviation 3.27 |