An interventional study of atomoxetine and placebo in Menopause and Cognitive Disturbances, sponsored by University of Pennsylvania. Completed at 1 site in United States. Open to female participants aged 45 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-04-17.
Sponsored by University of Pennsylvania · Not applicable, Interventional, and Treatment
The purpose of this study is to examine the efficacy of atomoxetine (ATX) treatment for the mild to moderate cognitive disturbances frequently experienced by women during the menopause transition. In addition, we seek to determine, using the Brown Attention Deficit Disorder Scale (BADDS), whether and to what degree peri- and early post-menopausal women experience cognitive disturbances which overlap with the impairments of executive function characteristic of adults with attention deficit disorder (ADHD).
Decline in cognitive function, and in particular memory, is a frequent complaint for which menopausal women seek clinical intervention. While there is a wealth of preclinical evidence demonstrating the neuroprotective and cognitive enhancing role of estradiol (Wise et al., 1999; Jezierski \& Sohrabji, 2001), recent publicity from the Women's Health Initiative Study has made gynecologists and menopausal women concerned about using estrogen therapy (ET) to address their cognitive complaints as well as other symptoms of menopause (WHI Writing Group, 2002). Decades of data suggesting that estrogen enhances cognitive function in women undergoing surgical or natural menopause (Sherwin et al., 1998) has been all but forgotten in the wake of the results of the WHI. Further, recent findings from a naturalistic study suggesting that having used estrogen replacement therapy for three years before the mean age of 70 years significantly reduced the risk of Alzheimer's Disease (AD; Zandi et al., 2002) did not receive sufficient attention in the lay press or in scientific circles to allay concerns. Most recently, conjugated equine estrogen plus medroxyprogesterone acetate (PremPro®) use daily is associated with a small increased risk for dementia (Schumaker et al., 2003).
Now that clinicians and women have become hesitant to utilize ET, they find themselves between the proverbial rock and a hard place as there have been no studies demonstrating efficacy of any other agent in the treatment of mild to moderate cognitive difficulties in healthy non-demented menopausal women. Thus, it is timely and crucial to investigate other pharmacologic strategies aimed at improving cognitive function in this population.
Interestingly, 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 (Warga, 1999; Brown, 2000). That ATX has demonstrated efficacy in the treatment of ADHD provides a compelling rationale for investigating the treatment of menopause-related declines in memory and cognitive function. Thus, this will be the first double-blind, placebo-controlled, cross-over clinical trial to obtain preliminary data for the efficacy of ATX in the treatment of mild to moderate cognitive disturbances in menopause aged women. Women who are in the early menopause have been chosen for this study as clinical and preclinical data suggest that long periods of hypoestrogenism may be associated with poorer response to intervention with ET. Therefore, we believe that this population may be more likely to respond to treatment with ATX than women who have been postmenopausal for many years.
3,843 studies on the registry are indexed under Cognitive Dysfunction; 1,100 are open to participants now.
This study's enrollment of 16 is below the median of 65 across 2,808 interventional studies indexed under Cognitive Dysfunction.
Browse Cognitive Dysfunction studies →University of Pennsylvania is the lead sponsor of 1,635 studies on the registry; 239 are open to participants now.
Of its 154 completed or terminated interventional studies of FDA-regulated products, 104 (68%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Subjects were enrolled into a double-blind, placebo-controlled cross over study where they will receive ATX 40mg/d x 1 week, then 80mg/d x 5 weeks or placebo (PBO) for 6 weeks, followed by a 4-week wash out period that is followed by an additional 6 weeks of treatment in the alternate condition. The 4-week washout period include a 4-day taper in the first week. Subjects undergo assessments of cognition, mood, and menopausal symptoms prior to randomization, after 6 weeks in the first treatment condition (ATX or PBO) and then finally after the second 6-week period of the alternate treatment condition. Subjects are monitored every other week to assess medication compliance and side effects. Subjects will be instructed to take one capsule of ATX 40mg/d or placebo per day. If tolerated, the number of pills of ATX will be increased to 2 per day at the end of Week 1 of both Trials A and B. Subjects will remain on two capsules per day for the remaining 5 weeks of Trials A and B.
Drug: atomoxetine
Subjects were enrolled into a double-blind, placebo-controlled cross over study where they will receive ATX 40mg/d x 1 week, then 80mg/d x 5 weeks or placebo (PBO) for 6 weeks, followed by a 4-week wash out period that is followed by an additional 6 weeks of treatment in the alternate condition. The 4-week washout period include a 4-day taper in the first week. Subjects undergo assessments of cognition, mood, and menopausal symptoms prior to randomization, after 6 weeks in the first treatment condition (ATX or PBO) and then finally after the second 6-week period of the alternate treatment condition. Subjects are monitored every other week to assess medication compliance and side effects. Subjects will be instructed to take one capsule of ATX 40mg/d or placebo per day. If tolerated, the number of pills of ATX will be increased to 2 per day at the end of Week 1 of both Trials A and B. Subjects will remain on two capsules per day for the remaining 5 weeks of Trials A and B.
Drug: placebo
Subjects will receive ATX 40mg/d x 1 week, then 80mg/d x 5 weeks followed by a 4-week wash out period that is followed by an additional 6 weeks of treatment in the alternate condition. The 4-week washout period include a 4-day taper in the first week.
Also known as: Strattera
Subjects will receive placebo equivalent for 6 weeks followed by a 4-week wash out period that is followed by an additional 6 weeks of treatment in the alternate condition. The 4-week washout period include a 4-day taper in the first week.
Brown Attention Deficit Disorder Scale
Raw scores for 5 clusters (organizing/activating, attention/concentration, alertness/effort/processing, managing affect interference, and working memory/recall) on the BADDS were converted to T scores which range from 50-99, with higher scores meaning greater impairment.
Time frame: Baseline and after 6 weeks intervention
BADDS Total Score
The total BADDS ranged from 0-120 with higher scores meaning greater problems with memory, attention and focus.
Time frame: Baseline and after 6 weeks intervention
Blood Pressure
Time frame: Baseline and after 6 weeks intervention
Heart Rate
Time frame: Baseline and after 6 weeks intervention
Weight
Time frame: Baseline and after 6 weeks intervention
| Milestone | Atomoxetine Then Placebo | Placebo Then Atomoxetine |
|---|---|---|
| Started | 8 | 8 |
| Completed | 8 | 6 |
| Not completed | 0 | 2 |
| Withdrew: Never started study | 0 | 1 |
| Withdrew: Adverse event | 0 | 1 |
| Milestone | Atomoxetine Then Placebo | Placebo Then Atomoxetine |
|---|---|---|
| Started | 8 | 6 |
| Completed | 8 | 4 |
| Not completed | 0 | 2 |
| Withdrew: Adverse event | 0 | 2 |
Raw scores for 5 clusters (organizing/activating, attention/concentration, alertness/effort/processing, managing affect interference, and working memory/recall) on the BADDS were converted to T scores which range from 50-99, with higher scores meaning greater impairment.
| T score | Baseline | Atomoxetine | Placebo |
|---|---|---|---|
| organizing/activating | 60.7 ± 11.6 | 55.6 ± 8.9 | 56.3 ± 8.9 |
| attention/concentration | 58.8 ± 8.7 | 52.1 ± 4.0 | 56.4 ± 7.1 |
| alertness/effort/processing | 57.4 ± 10.0 | 54.2 ± 5.5 | 54.7 ± 7.9 |
| managing affect interference | 55.3 ± 7.9 | 51.8 ± 4.5 | 51.6 ± 3.8 |
| working memory/recall | 61.3 ± 10.0 | 52.4 ± 5.3 | 59.6 ± 10.3 |
The total BADDS ranged from 0-120 with higher scores meaning greater problems with memory, attention and focus.
| units on a scale | Baseline | Atomoxetine | Placebo |
|---|---|---|---|
| BADDS Total Score | 38.6 ± 20.2 | 25.5 ± 16.0 | 30.1 ± 16.0 |
| mm Hg | Baseline | Atomoxetine | Placebo |
|---|---|---|---|
| systolic BP | 118.8 ± 12.5 | 116.7 ± 11.3 | 120.3 ± 8.5 |
| diastolic BP | 74 ± 10.0 | 69.8 ± 7.7 | 70.7 ± 5.2 |
| beats/min | Baseline | Atomoxetine | Placebo |
|---|---|---|---|
| Heart Rate | 63 ± 3.2 | 68.8 ± 8.2 | 66.3 ± 5.5 |
| lb | Baseline | Atomoxetine | Placebo |
|---|---|---|---|
| Weight | 160.1 ± 41.8 | 158.1 ± 44.4 | 159.8 ± 42.6 |
Collected over Up to 16 weeks study intervention. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Atomoxetine | — | 0/16 (0%) | 2/16 (12.5%) |
| Placebo | — | 0/16 (0%) | 1/16 (6.3%) |
| Event | Atomoxetine | Placebo |
|---|---|---|
| NauseaGastrointestinal disorders | 2/16 | 1/16 |
| increase in blood pressureCardiac disorders | 1/16 | 0/16 |
| racing heartCardiac disorders | 0/16 | 1/16 |
| dry mouthGeneral disorders | 0/16 | 1/16 |
| racing thoughtsPsychiatric disorders | 0/16 | 1/16 |
| insomniaGeneral disorders | 0/16 | 1/16 |
Participants who had at least one post randomization visit.
| Age, Continuous(years) | All Study Participants |
|---|---|
| Mean | 54.0 ± 2.8 |
| Sex: Female, Male(Participants) | All Study Participants |
|---|---|
| Female | 14 |
| Male | 0 |
| Region of Enrollment(Participants) | All Study Participants |
|---|---|
| United States | 14 |
| Years of education(years) | All Study Participants |
|---|---|
| Mean | 16.4 ± 3.2 |
| Months since last menstrual period(months) | All Study Participants |
|---|---|
| Mean | 29.3 ± 20.5 |
| Follicle stimulating hormone(IU/L) | All Study Participants |
|---|---|
| Mean | 76.0 ± 33.8 |
| Estradiol(pg/mL) | All Study Participants |
|---|---|
| Mean | 31.9 ± 32.9 |
| Brown attention deficit disorder scale(units on a scale) | All Study Participants |
|---|---|
| Mean | 38.6 ± 20.2 |
1 further baseline measures are reported on the registry.
This study is completed, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.
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