MenopauseNCT00611533
Placebo Controlled Study of Atomoxetine in the Treatment of Mild to Moderate Cognitive Difficulties in Menopausal Women
A study testing atomoxetine in people with Menopause and Cognitive Disturbances, run by University of Pennsylvania at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 45 to 60 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Menopause, Cognitive Disturbances
- What is being tested?
- atomoxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- May 2004to Apr 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 60 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Menopausal subjects between the ages of 45 and 60 years;
- Physically healthy with no major medical illnesses;
- No history within the past 5 years of a DSM-IV psychiatric or substance abuse diagnosis by structured diagnostic interview (SCID);
- Subjects will be determined to be either peri or post-menopausal;
- Subjects must be within 5 years of their last menstrual period;
- Subjective report of cognitive disturbances of at least mild to moderate severity;
- All subjects must be of at least average intelligence as determined using the Wechsler Abbreviated Scale of Intelligence (WASI).
Who cannot join
- Clinical evidence of dementia and/or signs of dementia on the Mini-Mental Status Exam (MMSE score of <22);
- History of familial dementia;
- Use of any psychotropic medication within the previous 6 months;
- Use of any estrogen replacement therapy within the previous 6 months;
- Current pregnancy;
- Signs of an unstable medical or neurological disorder.
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale University School of Medicine
New Haven, Connecticut, 06511
About this study
Official title: A Controlled Trial of Atomoxetine in the Treatment of Mild to Moderate Cognitive Difficulties in Menopausal Women
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).
Read the detailed description
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.
- Conditions
- Menopause, Cognitive Disturbances
- Being tested
- atomoxetine, placebo
- Keywords
- Menopause, Cognition
- Medical subject headings
- Cognition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atomoxetineDrug
Also called Strattera
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.
placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Atomoxetine | Active comparator | 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. Receives: Drug: atomoxetine |
| Placebo | Placebo comparator | 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. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline and after 6 weeks intervention
Secondary outcomes (3)
Blood Pressure
Measured: Baseline and after 6 weeks intervention
Heart Rate
Measured: Baseline and after 6 weeks intervention
Weight
Measured: Baseline and after 6 weeks intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2008 (estimated)
- Study startMay 2004
- Primary completionApr 2008
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for MenopauseStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Cynthia N Epperson, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00611533
- Sponsor's protocol ID
- 0403026533
- Status last verified
- Mar 2017
- First submitted
- 29 Jan 2008
- Last updated
- 17 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jezierski MK, Sohrabji F. Neurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation. Neurobiol Aging. 2001 Mar-Apr;22(2):309-19. doi: 10.1016/s0197-4580(00)00230-x.
PubMed 11182481Sherwin BB. Estrogen and cognitive functioning in women. Proc Soc Exp Biol Med. 1998 Jan;217(1):17-22. doi: 10.3181/00379727-217-44200.
PubMed 9421202Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J; WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003 May 28;289(20):2651-62. doi: 10.1001/jama.289.20.2651.
PubMed 12771112Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL. Neuroendocrine influences and repercussions of the menopause. Endocr Rev. 1999 Jun;20(3):243-8. doi: 10.1210/edrv.20.3.0364.
PubMed 10368769Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JC; Cache County Memory Study Investigators. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA. 2002 Nov 6;288(17):2123-9. doi: 10.1001/jama.288.17.2123.
PubMed 12413371
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Controlled Trial of Atomoxetine in the Treatment of Mild to Moderate Cognitive Difficulties in Menopausal Women
- ClinicalTrials.gov ID
- NCT00611533
- Acronym / sponsor ID
- 0403026533
- Conditions
- Menopause, Cognitive Disturbances
- Keywords
- Menopause, Cognition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- May 2004
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Posted 3 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atomoxetine | Active comparator | Drug: atomoxetineSubjects 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. |
| Placebo | Placebo comparator | Drug: placeboSubjects 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. |
Who may qualify
- Ages
- 45 to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Menopausal subjects between the ages of 45 and 60 years;
- Physically healthy with no major medical illnesses;
- No history within the past 5 years of a DSM-IV psychiatric or substance abuse diagnosis by structured diagnostic interview (SCID);
- Subjects will be determined to be either peri or post-menopausal;
- Subjects must be within 5 years of their last menstrual period;
Key exclusion criteria (6 listed)
- Clinical evidence of dementia and/or signs of dementia on the Mini-Mental Status Exam (MMSE score of <22);
- History of familial dementia;
- Use of any psychotropic medication within the previous 6 months;
- Use of any estrogen replacement therapy within the previous 6 months;
- Current pregnancy;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| atomoxetineAlso: StratteraSubjects 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. | Drug | Atomoxetine |
| placeboSubjects 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. | Drug | Placebo |
Primary outcome
Brown Attention Deficit Disorder Scale
Time frame: Baseline and after 6 weeks intervention
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.
BADDS Total Score
Time frame: Baseline and after 6 weeks intervention
The total BADDS ranged from 0-120 with higher scores meaning greater problems with memory, attention and focus.
3 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11182481Jezierski MK, Sohrabji F. Neurotrophin expression in the reproductively senescent forebrain is refractory to estrogen stimulation. Neurobiol Aging. 2001 Mar-Apr;22(2):309-19. doi: 10.1016/s0197-4580(00)00230-x.
- Background: PubMed 9421202Sherwin BB. Estrogen and cognitive functioning in women. Proc Soc Exp Biol Med. 1998 Jan;217(1):17-22. doi: 10.3181/00379727-217-44200.
- Background: PubMed 12771112Shumaker SA, Legault C, Rapp SR, Thal L, Wallace RB, Ockene JK, Hendrix SL, Jones BN 3rd, Assaf AR, Jackson RD, Kotchen JM, Wassertheil-Smoller S, Wactawski-Wende J; WHIMS Investigators. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003 May 28;289(20):2651-62. doi: 10.1001/jama.289.20.2651.
- Background: PubMed 10368769Wise PM, Smith MJ, Dubal DB, Wilson ME, Krajnak KM, Rosewell KL. Neuroendocrine influences and repercussions of the menopause. Endocr Rev. 1999 Jun;20(3):243-8. doi: 10.1210/edrv.20.3.0364.
- Background: PubMed 12413371Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC, Breitner JC; Cache County Memory Study Investigators. Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study. JAMA. 2002 Nov 6;288(17):2123-9. doi: 10.1001/jama.288.17.2123.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cynthia N Epperson, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing atomoxetine in people with Menopause and Cognitive Disturbances, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brown Attention Deficit Disorder Scale (time frame: Baseline and after 6 weeks intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00611533, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2017.