Expired Study
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New Haven, Connecticut 06511


Purpose:

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).


Study summary:

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.


Criteria:

Inclusion Criteria: - 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). Exclusion Criteria: - 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.


Study is Available At:


Original ID:

0403026533


NCT ID:

NCT00611533


Secondary ID:


Study Acronym:


Brief Title:

Placebo Controlled Study of Atomoxetine in the Treatment of Mild to Moderate Cognitive Difficulties in Menopausal Women


Official Title:

A Controlled Trial of Atomoxetine in the Treatment of Mild to Moderate Cognitive Difficulties in Menopausal Women


Overall Status:

Completed


Study Phase:

N/A


Genders:

Female


Minimum Age:

45 Years


Maximum Age:

60 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Pennsylvania


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Randomized, Endpoint Classification: E


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

16


Enrollment Type:

Actual


Overall Contact Information

Official Name:Cynthia N Epperson, MD
Principal Investigator
Yale University School of Medicine Department of Psychiatry

Study Dates

Start Date:May 2004
Completion Date:April 2008
Completion Type:Actual
Primary Completion Date:April 2008
Primary Completion Type:Actual
Verification Date:December 2016
Last Changed Date:January 3, 2017
First Received Date:January 29, 2008

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Brown Attention Deficit Disorder Scale (BADDS)-Adult Version total score and cluster scores from the women participating in this study will be compared to those from an age-matched sample of women with ADD (historical sample).
Time Frame:16 weeks
Safety Issues:False
Outcome Type:Primary Outcome
Measure:Women will have a reduction in score on the Brown Attention Deficit Disorder Scale and will perform better on measures of verbal memory and fluency as well as concentration and attention during ATX administration compared to placebo (PBO) administration.
Time Frame:16 weeks
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:atomoxetine
Description:Twenty subjects will be 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 tr
Arm Name:A
Other Name:Strattera
Intervention Type:Drug
Name:placebo
Description:placebo
Arm Name:P

Study Arms

Study Arm Type:Placebo Comparator
Arm Name:P
Study Arm Type:Active Comparator
Arm Name:A

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:University of Pennsylvania
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Eli Lilly and Company

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Zandi 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.
PMID:12413371
Reference Type:Reference
Citation:Wise 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. Review.
PMID:10368769
Reference Type:Reference
Citation:Shumaker 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.
PMID:12771112
Reference Type:Reference
Citation:Sherwin BB. Estrogen and cognitive functioning in women. Proc Soc Exp Biol Med. 1998 Jan;217(1):17-22. Review.
PMID:9421202
Reference Type:Reference
Citation: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.
PMID:11182481

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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