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Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil - WF 97116

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ClinicalTrials.gov Identifier: NCT02822573
Recruitment Status : Recruiting
First Posted : July 4, 2016
Last Update Posted : July 16, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:
This study is to compare the safety and effects of donepezil (Aricept) or if it decreases memory loss after receiving chemotherapy for breast cancer.

Condition or disease Intervention/treatment Phase
Cognitive Dysfunction Memory Impairment Drug: Donepezil 5 mg Drug: Placebo Phase 3

Detailed Description:
A randomized, placebo controlled, double-blind, parallel group Phase 3 design will be used to assess the effect of 24 weeks of donepezil on cognitive function (memory) in breast cancer survivors who report having cognitive dysfunction and demonstrate memory impairment 1-5 year post chemotherapy. Patients who meet the eligibility criteria will be stratified by age (<50, 50-59, 60-69, ≥70) and randomized to donepezil or placebo with equal probability.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil in Chemotherapy Exposed Breast Cancer Survivors With Cognitive Impairment
Actual Study Start Date : May 30, 2017
Estimated Primary Completion Date : October 12, 2020
Estimated Study Completion Date : October 12, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Memory

Arm Intervention/treatment
Active Comparator: Donepezil 5 mg
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Drug: Donepezil 5 mg
Participants will be asked to take one 5 mg tablet of donepezil daily for 6 weeks followed by two 5mg tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Other Name: Aricept

Placebo Comparator: Matching Placebo
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Drug: Placebo
Participants will be asked to take one tablet of matching placebo daily for 6 weeks followed by two tablets daily for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.
Other Name: Sugar Pill




Primary Outcome Measures :
  1. Memory Question [ Time Frame: Pre-Screening ]
    Prospective participants will first be asked, "How would you rate the change in your ability to think including remembering, organizing your thoughts and speaking since you were first diagnosed with cancer?" Response choices will be 'No change or better', 'mildly worse', 'moderately worse', 'much worse'. Only if a woman responds with "moderately worse" or "much worse" will she proceed.

  2. HVLT- R Form C 1st learning trial [ Time Frame: Pre-Screening ]
    An entry level score of < 7 words recalled is required. This will provide information on ineligible patients and patients that are eligible and choose not to participate.

  3. Changes in Hopkins Verbal Learning Test-Revised (HVLT-R) Results [ Time Frame: Baseline and Week 12 ]
    The HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R.

  4. Changes in Controlled Oral Word Association Test (COWA) Results [ Time Frame: Baseline and Week 12 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  5. Changes in Trail Making Test, Parts A & B (TMT-A, TMT-B) Results [ Time Frame: Baseline and Week 12 ]
    Part A of the TMT measures attention and visual motor skills and processing speed and requires subjects to connect 25 numbered circles in the proper sequence (1-2-3-…) as quickly as possible. TMT-B is similar except subjects are required to connect dots in an alternating numerical and alphabetical sequence (1-A-2-B-…). TMT-B with its added complexity and set shifting requirements is a widely used measure of executive function. The score for TMT-A and TMT-B is the total time in seconds required to complete the task. Scores can also be generated for number of errors and number of circles correctly connected.

  6. Shipley Institute of Living Scale-Version 2 Vocabulary [ Time Frame: Baseline ]
    Provides an assessment of premorbid intellectual functioning comparable to a verbal IQ and thus is a proxy for cognitive reserve. This vocabulary test requires respondents to read a target word and select one of four words that most closely means the same thing. Score it total correct of 40 items.

  7. Changes in PROMIS 7-item Fatigue Scale Results [ Time Frame: Baseline and Week 12 ]
    This self-report scale assesses fatigue.

  8. PROMIS 8-item Sleep Disturbance Scale [ Time Frame: Baseline ]
    Self-reported sleep disturbance will be measured with the PROMIS Sleep Disturbance scale.

  9. Changes in Personal Health Questionnaire-9 Depression Scale Results [ Time Frame: Baseline, Week 12, Week 24, Week 36 ]
    The PHQ-9 is a widely used self-report scale for assessing depression severity. It has 9 items assessing cardinal features of major depression which are rated from zero ("Not at all") to 5 ("nearly every day").

  10. Digit Span Test-Backwards (DST-B) [ Time Frame: Baseline ]
    The DST-B assesses attention and working memory. It requires respondents to repeat back in reverse order spans of numbers. Seven pairs of spans of increasing lengths are presented and repeated. A total score is the number of correctly repeated spans.

  11. Changes in Hopkins Verbal Learning Test-Revised (HVLT-R) Results [ Time Frame: Baseline, Week 12 and Week 24 ]
    The HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R.

  12. Changes in Hopkins Verbal Learning Test-Revised (HVLT-R) Results [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ]
    The HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R.

  13. Changes in Controlled Oral Word Association Test (COWA) Results [ Time Frame: Baseline, Week 12 and Week 24 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  14. Changes in Controlled Oral Word Association Test (COWA) Results [ Time Frame: Baseline, and Week 12, Week 24 and Week 36 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  15. Changes in Trail Making Test, Parts A & B (TMT-A, TMT-B) Results [ Time Frame: Baseline, Week 12 and Week 24 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  16. Changes in Trail Making Test, Parts A & B (TMT-A, TMT-B) Results [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  17. Changes in Shipley Institute of Living Scale-Version 2 Vocabulary Results [ Time Frame: Baseline and Week 12 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  18. Changes in Shipley Institute of Living Scale-Version 2 Vocabulary Results [ Time Frame: Baseline, Week 12, and Week 24 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  19. Changes in Shipley Institute of Living Scale-Version 2 Vocabulary Results [ Time Frame: Baseline, Week 12, Week 24, and Week 36 ]
    The COWA measures speed of mental processing, verbal fluency, and executive function. Subjects are asked to name as many words as possible all beginning with a specified letter. A total of three trials are administered, each with a different letter (F-A-S). The score on the COWA is the total number of words named across the three trials minus repetitions.

  20. Changes in PROMIS 7-item Fatigue Scale Results [ Time Frame: Baseline, Week 12 and Week 24 ]
    This self-report scale assesses fatigue.

  21. Changes in PROMIS 7-item Fatigue Scale Results [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ]
    This self-report scale assesses fatigue.

  22. Changes in PROMIS 8-item Sleep Disturbance Scale Results [ Time Frame: Baseline and Week 12 ]
    Self-reported sleep disturbance will be measured with the PROMIS Sleep Disturbance scale.

  23. Changes in PROMIS 8-item Sleep Disturbance Scale Results [ Time Frame: Baseline, Week 12 and Week 24 ]
    Self-reported sleep disturbance will be measured with the PROMIS Sleep Disturbance scale.

  24. Changes in PROMIS 8-item Sleep Disturbance Scale Results [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ]
    Self-reported sleep disturbance will be measured with the PROMIS Sleep Disturbance scale.

  25. Changes in Digit Span Test-Backwards (DST-B) Results [ Time Frame: Baseline and Week 12 ]
    The DST-B assesses attention and working memory. It requires respondents to repeat back in reverse order spans of numbers. Seven pairs of spans of increasing lengths are presented and repeated. A total score is the number of correctly repeated spans.

  26. Changes in Digit Span Test-Backwards (DST-B) Results [ Time Frame: Baseline, Week 12 and Week 24 ]
    The DST-B assesses attention and working memory. It requires respondents to repeat back in reverse order spans of numbers. Seven pairs of spans of increasing lengths are presented and repeated. A total score is the number of correctly repeated spans.

  27. Changes in Digit Span Test-Backwards (DST-B) Results [ Time Frame: Baseline, Week 12, Week 24 and Week 36 ]
    The DST-B assesses attention and working memory. It requires respondents to repeat back in reverse order spans of numbers. Seven pairs of spans of increasing lengths are presented and repeated. A total score is the number of correctly repeated spans.


Secondary Outcome Measures :
  1. Changes in Digit Span Test-Backwards (DST-B) Results [ Time Frame: Baseline, Week 12, Week 24, Week 36 ]
    The DST-B assesses attention and working memory. It requires respondents to repeat back in reverse order spans of numbers. Seven pairs of spans of increasing lengths are presented and repeated. A total score is the number of correctly repeated spans.

  2. Changes in Digit Symbol Coding Results [ Time Frame: Baseline, Week 12, Week 24, Week 36 ]
    The DSC test measures processing speed. It requires respondents to transcribe symbols (e.g., >) associated with a number (0-9) into empty boxes beneath a series of randomly ordered numbers. Total score is number of correctly transcribed symbols in 2 minutes. Scores range from 0-133.

  3. Changes in PROMIS 7-item Fatigue Scale Results [ Time Frame: Baseline, Week 12, Week 24, Week 36 ]
    This self-report scale assesses fatigue.

  4. Changes in PROMIS 8-item Sleep Disturbance Scale Results [ Time Frame: Baseline, Week 12, Week 24, Week 36 ]
    Self-reported sleep disturbance will be measured with the PROMIS Sleep Disturbance scale.

  5. Changes in Hopkins Verbal Learning Test-Revised (HVLT-R) Results [ Time Frame: Baseline, Week 12, Week 24, Week 36 ]
    The HVLT-R measures verbal learning and memory. It consists of a 12-item word list which is read to subjects on three successive learning trials. Free recall scores are recorded for each learning trial. Scores for immediate recall (total of three trials), delayed recall (total number of words recalled after 20 minutes), and recognition (total number of words correctly identified) will be the variables derived from the HVLT-R.

  6. Changes in FACT-Cognition (Version 3) Results [ Time Frame: Baseline, Week 12, Week 24, and Week 36 ]
    This is a validated self-report questionnaire that assesses patients' perceptions of their cognitive function and the impact of cognitive problems on overall quality of life over the prior 7 days. Higher scores reflect better cognitive functioning and less impairment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women ≥18 years old with history of invasive breast cancer
  • Must have completed at least 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy between 1 and 5 years prior to registration (Ongoing herceptin or other chronic HER 2 directed therapies are allowed).
  • Patients receiving ongoing hormonal therapy for breast cancer must be on the same hormonal agent for at least 3 months prior to study registration and plan to continue for the duration of the study (9 months)
  • Use of psychotropic medications (anti-depressants, anxiolytics, sleeping aids, narcotics) is permitted (patient will be asked to list any that have been taken within the last 3 days on the recent medication sheet) if dose is stable over previous 12 weeks.
  • Self-reported cognitive problem plus a measured memory deficit (score <7 on single trial of Eligibility Pre-screen HVLT-R Form C).
  • Prior treatment with > 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy
  • ECOG performance status 0-2
  • Ability to understand and the willingness to sign a written informed consent document.
  • Must be able to speak English.

Exclusion Criteria:

  • Evidence or suspected recurrent or metastatic disease. Prior brain irradiation is not allowed.
  • Patients may not currently be taking Ketoconazole or Quinidine
  • History of dementia, Alzheimer's disease, multi-infarct dementia or CVA (history of transient ischemic attack (TIA is allowed).
  • Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drugs are not allowed. For patients who have used these medications they must not have used them within 4 weeks prior to registration.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to donepezil. Hypersensitivity to donepezil.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, recent myocardial infarction, cardiac arrhythmia.
  • Traumatic brain injury, multiple sclerosis, acute severe fatigue, chronic fatigue syndrome or fibromyalgia.
  • Psychiatric illness/social situations that would limit compliance with study requirements including but not limited to a history of schizophrenia, psychosis or substance abuse.
  • Untreated current severe depression. Currently treated depression is permitted if treatment is stable.
  • Pregnant women are excluded from this study. The effects of donepezil on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because donepezil is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
  • It is unknown whether donepezil is excreted in breast milk, for this reason women who are currently breast-feeding are not eligible for this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02822573


Contacts
Contact: Tammy Vogler, RN (336) 713-6907 tvogler@wakehealth.edu

Locations
United States, North Carolina
Wake Forest School of Medicine Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Tammy Vogler, RN    336-713-6907    tvogler@wakehealth.edu   
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
Principal Investigator: Stephen R Rapp, PhD Wake Forest University Health Sciences

Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02822573     History of Changes
Other Study ID Numbers: IRB00019792
3UG1CA189824-04S1 ( U.S. NIH Grant/Contract )
REBAWF 97116 ( Other Identifier: NCI )
First Posted: July 4, 2016    Key Record Dates
Last Update Posted: July 16, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents