Phase 3 Randomized Placebo Controlled Clinical Trial of Donepezil

  • STATUS
    Recruiting
  • days left to enroll
    8
  • participants needed
    276
  • sponsor
    Wake Forest University Health Sciences
Updated on 1 November 2020
Investigator
Karen Craver
Primary Contact
Kaiser Permanente-Walnut Creek (0.7 mi away) Contact
+256 other location
cancer
breast cancer
deficit
anxiolytics
hormone therapy
invasive breast cancer
antidepressants
psychotropic drugs
ssri
donepezil
memory impairment
aricept
psychotropic
psychoactive agents

Summary

This study is to compare the safety and effects of donepezil (Aricept) for patients reporting cognitive or memory issues after receiving chemotherapy for breast cancer. Patients will receive either donepezil or placebo for 24 weeks. The primary objective is to see if memory improves with the use of donepezil during the study.

Description

Randomized, double-blind, placebo-controlled study with 24 weeks of exposure to drug or placebo followed by a 12 week wash-out period. 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. A total of 276 patients will be enrolled (138 per arm). We expect an accrual rate of 7-10 participants per month based on our prior feasibility study. We expect the study to be complete within 40 months.

Participants will be asked to take one 5mg tablet of donepezil or one tablet of matching placebo orally once a day for 6 weeks followed by two 5mg tablets (10mg total) of donepezil or two placebo tablets orally once a day for 18 weeks. After 24 weeks, participants will begin a 12 week wash-out period.

Time points for performing study assessments. Participants will be administered the cognitive battery of tests and questionnaires at baseline, week 12, week 24 and week 36. In addition, a single vial of blood will be drawn at baseline for APOE genotyping and subsequent bioassays (pending supplemental funding).

Details
Treatment Placebo, Donepezil 5 mg
Clinical Study IdentifierNCT02822573
SponsorWake Forest University Health Sciences
Last Modified on1 November 2020

Adding a note
adding personal notes guide

Select a piece of text and start making personal notes.

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 75 yrs?
Are you female?
Do you have any of these conditions: Memory impairment or Cognitive Dysfunction?
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. Patients who were previously on one of these psychotropic medications and have subsequently discontinued the drug must have been off the medication for at least 4 weeks prior to enrollment. Patients who have been on a psychotropic medication for at least 12 weeks but have recently switched to a medicine in the same class (for example, switching from one SSRI antidepressant to a different SSRI antidepressant) need to be on a stable dose of the new medication for at least 4 weeks prior to enrollment to be eligible
Self-reported cognitive problem plus a measured memory deficit (score <7 on single trial of Eligibility Pre-screen HVLT-R Form 3)
ECOG performance status 0-2
Ability to understand and the willingness to sign a written informed consent document
Must be able to speak English
Patients currently taking a moderate risk QTc prolongation medication (see Appendix A) are allowed if one of the following criteria are met: 1) The moderate risk QTc prolongation medication is stopped. The patient should be off the moderate risk QTc prolongation medication for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk QTc prolongation medication must have a normal QTc interval ( 460 milliseconds) on a screening ECG following informed consent and prior to study enrollment. These patients will also be monitored at designated study follow-up visits per Section 7.5 (monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase with ECG's to assess the QTc interval; the QTc level must be 500 milliseconds at these time points in order to continue on the study drug). 3) Moderate risk QTc prolongation medications that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible
Patients currently taking a moderate risk bradycardia-causing agent (see Appendix B) are allowed if one of the following criteria are met: 1) The moderate risk bradycardia-causing agent is stopped. The patient should be off the moderate risk bradycardia-causing agent for at least 5 half-lives before starting study drug. 2) Patients that continue using a moderate risk bradycardia-causing agent must have a resting heart rate 55 beats per minute at screening following informed consent. These patients' resting heart rate will be monitored 3-7 days after initiating study drug, at week 3, and 3-7 days after the study drug dose increase per Section 7.5. 3) Moderate risk bradycardia-causing agents that are only taken occasionally may be stopped at the discretion of the treating site physician. Patients must be off medication for at least 5 half-lives prior to starting study drug to be eligible

Exclusion Criteria

Evidence or suspected recurrent or metastatic disease
Prior brain irradiation is not allowed
Planned therapy (surgery, radiation, chemotherapy, or immunotherapy) while on the study for brain and/or extracranial primary/metastatic disease
Hypersensitivity to donepezil or piperidine derivatives
Current use of ceritinib
Current use of Succinylcholine/Acetylcholinesterase Inhibitors(as listed in Appendix C). For patients who have used these medications, they must not have used them within 4 weeks prior to enrollment
Current use of high-risk QTc prolonging medication(s). See Appendix D
Current use of quinidine or systemic ketoconazole (topical ketoconazole is acceptable to use while on study)
History of dementia, Alzheimer's disease, multi-infarct dementia or clinically significant Cerebrovascular Accident (history of transient ischemic attack (TIA) is allowed)
Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drug(s). For patients who have used these medications, they must not have used them within 4 weeks prior to pre-screening. Patients who plan to start taking a cognition enhancing drug while on this study are also excluded
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
Major medical conditions that affect cognition, 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
Patients with a resting heart rate less than 55 beats per minute, seizure disorder or peptic ulcer disease (PUD)
History of congenital long QT syndrome or torsades de pointes
Screening QTc of > 460 milliseconds will make the patient ineligible
Pregnant women are excluded from this study. Following informed consent, women of child-bearing potential will be screened with a serum or urine pregnancy test within 10 days of enrollment. 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
On another intervention study involving medication at the time of enrollment or during participation in this study. (Exception: Patients will remain eligible for this study if they are also enrolled on the Alliance for Clinical Trials in Oncology study (NCT02927249): Aspirin in Preventing Recurrence of Cancer in Patients with HER2 Negative Stage II-III Breast Cancer After Chemotherapy, Surgery, and/or Radiation Therapy. Studies that involve only blood draws or questionnaires are also permitted.)
Use of investigational drugs likely to affect cognition within 30 days prior to pre-screening visit
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.
Step 2 Get screened

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more
Step 3 Enroll in the clinical study

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more
Step 4 Get your study results

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

Study

user name

Annotated by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No made yet