Breast CancerPhase 2NCT06727773
Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer
A Phase 2 study testing Memantine and Exercise Intervention in people with Breast Cancer and Locally Advanced Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
This randomized, placebo-controlled trial aims to assess the feasibility, acceptability, and preliminary efficacy of memantine and the University of Carolina (UNC)'s Get Real \& Heel cancer exercise program (MEM+EX) in addressing cancer-related cognitive impairment (CRCI) and underlying CRCI biomarkers. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Locally Advanced Breast Cancer, Cognitive Impairment
- What is being tested?
- Memantine and Exercise Intervention
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2025to 15 Jun 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to participate in the study a subject must meet all of the eligibility criteria outlined below.
- Female
- Age ≥ 18 years at the time of consent.
- Stage I-III Breast Cancer
- Recommended chemotherapy
- Enroll prior to 3rd cycle of chemotherapy
- English-speaking
Who cannot join
- Allergy to memantine
- Previous chemotherapy (prior to the current regimen),
- Severe cognitive impairment, defined by Blessed Orientation Memory Concentration Test Score ≥11
- Myocardial infarction in the last 6 months
- Cardiovascular or orthopedic limitations to exercise
- Severe mental illness (i.e., schizophrenia or bipolar affective disorder)
Show all 9Show fewer
- Current alcohol or drug abuse
- Inability to swallow capsules </= 5mL/min
- CrCl </= 5mL/min
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27599
Zev M Nakamura, MD, zev_nakamura@med.unc.edu
Zev M Nakamura, MD
About this study
This randomized, placebo-controlled trial aims to assess the feasibility, acceptability, and preliminary efficacy of memantine and the University of Carolina (UNC)'s Get Real \& Heel cancer exercise program (MEM+EX) in addressing cancer-related cognitive impairment (CRCI) and underlying CRCI biomarkers. Ninety stage I-III breast cancer patients during chemotherapy will be randomized into three groups: MEM+EX, memantine, or placebo. The study will evaluate recruitment, retention, adherence, acceptability, cognitive function, brain-derived neurotrophic factor (BDNF), inflammatory markers, and frailty at multiple time points.
Read the detailed description
There are 4 million breast cancer survivors in the U.S. and an estimated 1.4 million suffer from long-term cognitive deficits from cancer treatment. Compared to other cancers and treatments, cognitive decline has been most robustly described in breast cancer and following chemotherapy with up to 75% self-reporting and ~50% objectively demonstrating at least mild cognitive deficits after chemotherapy. Memantine, an N-methyl-D-aspartate receptor antagonist, is a promising medication to address underlying mechanisms of CRCI, including inflammation and pathways involving brain-derived neurotrophic factor (BDNF). Exercise, a promising intervention for frailty which intervenes on multiple mechanisms of aging, is an ideal strategy to augment the targeted effects of memantine.
The primary objective of this study is to demonstrate the feasibility and acceptability of MEM+EX during breast cancer chemotherapy. Secondarily, the preliminary efficacy of MEM+EX and memantine on putative biomarkers of CRCI and cognitive function will be evaluated. Furthermore, the impact of frailty on the preliminary efficacy of MEM+EX and memantine will be explored.
The proposed study has the potential to produce significant public health benefit by filling a major gap in effective CRCI treatments. It will provide important pilot data for future, definitive randomized controlled studies. Finally, this study will advance understanding of potential targets to pursue in future cognitive interventions, including pathways involving BDNF and inflammation, during treatment for cancer.
- Conditions
- Breast Cancer, Locally Advanced Breast Cancer, Cognitive Impairment, Cognitive Decline, Cognitive Change, Breast Cancer Stage I
- Being tested
- Memantine, Placebo medication, Exercise Intervention, Exercise Control
- Keywords
- chemotherapy, memantine, placebo-controlled, exercise, Get Real & Heel cancer exercise program
- Medical subject headings
- Breast Neoplasms, Cognitive Dysfunction, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MemantineDrug
memantine capsule
Placebo medicationDrug
placebo capsule
Exercise InterventionOther
Also called Get Real & Heel
Exercise Intervention participants will concurrently engage in remotely delivered Get Real \& Heel, 3d/week. Intensity for aerobic and strength-training components will progress as tolerated under the direction of a trained exercise physiologist.
Exercise ControlOther
Also called Exercise library
Exercise control will have access to a library of pre-recorded Get Real \& Heel sessions.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Participants will receive study medication (memantine) and Get Real \& Heel exercise guided by the therapist. Receives: Drug: Memantine; Other: Exercise Intervention |
| Arm 2 | Placebo comparator | Participants have access to a library of pre-recorded Get Real \& Heel sessions. Receives: Drug: Placebo medication; Other: Exercise Control |
| Arm 3 | Experimental | Participants will receive study medication (memantine) and access to a library of pre-recorded Get Real \& Heel sessions. Receives: Drug: Memantine; Other: Exercise Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of recruitment
Rates of recruitment will be measured as a number of subjects joined the study.
Measured: Baseline
Rates of retention
Rates of retention will be measured as the proportion of subjects who remained in the study at post-intervention (up to 6 months) and after 6 months among those who started the intervention
Measured: Up to a year
Rates of adherence
Rates of adherence will be measured as a number of subjects who joined the study completed 80 percent of planned study activities.
Measured: Up to a year
The acceptability of memantine + Get Real and Heel (MEM+EX)
The acceptability of memantine + Get Real and Heel (MEM+EX) will be assessed using the Client Satisfaction Questionnaire (CSQ-3). CSQ-3 is a three-item measure of treatment acceptability that has demonstrated excellent reliability and validity across a range of patient care settings.
Each item is scored on a Likert-type scale from 1 (low satisfaction) to 4 (high satisfaction). CSQ-3 will be completed at post-intervention only (or at the time of withdrawal from the study, if applicable).
Measured: Up to 6 months
Secondary outcomes (5)
Attention and Executive Function Composite Score
The attention and executive function score is a composite of the following neuropsychological assessment measures: Digit Span, Trail Making Test Parts A\&B, Controlled Oral Word Association Test, and Animal Naming Test. It will be calculated as the sum of Z-scores (standardized based on available age-, sex-, education-, and race/ethnicity-matched normative data) of the individual subtests and range from a Z-score of -3 to +3.
Measured: Baseline and up to 1 year
Learning and Memory Composite Score
The learning and memory score is a composite of the following neuropsychological assessment measures: Hopkins Verbal Learning Test-Revised and Brief Visual Memory Test-Revised. It will be calculated as the sum of Z-scores (standardized based on available age-, sex-, education-, and race/ethnicity-matched normative data) of the individual subtests and range from a Z-score of -3 to +3.
Measured: Baseline and up to 1 year
Changes in patient-reported cognition
The impact of MEM+EX and memantine on cognitive function will be determined by examining changes in patient-reported cognition, as measured by the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog PCI) version 3, compared to placebo.
FACT-Cog PCI is a self-report measure designed to assess perceived cognitive functioning in cancer patients, particularly those experiencing chemotherapy-induced cognitive problems. It consists of 18 items and each item is rated on a 5-point Likert scale, ranging from 0 (Never) to 4 (Several times a day). The total score is obtained by summing the subscale scores. Higher scores indicate better perceived cognitive functioning.
Measured: Baseline and up to 1 year
The impact of MEM+EX and memantine on brain-derived neurotrophic factor (BDNF)
The impact of MEM+EX and memantine on putative biomarkers of CRCI will be determined by examining changes in BDNF compared to placebo.
Measured: Baseline and up to 6 months
The impact of MEM+EX and memantine on inflammatory markers
The impact of MEM+EX and memantine on putative biomarkers of CRCI will be determined by examining changes in inflammatory composite measure (TNF-alpha, IL-6, CRP) compared to placebo.
Measured: Baseline and up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2024
- Study start19 Aug 2025
- Primary completion15 Jun 2029 (estimated)
- Study completion15 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to MEM+EX (memantine + exercise), memantine, or placebo using a computer-generated randomization scheme that stratifies for an equal balance of age. All study personnel and participants will remain blinded until data collection is complete.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Zev Nakamura, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06727773
- Sponsor's protocol ID
- LCCC2425
- Other IDs
- K23AG086604
- Status last verified
- May 2026
- First submitted
- 22 Nov 2024
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Memantine and Exercise to Improve Cognitive Function and Modulate Biological Pathways of Cognitive Decline During Chemotherapy in Breast Cancer
- ClinicalTrials.gov ID
- NCT06727773
- Acronym / sponsor ID
- LCCC2425
- Conditions
- Breast Cancer, Locally Advanced Breast Cancer, Cognitive Impairment, Cognitive Decline, Cognitive Change, Breast Cancer Stage I
- Keywords
- chemotherapy, memantine, placebo-controlled, exercise, Get Real & Heel cancer exercise program
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 19 Aug 2025 (actual)
- Primary completion
- 15 Jun 2029 (estimated)
- Study completion
- 15 Jun 2029 (estimated)
- First posted
- 11 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized, placebo-controlled trial aims to assess the feasibility, acceptability, and preliminary efficacy of memantine and the University of Carolina (UNC)'s Get Real \& Heel cancer exercise program (MEM+EX) in addressing cancer-related cognitive impairment (CRCI) and underlying CRCI biomarkers. Ninety stage I-III breast cancer patients during chemotherapy will be randomized into three groups: MEM+EX, memantine, or placebo. The study will evaluate recruitment, retention, adherence, acceptability, cognitive function, brain-derived neurotrophic factor (BDNF), inflammatory markers, and frailty at multiple time points.
Detailed description
There are 4 million breast cancer survivors in the U.S. and an estimated 1.4 million suffer from long-term cognitive deficits from cancer treatment. Compared to other cancers and treatments, cognitive decline has been most robustly described in breast cancer and following chemotherapy with up to 75% self-reporting and ~50% objectively demonstrating at least mild cognitive deficits after chemotherapy. Memantine, an N-methyl-D-aspartate receptor antagonist, is a promising medication to address underlying mechanisms of CRCI, including inflammation and pathways involving brain-derived neurotrophic factor (BDNF). Exercise, a promising intervention for frailty which intervenes on multiple mechanisms of aging, is an ideal strategy to augment the targeted effects of memantine.
The primary objective of this study is to demonstrate the feasibility and acceptability of MEM+EX during breast cancer chemotherapy. Secondarily, the preliminary efficacy of MEM+EX and memantine on putative biomarkers of CRCI and cognitive function will be evaluated. Furthermore, the impact of frailty on the preliminary efficacy of MEM+EX and memantine will be explored.
The proposed study has the potential to produce significant public health benefit by filling a major gap in effective CRCI treatments. It will provide important pilot data for future, definitive randomized controlled studies. Finally, this study will advance understanding of potential targets to pursue in future cognitive interventions, including pathways involving BDNF and inflammation, during treatment for cancer.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- Participants will be randomized to MEM+EX (memantine + exercise), memantine, or placebo using a computer-generated randomization scheme that stratifies for an equal balance of age. All study personnel and participants will remain blinded until data collection is complete.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Memantine, Other: Exercise InterventionParticipants will receive study medication (memantine) and Get Real \& Heel exercise guided by the therapist. |
| Arm 2 | Placebo comparator | Drug: Placebo medication, Other: Exercise ControlParticipants have access to a library of pre-recorded Get Real \& Heel sessions. |
| Arm 3 | Experimental | Drug: Memantine, Other: Exercise ControlParticipants will receive study medication (memantine) and access to a library of pre-recorded Get Real \& Heel sessions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- In order to participate in the study a subject must meet all of the eligibility criteria outlined below.
- Female
- Age ≥ 18 years at the time of consent.
- Stage I-III Breast Cancer
- Recommended chemotherapy
Key exclusion criteria (9 listed)
- Allergy to memantine
- Previous chemotherapy (prior to the current regimen),
- Severe cognitive impairment, defined by Blessed Orientation Memory Concentration Test Score ≥11
- Myocardial infarction in the last 6 months
- Cardiovascular or orthopedic limitations to exercise
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 |
|---|---|---|
| Memantinememantine capsule | Drug | Arm 1, Arm 3 |
| Placebo medicationplacebo capsule | Drug | Arm 2 |
| Exercise InterventionAlso: Get Real & HeelExercise Intervention participants will concurrently engage in remotely delivered Get Real \& Heel, 3d/week. Intensity for aerobic and strength-training components will progress as tolerated under the direction of a trained exercise physiologist. | Other | Arm 1 |
| Exercise ControlAlso: Exercise libraryExercise control will have access to a library of pre-recorded Get Real \& Heel sessions. | Other | Arm 2, Arm 3 |
Primary outcome
Rates of recruitment
Time frame: Baseline
Rates of recruitment will be measured as a number of subjects joined the study.
Rates of retention
Time frame: Up to a year
Rates of retention will be measured as the proportion of subjects who remained in the study at post-intervention (up to 6 months) and after 6 months among those who started the intervention
Rates of adherence
Time frame: Up to a year
Rates of adherence will be measured as a number of subjects who joined the study completed 80 percent of planned study activities.
The acceptability of memantine + Get Real and Heel (MEM+EX)
Time frame: Up to 6 months
The acceptability of memantine + Get Real and Heel (MEM+EX) will be assessed using the Client Satisfaction Questionnaire (CSQ-3). CSQ-3 is a three-item measure of treatment acceptability that has demonstrated excellent reliability and validity across a range of patient care settings. Each item is scored on a Likert-type scale from 1 (low satisfaction) to 4 (high satisfaction). CSQ-3 will be completed at post-intervention only (or at the time of withdrawal from the study, if applicable).
5 secondary outcomes
Attention and Executive Function Composite Score
Time frame: Baseline and up to 1 year
Learning and Memory Composite Score
Time frame: Baseline and up to 1 year
Changes in patient-reported cognition
Time frame: Baseline and up to 1 year
The impact of MEM+EX and memantine on brain-derived neurotrophic factor (BDNF)
Time frame: Baseline and up to 6 months
The impact of MEM+EX and memantine on inflammatory markers
Time frame: Baseline and up to 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- University of North Carolina Lineberger Comprehensive Cancer Center Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Zev Nakamura, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Memantine and Exercise Intervention in people with Breast Cancer and Locally Advanced Breast Cancer, run by UNC Lineberger Comprehensive Cancer Center 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 9 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: looking for participants now, as of the sponsor's last update on 6 May 2026. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ashley M Hanson (+1 984-888-9244, Ashley_Hanson@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rates of recruitment (time frame: Baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 May 2026.