Oxaloacetate for Cognitive Function in Breast Cancer Survivors

Overseen By Barbara Kahn-Mills

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Sleep medications, Anxiety medications, Narcotics, Cannabis

Disqualifiers: Chronic illness, Psychiatric condition, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if oxaloacetate, a natural substance in the body, can reduce memory and thinking problems in women who have survived early-stage breast cancer (stages 0 to IIIA). These cognitive issues often occur after cancer treatments, and oxaloacetate might help by reducing brain inflammation. Women who completed their main cancer treatments at least a year ago and still experience significant memory or thinking problems may be suitable for this trial. Participants will take oxaloacetate pills twice a day for eight weeks. As a Phase 2 trial, this research measures how well oxaloacetate works in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take medications that interfere with cognitive functioning, like those for sleep, anxiety, or pain. You can continue endocrine or HER-2 targeted therapy if you are on them.

Is there any evidence suggesting that oxaloacetate is likely to be safe for humans?

Research has shown that anhydrous enol-oxaloacetate is safe and easy to handle. One study found that taking 1000–3000 mg daily was safe and manageable for participants. In another study, people did not report any serious side effects at similar doses. These findings suggest that the treatment is generally safe for short-term use in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for cognitive issues in breast cancer survivors, which might focus on symptom management or rehabilitation, anhydrous enol-oxaloacetate is unique because it leverages a new active ingredient that targets cellular energy production. This approach aims to enhance cognitive function by potentially boosting the brain's energy levels, which could lead to clearer thinking and better memory. Researchers are excited about this treatment because it offers a novel mechanism of action that could provide relief more directly and efficiently than current options.

What evidence suggests that oxaloacetate might be an effective treatment for cognitive complaints in breast cancer survivors?

Research has shown that oxaloacetate may improve thinking and memory in individuals experiencing brain fog. One study found that 40.5% of patients with conditions like chronic fatigue syndrome and long COVID experienced better cognitive function after using oxaloacetate. This trial will evaluate the effects of anhydrous enol-oxaloacetate on cognitive function in breast cancer survivors. Researchers hypothesize that it might help with similar cognitive issues, possibly by reducing brain inflammation. Other studies have found oxaloacetate to be safe, although improvements in blood levels and cognitive scores were not always consistent. Overall, early findings are promising for its potential to help with cognitive problems by addressing inflammation. ^{2 6 7 8 9}

Who Is on the Research Team?

Patricia A. Ganz

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for women who've had early-stage breast cancer (stage 0-IIIa), are 12+ months post-treatment but within 5 years of diagnosis, and have cognitive complaints. They must be able to complete surveys in English, sign consent, use contraception if necessary, and not have active cancer or serious illnesses.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I was diagnosed with early stage breast cancer, finished initial treatments over a year ago, but it's been less than 5 years since my diagnosis.

Ability to complete evaluation surveys in English

Exclusion Criteria

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

I have a serious health or mental condition that could affect my participation in the study.

Participants may not be receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anhydrous enol-oxaloacetate orally twice daily for 8 weeks

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anhydrous Enol-oxaloacetate

Trial Overview The study tests oxaloacetate's effectiveness in reducing cognitive issues after breast cancer treatment. Participants will take this natural supplement over an 8-10 week period and answer questionnaires to assess changes in their cognitive function.

How Is the Trial Designed?

Group I: Supportive care (anhydrous enol-oxaloacetate) Experimental Treatment 2 Interventions

Patients receive anhydrous enol-oxaloacetate PO BID for 8 weeks in the absence of worsening symptoms or unacceptable toxicity.

Anhydrous Enol-oxaloacetate is already approved in United States for the following indications:

Approved in United States as Anhydrous Enol-oxaloacetate for:

• None approved; Investigational for glioblastoma multiforme, amyotrophic lateral sclerosis, Alzheimer's disease, and cognitive complaints in breast cancer survivors

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

MetVital, Inc.

Industry Sponsor

Trials

2

Recruited

100+

Breast Cancer Research Foundation

Collaborator

Trials

79

Recruited

40,500+

Published Research Related to This Trial

Women who underwent adjuvant CMF chemotherapy for breast cancer showed significantly worse cognitive performance over 20 years later compared to women without a cancer diagnosis, particularly in areas like memory, processing speed, and executive functioning.

Despite experiencing fewer symptoms of depression, these survivors reported more memory complaints, indicating that cognitive deficits from chemotherapy can persist long after treatment has ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. Koppelmans, V., Breteler, MM., Boogerd, W., et al.[2013]

Approximately one-third of breast cancer survivors who underwent adjuvant chemohormonal therapy reported long-term cognitive impairments, affecting memory, attention, and language skills.

The article highlights the need for further research, including prospective longitudinal studies, to better understand the neuropsychological effects of these therapies and their impact on survivors' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive function after systemic therapy for breast cancer. Olin, JJ.[2005]

The combined exercise and game-based cognitive training intervention for breast cancer survivors led to a significant increase in insulin-like growth factor 1 (IGF-1) levels, which may be linked to improvements in cognitive function, as indicated by neurocognitive test performance.

The study highlights the feasibility of using fingerstick bloodspot samples for biomarker research, making it easier to conduct studies in various settings, including during pandemic restrictions, while minimizing participant discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Exercise and Game-Based Cognitive Training Intervention: Correlative Pilot Study of Neurotrophic and Inflammatory Biomarkers for Women With Breast Cancer. Myers, J., Pathak, HB., He, J., et al.[2023]

Breast cancer survivors often experience cognitive deficits after chemotherapy and hormonal therapy, which can significantly impact their quality of life, despite neuropsychological tests showing normal performance levels.

Imaging studies indicate that these cognitive issues may be linked to anatomical changes in the brain and altered neural activation patterns, suggesting a need for targeted interventions like cognitive remediation therapy and healthy lifestyle prescriptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Deficits in Breast Cancer Survivors After Chemotherapy and Hormonal Therapy. Frank, JS., Vance, DE., Triebel, KL., et al.[2015]

A 24-week aerobic exercise program for postmenopausal breast cancer survivors showed a significant improvement in processing speed, with participants completing a cognitive test 14.2 seconds faster compared to those who maintained their usual lifestyle.

While self-reported cognitive function did not show significant improvement, brain imaging revealed functional changes in several regions, suggesting that aerobic exercise may positively influence cognitive processing in cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT. Campbell, KL., Kam, JWY., Neil-Sztramko, SE., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04290897

Study Details | NCT04290897 | Oxaloacetate for the ... This phase II trial studies how well oxaloacetate works in reducing cognitive complaints in stage 0-IIIA breast cancer survivors. Oxaloacetate is a natural ...

2. withpower.com withpower.com/trial/phase-3-breast-carcinoma-in-situ-10-2021-f3c6e

Oxaloacetate for Cognitive Function in Breast Cancer ... This phase II trial studies how well oxaloacetate works in reducing cognitive complaints in stage 0-IIIA breast cancer survivors. Oxaloacetate is a natural ...

3. mecfs-research.org mecfs-research.org/wp-content/uploads/2025/06/Alan-Cash_International-MECFS-Conference-2025_Anhydrous-Enol-Oxaloacetate-Treatment-of-MECFS.pdf

Oxaloacetate CFS Oxaloacetate significantly improves effective Cognitive Function in. ME/CFS and Long COVID Patients, decreasing Brain Fog. • 40.5% of the Oxaloacetate group ...

4. metvital.com metvital.com/metvital-inc-announces-fda-fast-track-designation-of-anhydrous-enol-oxaloacetate-aeo-for-the-treatment-of-patients-with-newly-diagnosed-glioblastoma-multiforme/

MetVital, Inc. Announces FDA Fast Track Designation of ... Anhydrous Enol-Oxaloacetate is a molecule that has demonstrated safety and efficacy in animal models with human glioblastoma tissue implants, in animal models ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8084114/

Safety and target engagement profile of two oxaloacetate ... We did not demonstrate consistent blood level changes and cognitive scores did not improve. CONCLUSIONS: 1000 mg OAA, taken twice daily for 1 month, is safe in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04290897

Study Details | NCT04290897 | Oxaloacetate for the ... A Phase II Single Arm Trial Evaluating the Safety and Efficacy of Anhydrous Enol-Oxaloacetate on Improving Cognitive Complaints in Breast Cancer Survivors.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9238249/

Oxaloacetate Treatment For Mental And Physical Fatigue ... 1000–3000 mg anhydrous enol-oxaloacetate daily was both safe and tolerable in this population for the duration of the trial.

8. synapse.patsnap.com synapse.patsnap.com/drug/5b35a4427aaf45b0a2b2b9dcbba0a2ef

Anhydrous Enol-Oxaloacetate - Drug Targets, Indications, ... A Phase II Single Arm Trial Evaluating the Safety and Efficacy of Anhydrous Enol-Oxaloacetate on Improving Cognitive Complaints in Breast Cancer Survivors.

9. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1483876/full

RESTORE ME: a RCT of oxaloacetate for improving fatigue ... Results: Anhydrous enol-oxaloacetate (oxaloacetate) was well tolerated at the tested doses. Oxaloacetate significantly reduced fatigue by more ...