Ketogenic Diet for Cognitive Impairment After Surgery

Overseen By Paige A Spencer, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Missouri-Columbia

Must not be taking: GLP-1 agonists

Disqualifiers: Dementia, Alzheimer's, Parkinson's, others

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

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Postoperative cognitive decline (POCD) is a significant neurological problem that commonly follows coronary artery bypass grafting surgery (CABG) in elderly patients. This can result in longer hospital stays and generate worsening morbidity and mortality. Furthermore, POCD often persists in some patients for more than a year and puts them at higher risk for developing Alzheimer's Disease or dementia. The cause of POCD is a topic of ongoing work, with recent hypotheses linked with cell dysfunction and death in the brain, and neuroinflammation related to the surgical trauma and related systemic inflammation. In this project, the investigators will test whether the pre-operative use (14 days) of a ketogenic diet (KD), compared to a control diet (CD) will lower the incidence, duration, and severity of POCD in cardiac patients. The ketogenic diet has been associated with improved memory function, as well as reduction of inflammation in conditions such as epilepsy, Alzheimer's Disease and Parkinson's Disease. A subset of patients from each group will also undergo a 7 Tesla magnetic resonance imaging and spectroscopy scan, where key brain metabolites of mitochondrial function and neuronal integrity will be measured in the prefrontal cortex and hippocampus. In the KD group, cerebral b-hydroxybutyrate (BHB) to evaluate cerebral ketosis will also be measured. These will be measured prior to starting the KD/CD and after a minimum of 10 days on the KD/CD. From both CD and KD groups, levels of key cytokines linked with inflammation will be measured during the protocol. Our outcome parameters for POCD will include measures that evaluate cognition, delirium and length of hospitalization. The following hypotheses will be investigated: 1) lower incidence, duration and severity of POCD in the KD group, compared to the CD group; and 2) better pre-operative values of neuronal integrity and in the KD group, higher levels of brain ketone levels will be associated with patients who do not experience POCD or have less severe POCD. This project tests the use of the multi-factorial effects of the KD for an important problem in Anesthesiology. With state-of-the-art imaging technology and cytokine evaluation, the investigators hypothesize this work can have substantial implications for prevention and management of postoperative cognitive decline.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using GLP-1 agonists, you cannot participate in the trial.

What evidence supports the effectiveness of the ketogenic diet as a treatment for cognitive impairment after surgery?

Research shows that a ketogenic diet, which is high in fats and low in carbohydrates, can improve memory in older adults with mild cognitive impairment. Additionally, it has shown promise in improving cognition in dementia and other neurological conditions, suggesting potential benefits for cognitive impairment after surgery. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

The ketogenic diet is generally safe for humans, but some people may experience side effects like high cholesterol (dyslipidemia), constipation, and fatigue. In a study of older adults, 15% reported such adverse events. ^{3 6 7 8 9}

How does the ketogenic diet treatment for cognitive impairment after surgery differ from other treatments?

The ketogenic diet is unique because it shifts the body's energy source from glucose to fats, increasing ketone levels in the blood, which may protect brain function and improve cognitive abilities. Unlike other treatments, it provides an alternative energy source to the brain and has shown potential benefits in conditions like traumatic brain injury and Alzheimer's disease. ^{9 10 11 12 13}

Research Team

Antoinette Burger, PhD

Principal Investigator

Department of Anesthesiology and Perioperative Medicine, University of Missouri-Columbia

Eligibility Criteria

This trial is for elderly patients undergoing coronary artery bypass grafting surgery who may be at risk of postoperative cognitive decline (POCD). Participants must be willing to follow a special diet before their surgery. Details on specific inclusion and exclusion criteria are not provided.

Inclusion Criteria

Negative for delirium on the CAM at baseline

I am 60 years old or older.

I am scheduled for heart bypass surgery that may include valve repair or replacement.

Exclusion Criteria

I have been diagnosed with dementia, Alzheimer's, or Parkinson's.

I need or have had urgent coronary artery bypass graft surgery, with or without valve surgery.

I am in the hospital for bypass or valve surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Diet Intervention

Participants follow either a ketogenic diet or control diet for 14 days prior to surgery

2 weeks

Dietary monitoring and compliance checks

Surgery and Immediate Postoperative Monitoring

Participants undergo open heart surgery and are monitored for postoperative cognitive decline

3 days

In-hospital monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments and imaging

2 weeks

Follow-up visits for cognitive assessments and imaging

Treatment Details

Interventions

• Ketogenic Diet

Trial Overview The study compares the effects of a ketogenic diet (KD) versus a control diet (CD) on POCD in cardiac patients. It involves pre-operative use of these diets for 14 days and includes advanced brain imaging and inflammation marker tests.

Participant Groups

Group I: Ketogenic diet group Experimental Treatment 1 Intervention

20 participants will be randomized to a ketogenic diet group and will consume the ketogenic diet for 14 days prior to undergoing open heart surgery.

Group II: Control diet group Active Control 1 Intervention

20 participants will be randomized to a control diet group and will consume the control diet for 14 days prior to undergoing open heart surgery.

Who Is Running the Clinical Trial?

University of Missouri-Columbia

Lead Sponsor

Trials

387

Recruited

629,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

A new ketogenic diet (KD) designed for adults significantly improved recovery from traumatic brain injury (TBI) in mice, showing reduced sensorimotor deficits and improved spatial memory over a 70-day study period.

The new-KD increased levels of Beta-hydroxybutyrate (β-HB) and enhanced the mTOR pathway, leading to reduced inflammation and tissue damage, suggesting it has therapeutic potential for treating TBI in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice. Thau-Zuchman, O., Svendsen, L., Dyall, SC., et al.[2021]

In a study of 200 older patients (median age 70) on a ketogenic diet, 67% reported beneficial outcomes, including significant weight loss for 79% of those seeking it, improved glucose control for 54% of those with diabetes, and positive effects on cancer outcomes for 63% of patients pursuing that goal.

While the ketogenic diet showed promise for various health issues in older adults, 15% of participants experienced adverse events, including dyslipidemia and constipation, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients. Almodallal, Y., Cook, K., Lammert, LM., et al.[2023]

In a mouse model of malignant glioma, a ketogenic diet (KetoCal®) significantly increased survival by approximately 5 days compared to a standard diet, indicating its potential as a supportive treatment in cancer therapy.

The combination of the ketogenic diet and radiation therapy showed more than additive effects, with tumor growth significantly reduced in most mice on the ketogenic diet, suggesting that metabolic changes from the diet could enhance the effectiveness of conventional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. Abdelwahab, MG., Fenton, KE., Preul, MC., et al.[2022]

A clinical decision support alert significantly reduced the prescription of carbohydrate-containing medications in hospitalized children on a ketogenic diet, decreasing orders from 0.69 to 0.35 per patient-day, which prevented 256 inappropriate orders.

The alert was accepted 57% of the time when it fired, demonstrating that user-centered design can effectively influence prescriber behavior and enhance patient safety without overwhelming healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reducing Prescribing Errors in Hospitalized Children on the Ketogenic Diet. Siegel, BI., Johnson, M., Dawson, TE., et al.[2021]

A 4-year-old girl with a rare FBXL4 gene mutation and severe lactic acidosis was successfully treated with a ketogenic diet (KD) after standard treatments failed, highlighting the KD's potential in managing mitochondrial disorders.

This case represents the first documented use of parenteral KD to effectively reduce lactic acidosis in a patient with mitochondrial depletion syndrome, suggesting a promising nonpharmacological intervention for similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. İnci, A., Aktaş, E., Cengiz Ergin, FB., et al.[2022]

References

1. Australia pubmed.ncbi.nlm.nih.gov

A new ketogenic formulation improves functional outcome and reduces tissue loss following traumatic brain injury in adult mice. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Dietary ketosis enhances memory in mild cognitive impairment. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Ketogenic Diet for the Treatment and Prevention of Dementia: A Review. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Reducing Prescribing Errors in Hospitalized Children on the Ketogenic Diet. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Core outcome set development for childhood epilepsy treated with ketogenic diet therapy: Results of a scoping review and parent interviews. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Ketogenic Diet as a potential treatment for traumatic brain injury in mice. [2022]

11. Ireland pubmed.ncbi.nlm.nih.gov

Effects of a medium-chain triglyceride-based ketogenic formula on cognitive function in patients with mild-to-moderate Alzheimer's disease. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

Effects of unbalanced diets on cerebral glucose metabolism in the adult rat. [2019]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Ketogenic diet does not impair spatial ability controlled by the hippocampus in male rats. [2018]