NCT06480708

Brief Summary

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
12mo left

Started Jan 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress24%
Jan 2026May 2027

First Submitted

Initial submission to the registry

June 15, 2024

Completed
13 days until next milestone

First Posted

Study publicly available on registry

June 28, 2024

Completed
1.6 years until next milestone

Study Start

First participant enrolled

January 15, 2026

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2026

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2027

Last Updated

June 11, 2025

Status Verified

June 1, 2025

Enrollment Period

11 months

First QC Date

June 15, 2024

Last Update Submit

June 6, 2025

Conditions

Keywords

Postoperative Cognitive DeclineKetogenic dietKetosisNeuroinflammationCell apoptosis7T MRIProton magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (1)

  • Incidence of postoperative cognitive decline (POCD)

    POCD will be measured for 3 days postoperatively or until delirium resolves

    3 days

Secondary Outcomes (4)

  • Neuroinflammatory metabolite concentrations in participants on ketogenic diet vs control diet

    10-14 days

  • Effect of ketogenic diet on cerebral ketosis

    10-14 days

  • Peripheral cytokine levels in participants on ketogenic diet vs control diet

    16 days

  • Effect of ketogenic diet on systemic ketosis

    16 days

Study Arms (2)

Ketogenic diet group

EXPERIMENTAL

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.

Other: Ketogenic diet

Control diet group

ACTIVE COMPARATOR

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.

Other: Control diet

Interventions

The ketogenic diet consisting of fats (70%), protein (20%) and carbohydrates (10%) will be consumed for 14 days prior to undergoing open-heart surgery, and up to 6 days postoperatively or until discharge (if within 6 days postoperatively).

Ketogenic diet group

The control diet consisting of a Mediterranean diet, at 25% fat, 20% protein and 55% carbohydrates will be consumed for 14 days prior to undergoing open-heart surgery, and up to 6 days postoperatively or until discharge (if within 6 days postoperatively).

Control diet group

Eligibility Criteria

Age60 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 60 years old
  • Undergoing elective on-pump coronary artery bypass grafting (CABG) surgery with/without valve repair/replacement.
  • Mini-Cog score \>4 at baseline.
  • Negative for delirium on the CAM at baseline.

You may not qualify if:

  • Pre-existing diagnosis of dementia, Alzheimer's Disease, Parkinson's Disease.
  • Emergent CABG ± valve surgery.
  • Patients already hospitalized for CABG ± valve surgery.
  • Patients using GLP-1 agonists.
  • Inability to provide written, informed consent in English.
  • Patients who cannot tolerate the KD.
  • Patients with alcoholism.
  • Patients with liver failure.
  • Patients with uremia.
  • Mini-Cog score \<4 at baseline.
  • Positive for delirium on the CAM at baseline.
  • Claustrophobia
  • Patients with any metal in their body.
  • Patients with pacemakers/internal defibrillators/neurostimulators.
  • Patients who have any form of stents.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University on Missouri Hospital

Columbia, Missouri, 65212, United States

Location

MeSH Terms

Conditions

Postoperative Cognitive ComplicationsKetosisNeuroinflammatory Diseases

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Postoperative ComplicationsPathologic ProcessesPathological Conditions, Signs and SymptomsCognitive DysfunctionCognition DisordersNeurocognitive DisordersMental DisordersAcidosisAcid-Base ImbalanceMetabolic DiseasesNutritional and Metabolic DiseasesNervous System DiseasesInflammation

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-RestrictedDiet TherapyNutrition TherapyTherapeuticsDietNutritional Physiological PhenomenaDiet, Food, and NutritionPhysiological Phenomena

Study Officials

  • Antoinette Burger, PhD

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

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Antoinette Burger, PhD

CONTACT

Paige A Spencer, BA

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

June 15, 2024

First Posted

June 28, 2024

Study Start

January 15, 2026

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

May 1, 2027

Last Updated

June 11, 2025

Record last verified: 2025-06

Data Sharing

IPD Sharing
Will not share

We will conform to institutional (University of Missouri) and NIH data and resource sharing policies. New methods, data, and insights that arise from the work conducted will be available to benefit the scientific community and the public according to these guidelines, which include: i) timely publication of results from project findings; ii) presentation of results at local/national/ international meetings/symposia; iii) deposition of certain large data-sets into public repositories; iv) project compliance with any Freedom of Information Act requests. Should any intellectual property arise which requires a patent, the investigators will ensure that the technology (materials and data) remains widely available to the research community in accordance with University policies and the NIH Principles and Guidelines document.

Locations