Evaluation of the Ketogenic Diet to Improve Post Operative Cognitive Decline in Cardiac Surgery
NCT Number: NCT06480708
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Postoperative Cognitive Dysfunction
Interventions: OTHER: Ketogenic diet|OTHER: Control diet
Sponsor: University of Missouri-Columbia
Collaborators: National Institutes of Health (NIH)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 40
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2025-05
Completion Date: 2026-10
Locations: University on Missouri Hospital, Columbia, Missouri, 65212, United States

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.

Primary Outcome Measures: Incidence of postoperative cognitive decline (POCD), POCD will be measured for 3 days postoperatively or until delirium resolves, 3 days
Secondary Outcome Measures: Neuroinflammatory metabolite concentrations in participants on ketogenic diet vs control diet, MRI/MRS scans to assess effect of ketogenic diet on neuroinflammatory markers, 10-14 days|Effect of ketogenic diet on cerebral ketosis, Measuring cerebral ketosis with MRI/MRS scans., 10-14 days|Peripheral cytokine levels in participants on ketogenic diet vs control diet, Peripheral inflammatory markers obtained through peripheral blood draw, 16 days|Effect of ketogenic diet on systemic ketosis, Peripheral ketone levels obtained through peripheral blood draw, 16 days