NCT06080932

Ketogenic Intervention in Depression

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Ohio State University · Academic / Other
• Sex: All
• Age: 18 Years – 30 Years
• Healthy volunteers: Accepted

Summary

The goal of this study is to examine whether a well-formulated ketogenic diet (KD) can be implemented into a university counseling treatment program for major depression and to test whether such a program has any benefit on mental and metabolic health.

Detailed description

Major depression is a burgeoning problem that affects over five percent of adults worldwide and is rapidly increasing in the United States. From the second quarter of 2019 to June of 2020, the prevalence of symptoms of depression spiked from 6.5 to 24.3% , which was largely attributed to the COVID-19 pandemic. Major depression and suicidal ideation have increased markedly in young adults, particularly within college campuses. In 2020, counselors at the Ohio State University (OSU) experienced a surge in the number of students with various mental health issues with anxiety and depressive disorders being the most common. The escalating prevalence of depression bubbling under the surface of the ongoing COVID-19 pandemic represents a unique challenge that requires new and creative solutions. Recently, a KD was administered to adults who had been admitted to a psychiatric hospital and were suffering from various mental disorders. The dietary intervention lasted between 16 and 248 days and showed significant improvements in depression and psychotic symptoms. Ketogenic diet interventions (and ingestion of ketone esters) have also been associated with more stable brain networks, assess with functional Magnetic Resonance Imaging (fMRI). Additionally, a novel but as yet under-appreciated effect of nutritional ketosis is to induce a broad-spectrum reduction in inflammation in metabolically-impaired individuals. Elevations in a range of inflammation biomarkers has been associated with severity of depression. Although KDs have been proposed as a treatment option for mental health disorders, including schizophrenia and depression, few human clinical trials have tested the efficacy of this eating pattern specifically in a population of adults with major depression. In patients with type 2 diabetes (n=262) prescribed a KD using a novel virtual care model (Virta Health), we observed significant improvements in depressive symptoms after 10-weeks, which were directly correlated with the degree of carbohydrate restriction and nutritional ketosis as assessed by blood concentrations of ketones.

Conditions

• Depression
• Ketosis

Interventions

Type	Name	Description
OTHER	Ketogenic Diet	The diet intervention will start after all baseline testing is complete
OTHER	NIH Toolbox	IPAD-based assessments that examines cognitive function
OTHER	gradCPT	The gradCPT contains grayscale photographs of mountain scenes and city scenes. Scene images gradually transition from one image to the next
OTHER	Resting-state fMRI	Whole brain echo-planar imaging (EPI) volumes sensitive to the BOLD signal will be acquired. Images will be re-aligned, un-warped, and normalized. Confounding effects of white matter, CSF signal, and head motion will be regressed from the functional time series, followed by bandpass filtering, linear detrending and smoothing, and whole brain resting state networks will be identified (e.g., default mode network, salience network, etc).
OTHER	Task-fMRI	During whole brain EPI data acquisition, participants will be presented with words and pictures and asked to make judgements about the stimuli, such as indicating whether a particular stimulus (e.g., face-name association, word, number, or letter) has been previously presented, if a presented stimulus is a city or mountain scene, the direction an arrow is pointing (left or right), if a pair of stimuli match (e.g., faces with neutral or emotional expressions; word with a face). Behavioral responses will be recorded with an MRI compatible button box.
OTHER	CGM/CKM	Continuous Ketone/Glucose Monitor will be applied at the start of Test Day 1. The sensor will be checked by the study team at each test day and will be removed and replaced by a fresh sensor at \~2- week intervals during the study. The sensor will be removed at the end of the final test day.
BIOLOGICAL	Blood Draw	Blood samples will be collected according to the schedule in Figure 1
OTHER	Sleep Monitoring	Sleep will be assessed by ring-based acceleration with cloud technology (Oura Ring). This monitor is less burdensome than other sleep monitoring technologies and less likely to interfere with normal sleep and activity demands. Worn daily throughout intervention
BIOLOGICAL	Ketone/Glucose Monitoring	KetoMojo hand-held glucometer will be used daily to monitor dietary intervention adherence.
OTHER	Body Composition	DEXA Scanning will be done pre-, mid-, and post- intervention.
BEHAVIORAL	PHQ-9	It is a self-assessment tool used to screen and assess the severity of depression in individuals. The PHQ-9 consists of nine questions based on the nine criteria for diagnosing major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
BEHAVIORAL	WHO-5	The WHO-5, also known as the World Health Organization-Five Well-Being Index, is a self-assessment tool used to measure subjective well-being and mental health. It was developed by the World Health Organization (WHO) as a brief and reliable instrument to evaluate well-being in clinical and research settings.
BEHAVIORAL	SKID	The SKID refers to the Structured Clinical Interview for DSM Disorders (SCID). It is a widely used diagnostic tool in the field of psychiatry and clinical psychology. The SCID is a semi-structured interview designed to assess and diagnose various mental disorders according to the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM), which is published by the American Psychiatric Association.

Timeline

• Start date: 2023-02-20
• Primary completion: 2024-06-01
• Completion: 2024-12-21
• First posted: 2023-10-12
• Last updated: 2025-05-29

Locations

1 site across 1 country: United States