Ketogenic Intervention in Depression

NCT ID: NCT06080932

Last Updated: 2025-05-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-20

Study Completion Date

2024-12-21

Brief Summary

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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

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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

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Depression Ketosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Ketogenic Diet

The KD will follow general principles as we have described with the aim to achieve blood ketones \>0.5 mM, which will require most participants to consume \<50 g/day carbohydrate and \~1.5 g/kg reference weight protein. Fat will comprise the remaining calories with an emphasis on monounsaturated and saturated sources from whole foods.

Group Type EXPERIMENTAL

Ketogenic Diet

Intervention Type OTHER

The diet intervention will start after all baseline testing is complete

NIH Toolbox

Intervention Type OTHER

IPAD-based assessments that examines cognitive function

gradCPT

Intervention Type OTHER

The gradCPT contains grayscale photographs of mountain scenes and city scenes. Scene images gradually transition from one image to the next

Resting-state fMRI

Intervention Type OTHER

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).

Task-fMRI

Intervention Type OTHER

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.

CGM/CKM

Intervention Type OTHER

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.

Blood Draw

Intervention Type BIOLOGICAL

Blood samples will be collected according to the schedule in Figure 1

Sleep Monitoring

Intervention Type OTHER

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

Ketone/Glucose Monitoring

Intervention Type BIOLOGICAL

KetoMojo hand-held glucometer will be used daily to monitor dietary intervention adherence.

Body Composition

Intervention Type OTHER

DEXA Scanning will be done pre-, mid-, and post- intervention.

PHQ-9

Intervention Type BEHAVIORAL

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).

WHO-5

Intervention Type BEHAVIORAL

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.

SKID

Intervention Type BEHAVIORAL

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.

Interventions

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Ketogenic Diet

The diet intervention will start after all baseline testing is complete

Intervention Type OTHER

NIH Toolbox

IPAD-based assessments that examines cognitive function

Intervention Type OTHER

gradCPT

The gradCPT contains grayscale photographs of mountain scenes and city scenes. Scene images gradually transition from one image to the next

Intervention Type 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).

Intervention Type 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.

Intervention Type 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.

Intervention Type OTHER

Blood Draw

Blood samples will be collected according to the schedule in Figure 1

Intervention Type BIOLOGICAL

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

Intervention Type OTHER

Ketone/Glucose Monitoring

KetoMojo hand-held glucometer will be used daily to monitor dietary intervention adherence.

Intervention Type BIOLOGICAL

Body Composition

DEXA Scanning will be done pre-, mid-, and post- intervention.

Intervention Type OTHER

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).

Intervention Type 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.

Intervention Type 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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* OSU students (age 18-30 years at the time of enrollment) with confirmed major depressive disorder as determined by SCID-5 diagnosis at baseline testing.
* Currently engaged in counseling treatment for depression at CCS
* Available for a 12-week period and indicate willingness and ability to eat KD foods as prescribed

Exclusion Criteria

* Disordered eating, as evidenced by meeting criteria for Anorexia Nervosa, Bulimia Nervosa, Binge Eating Disorder, Other Specified Eating Disorder, Unspecified Eating Disorder, or Avoidant Restrictive Eating Disorder during the SCID-5 interview at baseline testing.
* Substantial imminent risk of suicide as assessed during the SCID-5 interview.
* Body mass index (BMI) \< 20 kg/m2
* Habitual consumption of a structured low-carbohydrate diet in the last 6-months
* Gastrointestinal disorders or allergies that would prevent adherence to prescribed diets
* Alcohol consumption in excess of 3 drinks/daily or 14 drinks/weekly
* Diagnosed diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or use of diabetic medications other than metformin
* Inability to access or prepare appropriate KD foods/meals
* Pregnant, lactating, or planning on becoming pregnant during the study
* Unwilling to perform finger-stick blood testing or continuous glucose/ketone monitoring

Exclusion for optional MRI:
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Ohio State University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The Ohio State University

Columbus, Ohio, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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2022H0271

Identifier Type: -

Identifier Source: org_study_id

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