Ketogenic Intervention in Depression

NCT06080932 | Completed DMC

• 1 other identifier: 2022H0271
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Depression; Ketosis

Outcome Measures

Primary Outcomes (4)

• WHO-5 Questionnaire

  The WHO-5 (World Health Organization-Five Well-Being Index) is a self-assessment questionnaire used to measure subjective well-being and mental health. It was developed by the World Health Organization (WHO) and consists of five statements related to positive mood, vitality, and general interest in life. The five statements in the WHO-5 questionnaire are as follows: I have felt cheerful and in good spirits. I have felt calm and relaxed. I have felt active and vigorous. I woke up feeling fresh and rested. My daily life has been filled with things that interest me. Respondents are asked to rate each statement based on how they have felt over the past two weeks, using a six-point Likert scale ranging from "at no time" to "all of the time." The scores for each item are summed, resulting in a total score ranging from 0 to 25. Higher scores indicate better well-being

  Up to ~ 12 weeks

• The Hamilton Depression Scale

  Hamilton Depression Scale consists of 17 items that cover various symptoms of depression, including depressed mood, guilt, suicidal thoughts, insomnia, agitation, weight loss, and somatic symptoms. Each item is rated on a scale from 0 to 4 or 0 to 2, depending on the item, with higher scores indicating more severe symptoms. The scale is typically administered by a trained healthcare professional who interviews the individual and rates their symptoms based on their observations and the individual's self-report. The rater assesses the severity of each symptom and determines the appropriate score for each item. The total score on the Hamilton Depression Scale can range from 0 to 52, with higher scores indicating greater severity of depression. However, it is important to note that the interpretation of the total score requires clinical judgment and consideration of the individual's overall presentation and context.

  Up to ~ 12 Weeks

• Finger Stick BHB

  changes in fasting ketone levels.

  Up to ~ 12 Weeks

• Finger Stick Glucose

  changes in fasting glucose levels.

  Up to ~ 12 Weeks

Secondary Outcomes (10)

• PHQ-9

  Up to ~ 12 Weeks

• CGM/CKM

  Up to ~ 12 Weeks

• Metabolic Panel

  Up to ~ 12 Weeks

• Blood Pressure

  Up to ~ 12 Weeks

• Cognitive Testing

  Up to ~ 12 Weeks

Study Arms (1)

Ketogenic Diet

EXPERIMENTAL

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.

Other: Ketogenic Diet; Other: NIH Toolbox; Other: gradCPT; Other: Resting-state fMRI; Other: Task-fMRI; Other: CGM/CKM; Biological: Blood Draw; Other: Sleep Monitoring; Biological: Ketone/Glucose Monitoring; Other: Body Composition; Behavioral: PHQ-9; Behavioral: WHO-5; Behavioral: SKID

Interventions

Ketogenic Diet OTHER

The diet intervention will start after all baseline testing is complete

Ketogenic Diet

NIH Toolbox OTHER

IPAD-based assessments that examines cognitive function

Ketogenic Diet

gradCPT OTHER

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

Ketogenic Diet

Resting-state fMRI 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).

Ketogenic Diet

Task-fMRI 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.

Ketogenic Diet

CGM/CKM 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.

Ketogenic Diet

Blood Draw BIOLOGICAL

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

Ketogenic Diet

Sleep Monitoring 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

Ketogenic Diet

Ketone/Glucose Monitoring BIOLOGICAL

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

Ketogenic Diet

Body Composition OTHER

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

Ketogenic Diet

PHQ-9 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).

Ketogenic Diet

WHO-5 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.

Ketogenic Diet

SKID 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.

Ketogenic Diet

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Depression; Ketosis

Interventions

Diet, Ketogenic; Blood Specimen Collection; Ketones; Body Composition; Patient Health Questionnaire

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Organic Chemicals; Biochemical Phenomena; Chemical Phenomena; Metabolism; Body Constitution; Surveys and Questionnaires; Data Collection; Epidemiologic Methods; Psychological Tests; Behavioral Disciplines and Activities; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2023
• First Posted: October 12, 2023
• Study Start: February 20, 2023
• Primary Completion: June 1, 2024
• Study Completion: December 21, 2024
• Last Updated: May 29, 2025

Record last verified: 2025-05

Locations

US (1)