Ketogenic Intervention in Depression
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Ohio State University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- WHO-5 Questionnaire
Study Overview
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.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 30 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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:
- •The CCBBI screening form (https://redcap.osumc.edu/redcap/surveys/?s=N3XJ4WC7T9) will be used to assess MRI eligibility. Endorsement of items that contraindicate MRI will serve as exclusion criteria (pacemaker, stint, claustrophobia, etc.).
Arms & Interventions
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.
Intervention: Ketogenic Diet (Other)
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.
Intervention: NIH Toolbox (Other)
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.
Intervention: gradCPT (Other)
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.
Intervention: Resting-state fMRI (Other)
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.
Intervention: Task-fMRI (Other)
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.
Intervention: CGM/CKM (Other)
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.
Intervention: Blood Draw (Biological)
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.
Intervention: Sleep Monitoring (Other)
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.
Intervention: Ketone/Glucose Monitoring (Biological)
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.
Intervention: Body Composition (Other)
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.
Intervention: PHQ-9 (Behavioral)
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.
Intervention: WHO-5 (Behavioral)
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.
Intervention: SKID (Behavioral)
Outcomes
Primary Outcomes
WHO-5 Questionnaire
Time Frame: Up to ~ 12 weeks
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
The Hamilton Depression Scale
Time Frame: Up to ~ 12 Weeks
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.
Finger Stick Glucose
Time Frame: Up to ~ 12 Weeks
changes in fasting glucose levels.
Finger Stick BHB
Time Frame: Up to ~ 12 Weeks
changes in fasting ketone levels.
Secondary Outcomes
- Blood Pressure(Up to ~ 12 Weeks)
- Changes in total body weight ( kg)(Up to ~ 12 Weeks)
- Task-fMRI(Up to ~ 12 Weeks)
- Changes in BMI(Up to ~ 12 Weeks)
- PHQ-9(Up to ~ 12 Weeks)
- CGM/CKM(Up to ~ 12 Weeks)
- Metabolic Panel(Up to ~ 12 Weeks)
- Resting State fMRI(Up to ~ 12 Weeks)
- Lean Body Mass (kg)(Up to ~ 12 Weeks)
- Cognitive Testing(Up to ~ 12 Weeks)