The purpose of this study is to assess the clinical correlates of therapeutic precision ketosis in bipolar depression and to evaluate the cardiometabolic correlates associated with therapeutic precision ketosis in bipolar depression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Participants will initiate a modified ketogenic diet under structured, intensive guidance. Simultaneously, participants will attend weekly behavioral support interviews with a psychiatrist to monitor mental health and mood stability.
Mayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGChange in depressive symptoms
Measured using the Quick Inventory for Depressive Symptomatology Clinician Rated (QIDS-C), a 16-item clinician rating, each rated on a four-point Likert scale (0-3). The total score ranges from 0 to 27. The QIDS-C is scored by summing the responses to the 16 items, with higher scores indicating more severe symptoms.
Time frame: Baseline, 6 months
Response and Remission Rates
Measured using the Montgomery-Asberg Depression Rating Scale (MADRS), with response defined as a ≥50% reduction from baseline symptoms and remission as a score \<10, providing complementary measures of symptom improvement. MADRS is a 10-item observer rating scale assessing symptoms of depression. The MADRS will be used to assess depression severity, exclude patients with suicidal ideation scoring \> 4 on question #10 and measure % of patients achieving remission defined as a MADRS \< 10.
Time frame: Baseline, 6 months
Percentage of clinically significant improvement
The proportion of participants rated as "much improved" or "very much improved" on the Clinical Global Impression for Bipolar Disorder (CGI-BP) scale. CGI-BP is a specialized tool for assessing the severity, treatment response, and efficacy of interventions in bipolar disorder. It addresses the unique features of the disorder by evaluating manic and depressive episodes separately. It consists of three components: Severity of Illness (CGI-BP-S), Global Improvement (CGI-BP-I), which tracks changes from baseline; and Efficacy Index (CGI-BP-E), which assesses treatment benefits relative to side effects.
Time frame: Baseline, 6 months
Change in anxiety symptoms
Measured using the General Anxiety Disorder 7 (GAD-7), a 7-item self-report questionnaire used to measure the severity of generalized anxiety symptoms over the past two weeks. Each item is scored on a 4-point Likert scale (0 = "Not at all" to 3 = "Nearly every day"), with a total score ranging from 0 to 21. Higher scores indicate greater anxiety severity
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Time frame: Baseline, 6 months
Prevalence rate of disordered eating
Measured using the Eating Disorder Diagnostic Scale (EDDS), a standardized measure designed to assess symptoms of eating disorders. It quantifies symptom severity and provides a diagnostic algorithm based on threshold scores that indicate probable diagnoses and subthreshold levels of disordered eating. The EDDS includes 22 items that evaluate key behaviors and cognitive symptoms associated with eating disorders.
Time frame: 6 months
Change in psychosocial functioning
Measured using the Functioning Assessment Short Test (FAST),a short, simple interview-administered instrument for patients with psychiatric disorders to assess functional recovery. The psychometric properties of this test enable it to detect differences between euthymic and acute patients with bipolar disorder. The total FAST score is the sum of each item. Lower scores indicate good functioning, while higher scores indicate increased impairment.
Time frame: Baseline, 6 months
Change in well-being
Measured using the Well-Being Index (WHO-5), a self-report instrument measuring mental well-being. It consists of five statements relating to the past two weeks. Each statement is rated on a 6-point scale, with higher scores indicating better mental well-being.
Time frame: Baseline, 6 months
Change in insulin resistance
Insulin resistance will be assessed using calculated Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) from fasting glucose and insulin levels.
Time frame: Baseline, 6 months
Change in mitochondrial function
Assessed by evaluating baseline-to-endpoint changes in mitochondrial metabolites, measured using the MMPP test developed at Mayo Clinic.
Time frame: Baseline, 6 months
Change in serum levels of high sensitivity C-reactive protein (CRP)
High sensitivity C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to systemic inflammation and is widely used as a biomarker of inflammation. These changes will be analyzed in conjunction with daily ketone body measurements, providing an index of ketosis.
Time frame: Baseline, 6 months
Change in subclinical vascular health
Assessed by changes in key vascular function and structure indicators. This includes detailed assessments of lipid profiles, focusing on biomarkers such as apolipoprotein B and advanced high-resolution lipoprotein subfraction profiling.
Time frame: Baseline, 6 months
Change in interleukin-6 IL-6
Interleukin-6 (IL-6) is a cytokine involved in immune response and inflammation. These changes will be analyzed in conjunction with daily ketone body measurements, providing an index of ketosis, and mood state assessments to explore potential correlations.
Time frame: Baseline, 6 months