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Bipolar DepressionNCT07121894

Ketogenic Intervention for Bipolar Depression

A study testing Ketogenic Diet in people with Bipolar Depression, run by Mayo Clinic at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Bipolar Depression
What is being tested?
Ketogenic Diet
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
12 Aug 2025to 1 May 2029
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Age 18-50 years
  • Willingness to change the current diet to a high fat, low carbohydrate diet
  • Diagnosis of bipolar I or II disorder, or BP schizoaffective Disorder by DSM-IV (SCID- confirmed). If a participant has already completed a structured diagnostic interview within the last 2 years or in any of the Department of Psychiatry and Psychology Mood Unit studies, existing SCID results can be used for this study; thus, they will not be required to repeat the SCID assessment. If a structured diagnostic interview was completed more than 2 years ago, the current mood state sections of the SCID must be repeated to ensure accuracy of current mood state assessment.
  • Depressive symptom severity of at least mild (MADRS > 6) with steady and stable (ie, at least 2 weeks) mood stabilization (eg, lithium, valproate, lamotrigine, carbamazepine/oxcarbamazepine, and/or atypical antipsychotic therapy) and non-psychotropic medication.
  • Urine drug screen is negative except for allowable drugs that they have been prescribed, such as benzodiazepines.
  • Pregnancy test is negative.
  • Established birth control practice for sexually active individuals.
  • Medical comorbidity is stable (hypertension, T2D, gout - uric acid in normal limits).

Who cannot join

  • No access to smartphone or internet (unless provided by sponsor)
  • Inability to provide written, voluntary, informed consent and pass (80%) comprehension assessment related to study goals, risks, and benefits.
  • Structured clinical interview confirmation of schizophrenia or presence of psychotic symptoms (both SCID and YMRS question 8>5).
  • Clinical diagnosis of personality disorder that, upon review by the study psychiatrist, of all available information (SCID, electronic health record), is the primary psychiatric diagnosis.
  • Mixed symptoms of depression defined as a YMRS ≥12 (i.e., hypomania).
  • Active suicidal ideation as defined by MADRS score >4 on question #10 or Columbia Suicide Severity Scale (C-SSRS), yes response to Question #4 (ideation, intent, but no plan) or Question #5 (ideation, intent, and plan).
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  • Any current drug and alcohol use disorder (excluding nicotine); complete (not partial) remission ≥3 months.
  • Positive toxicology screen for cannabis and cannabis use disorder by structured clinical interview. Participants who use cannabis for recreational or medicinal purposes and fail the toxicology screen can potentially be included if the Cannabis Use Disorder Identification Test (CUDIT-R) score is < 12.
  • Currently undergoing ECT, transcranial magnetic stimulation, or deep brain stimulation as an acute or maintenance treatment. Maintenance vagal nerve stimulation is allowed if the placement of device is > 1 year.
  • Current involuntary psychiatric hospitalization.
  • Already in ketosis or on a medication that causes acidosis, such as carbonic anhydrase inhibitors (e.g., acetazolamide "Diamox" and topiramate).
  • BMI < 18.5; (m) baseline LDL-c > 190.
  • Any active or unstable medical condition judged by the principal investigator as conferring significant medical risk to allow inclusion in the study, such as active severe infection.
  • Acute pancreatitis or history of lipid-associated pancreatitis.
  • Type I diabetes.
  • SGLT2 inhibitor use
  • Rare inborn errors of metabolism affecting fatty acid processing (typically diagnosed in infancy or, rarely, adolescence), such as Pyruvate carboxylase deficiency and Porphyria
  • Primary carnitine deficiency
  • Chronic renal failure, significant renal disease defined as creatinine clearance <30 or in dialysis.
  • Severe vitamin D deficiency (serum levels of 25-hydroxyvitamin D [25(OH)D] < 12 ng/mL or 30 nMol/L). Participants with abnormal vitamin D levels would be eligible if they begin supplementation and vitamin D levels are normalized before Baseline.
  • A diagnosis of osteopenia, defined as a bone mineral density (BMD) T-score between -1.0 and -2.5 on a dual-energy X-ray absorptiometry (DEXA) scan or with a history of fragility fractures
  • Clinically significant laboratory test abnormality
  • Anticipated elective surgical procedure within the next 18 weeks
  • Family history of premature coronary artery disease defined as atherosclerotic cardiovascular events (e.g., heart attack, stroke) before 55 and 65 years of age in male and female first-degree relatives, respectively.
  • History of familial hypercholesterolemia (note -current or start of statin or lipid-lowering drug as part of clinical care is not an exclusion provided managed by a primary care provider) or LDL-C>190 mg/dl (or LDL>160 mg/dl if on lipid lowering therapy) or triglycerides>500 mg/dl.
  • History of coronary disease or coronary calcifications or coronary stenosis found in invasive cardiac catheterization or imaging.
  • History of ischemic stroke or carotid plaque found on baseline common carotid intima-media thickness (IMT) ultrasound.
  • History of peripheral atherosclerotic arterial disease or any other form of clinical atherosclerosis.
  • History or current diagnosis of respiratory failure defined as a PaO₂ < 60 mmHg or SpO₂ < 90% on room air or any condition leading to clinically significant respiratory impairment
  • History or current diagnosis of liver failure or chronic liver disease with significant impairment, defined as ALT or AST > 5 times the upper limit of normal, or total bilirubin > 3 mg/dL.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Karin Lindstrom, PhD contact

507-293-3876

Lindstrom.Karin@mayo.edu

United States1 site, 1 recruiting

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

    Karin Lindstrom, PhD, 507-293-3876, Lindstrom.Karin@mayo.edu

    Kyla M Lara-Breitinger, MD

    Recruiting

Other trials in United States

About this study

Official title: Ketogenic Intervention for Bipolar Depression: An Open-Label Trial Guiding Clinical Implementation (KETO-MAYO)

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.

Being tested
Ketogenic Diet
Medical subject headings
Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ketogenic DietBehavioural

    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.

Study groups in NCT07121894
Study groupRoleWhat they receive
Ketogenic DietExperimentalPatients diagnosed with bipolar disorder and experiencing depression or depressive symptoms.
Receives: Behavioral: Ketogenic Diet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change 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.

    Measured: Baseline, 6 months

Secondary outcomes (11)

  1. 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.

    Measured: Baseline, 6 months

  2. 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.

    Measured: Baseline, 6 months

  3. 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

    Measured: Baseline, 6 months

  4. 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.

    Measured: 6 months

  5. 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.

    Measured: Baseline, 6 months

  6. 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.

    Measured: Baseline, 6 months

  7. 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.

    Measured: Baseline, 6 months

  8. Change in mitochondrial function

    Assessed by evaluating baseline-to-endpoint changes in mitochondrial metabolites, measured using the MMPP test developed at Mayo Clinic.

    Measured: Baseline, 6 months

  9. 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.

    Measured: Baseline, 6 months

  10. 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.

    Measured: Baseline, 6 months

  11. 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.

    Measured: Baseline, 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2025
  2. Study start12 Aug 2025
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion1 May 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07121894
Sponsor's protocol ID
24-013228
Status last verified
Aug 2026
First submitted
18 Jul 2025
Last updated
17 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Ketogenic Diet in people with Bipolar Depression, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Karin Lindstrom, PhD (507-293-3876, Lindstrom.Karin@mayo.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in depressive symptoms (time frame: Baseline, 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07121894.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.

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