Ketogenic Intervention for Bipolar Depression
Ketogenic Intervention for Bipolar Depression: An Open-Label Trial Guiding Clinical Implementation (KETO-MAYO)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 50 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study looks at how a high-fat, low-carbohydrate diet affects depression and heart and metabolic health. The diet aims to cause ketosis, when the body uses fat for fuel. It is for adults ages 18–50 with bipolar depression or bipolar-type schizoaffective disorder.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- You are 18–50 years old.
- You are willing to switch to a high-fat, low-carbohydrate diet.
- A study interview confirms bipolar I, bipolar II, or bipolar-type schizoaffective disorder. Some past interviews may count.
- You have at least mild depression, and your mood-stabilizing and other medicines have been stable for at least 2 weeks.
- Your urine drug test is negative, except for allowed prescribed drugs.
- Your pregnancy test is negative.
- You use an established birth control method if you are sexually active.
- Other health conditions, such as high blood pressure, type 2 diabetes, or gout, are stable.
Who can't join
- You lack smartphone or internet access unless the sponsor provides it, cannot freely give written consent, or score below 80% on the study understanding test.
- You have schizophrenia, symptoms such as seeing or hearing things that are not there, a personality disorder as your main diagnosis, unusually high energy with depression, or active suicidal thoughts.
- You have a current drug or alcohol use disorder other than nicotine use. Full recovery must last at least 3 months. Some cannabis use may be allowed after testing.
- You are hospitalized for mental health care against your will, or receive ECT, magnetic brain stimulation, or deep brain stimulation. Ongoing vagus nerve stimulation may be allowed if the device was placed over a year ago.
- You already have ketosis, take medicines that cause acid buildup or SGLT2 diabetes medicines, have type 1 diabetes, or have certain rare conditions affecting how your body uses fat.
- You have serious or unstable illness, certain pancreas problems, severe kidney, liver, or breathing problems, major abnormal lab results, or planned non-emergency surgery within 18 weeks.
- You are underweight, have low bone density or fractures from minor injuries, or have severe vitamin D deficiency. Vitamin D deficiency may be treated before the study starts.
- You have very high cholesterol or blood fats, inherited high cholesterol, artery disease, a past stroke caused by blocked blood flow, or a close family history of early heart or artery disease.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria * 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). Exclusion Criteria: * 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). * 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.
Study sites (1)
MN
- Mayo Clinic in Rochester · Rochester, MN 55905Karin Lindstrom, PhD · Study contact · 507-293-3876 · Lindstrom.Karin@mayo.eduKyla M Lara-Breitinger, MD · Principal investigatorMark Frye, MD · Principal investigatorMore trials in Rochester