Brain Small Chain Fatty Acid Metabolism in Bipolar Disorder: Ketones

NCT ID: NCT06335875

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-07
• Study Completion Date: 2025-09-03

Brief Summary

Small exploratory open-label pilot study to assess supplementation of a ketone ester (Juvenescence) combined with a 'ketogenic-mimicking diet' as a potential therapy for persons with bipolar disorder.

Detailed Description

The overarching goal of this open-label, exploratory pilot study is to explore biomechanistic effects of exogenous ketone supplementation combined with a low glycemic diet (in effect, a 'ketogenic-mimicking diet') for patients with bipolar disorder. This represents a less restrictive metabolic intervention compared to a strict ketogenic diet while replicating two foundational elements of the ketogenic diet: low levels of glycemic/insulin signaling and high levels of circulating ketones. In addition to assessments of mood stability and global functioning, functional neuroimaging data will be obtained to better characterize the biomechanistic effects of this intervention.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bipolar Disorder

Participants will follow an intervention consisting of dietary changes and ketone ester supplementation for 90 +/- 10 days. The dietary changes are intended to reduce glycemic spiking and include: not consuming sweets, not consuming soda, replacing 'white' grains with whole grain alternatives, and reserving any fruit consumption for the end of meals. During the same time period, participants will consume the ketone ester supplement, consisting of 19 g Juvenescence Cognitive Switch™ (=12.5 g active C8-KE) diluted in water twice per day.

Group Type: EXPERIMENTAL

Ketone Ester Beverage

Intervention Type: DIETARY_SUPPLEMENT

Participants will consume ketone ester (KE) beverage, consisting of 19 g (=12.5 g active C8-KE) of Juvenescence Cognitive Switch™ diluted in water, twice per day

Low Glycemic Index Diet

Intervention Type: BEHAVIORAL

Participants will practice four dietary changes: 1. Not consuming sweets/candy, 2. Not consuming soda, 3. Replacing 'white' grains with complex carbohydrates such as brown rice or quinoa, and 4. Reserving any fruit consumption for the end of meals.

Interventions

Ketone Ester Beverage

Participants will consume ketone ester (KE) beverage, consisting of 19 g (=12.5 g active C8-KE) of Juvenescence Cognitive Switch™ diluted in water, twice per day

Intervention Type: DIETARY_SUPPLEMENT

Low Glycemic Index Diet

Participants will practice four dietary changes: 1. Not consuming sweets/candy, 2. Not consuming soda, 3. Replacing 'white' grains with complex carbohydrates such as brown rice or quinoa, and 4. Reserving any fruit consumption for the end of meals.

Intervention Type: BEHAVIORAL

Other Intervention Names

Juvenescence Cognitive Switch™; Ketogenic-mimicking Diet

Eligibility Criteria

Inclusion Criteria

• 18 and older
• Able to provide informed consent
• Diagnosis of bipolar disorder, type I or II as determined primarily via medical/psychiatric documentation provided from mental health provider with patient consent
• Regular access to smart phone capable of syncing biometric wearable data collection
• If taking psychiatric medications, on stable regimen as defined by no medication changes for mood stabilizers and/or antipsychotics in prior 4 weeks

Exclusion Criteria

• Inability to adhere to dietary changes as specified in protocol (e.g., not in control of food selection)
• History of moderate-to-severe traumatic brain injury, e.g. loss of consciousness > 10 min, neurologic sequela
• Evidence of large vessel stroke or mass lesion on previous MRI or MRI obtained during study
• History of significant GI disease (e.g., malabsorptive disorder, gastric cancer, intestinal resection)
• Pregnancy (as determined via urine pregnancy test at study initiation), if capable of becoming pregnant, or breastfeeding
• Unwilling to utilize birth control method during course of study (e.g., barrier contraception, oral contraceptive, IUD), if capable of becoming pregnant
• Currently receiving treatment with insulin (e.g., chronic pancreatitis, diabetes mellitus)
• History of mitochondrial disorder and/or significant uncontrolled metabolic/medical disorder
• Active/current illicit substance use (and/or consumption of >1 alcoholic beverages per day) - defined as using psychoactive medications not as prescribed or using illicit substances (as determined via urine drug screen and screening interview)
• Use of marijuana or THC products more than once monthly on average
• Subjects with contra-indications to MR imaging, including pacemakers or severe claustrophobia, and/or size incompatible with scanner gantry, e. g., men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.
• Suicidal thoughts with plans or intentions, as assessed by C-SSRS
• Any other condition or criteria that would preclude safe and meaningful participation in this study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Nicolaas Bohnen, MD, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nicolaas Bohnen, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

Domino's Farms

Ann Arbor, Michigan, United States

University Hospital

Ann Arbor, Michigan, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HUM00227568

Identifier Type: -

Identifier Source: org_study_id