Brain Small Chain Fatty Acid Metabolism in Bipolar Disorder: Ketones

Bipolar Disorder Clinical Trial

— BIPO  

Official title:

Brain Small Chain Fatty Acid Metabolism in Bipolar Disorder: Ketones

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06335875
• Other study ID #: HUM00227568
• Status: Recruiting
• Phase: N/A
• Start date: May 2024
• Est. completion date: March 2027

Study information

• Verified date: May 2024
• Source: University of Michigan
• Contact: Rob Vangel, BSc
• Phone: 734-936-1168
• Email: rvangel[@]med.umich.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: March 2027
• Est. primary completion date: March 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bipolar Disorder

Intervention

Dietary Supplement:
• 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

Behavioral:
• 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.

Locations

Country	Name	City	State
United States	Domino's Farms	Ann Arbor	Michigan
United States	University Hospital	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in blood beta-hydroxybutyrate level	Keto-Mojo devices will be used to measure blood beta-hydroxybutyrate levels at baseline and after taking the supplement to assess both immediate and sustained effects on blood beta-hydroxybutyrate. Measurements taken at baseline, mid-intervention, and post-intervention will be compared and regressed to analyze associated changes.	After 90 +/- 10 days of intervention
Secondary	Change in blood glucose lability	Continuous glucose monitoring (CGM) devices will be used to capture blood glucose lability, defined as frequency of glycemic spiking averaged per day. Baseline blood glucose lability and post-intervention blood glucose lability will be compared to analyze associated changes.	After 90 +/- 10 days of intervention
Secondary	Change in neural network stability	Functional Magnetic Resonance Imaging (fMRI) will be used to measure neural network stability (defined by correlations and anticorrelations among brain regions over time. Computed neural network stability after the supplementation/dietary change period will be compared to computed neural network stability at baseline.	After 90 +/- 10 days of intervention