Evaluating the Impact of Ketogenic Therapy on Symptom Severity and Metabolic Side Effect Profile Among Individuals Living With Bipolar Disorder in A Rural Southern Catchment Area

Evaluating the Impact of Ketogenic Therapy on Symptom Severity and Metabolic Side Effect Profile Among Individuals Living With Bipolar Disorder in A Rural Southern Catchment Area - A Four-Arm Pilot Study

It is the purpose of this pilot study to evaluate a high-fat/low-carbohydrate "ketogenic" diet-based intervention as an adjunctive strategy for impacting symptoms of bipolar disorder. The study is designed to evaluate this impact in the rural southern catchment area around Montgomery, Alabama.

While existing access and cost barriers can prevent effective treatment of bipolar disorder in the rural south, using food as medicine represents a possible alternative/adjunctive to traditional high-cost/low-access medications. Specifically, this study will evaluate the impact of combining a ketogenic diet with existing treatment options, under the conditions of the rural catchment area, to determine the impact and efficacy of this intervention at patient and systems levels.

If effective, the interventions examined in this pilot study may increase the efficacy, availability and access to care experienced by individuals living with bipolarity in the rural Deep South.

Study Overview

• Status: Not yet recruiting
• Conditions: Bipolar Disorder
• Intervention / Treatment: Other: Standard of Care Oral antipsychotics; Other: Standard of care long acting injectable medication for bipolar disorder; Dietary supplement: Ketogenic foodstuffs

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Will Rutland, MD; Phone Number: 334-747-7550; Email: wrutland@uab.edu

Study Locations

• United States
  • Alabama
    • Montgomery, Alabama, United States, 36116-2496
      • Baptist Medical Center South
      • Contact: Will Rutland, MD; Phone Number: 3347477550; Email: wrutland@uab.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18
• Verified Bipolar Diagnosis per NETSCID

Exclusion Criteria:

• Acute psychiatric instability (manic episode, active suicidality requiring hospitalization)
• Anorexia
• Pregnancy
• Severe renal insufficiency
• Hepatic insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral bipolar medication only; Participants in this arm will receive oral medication treatment as usual for bipolar disorder. These medications may include second generation antipsychotic mood stabilizing medications aripiprazole, risperidone, quetiapine, and olanzapine.	Other: Standard of Care Oral antipsychotics; Oral mood stabilizing antipsychotics for the treatment of bipolar disorder. These medications may include second generation antipsychotic mood stabilizing medications aripiprazole, risperidone, quetiapine, and olanzapine.
Active Comparator: Long-acting injectable medication only; Participants in this arm will receive long-acting injectable medication as treatment for bipolar disorder. This medication may include aripiprazole monohydrate.	Other: Standard of care long acting injectable medication for bipolar disorder; Long-acting injectable antipsychotic mood stabilizing medication for bipolar disorder. The medication used may include aripiprazole monohydrate.
Experimental: Oral medication + ketogenic diet; Participants in this arm will receive oral medication for bipolar disorder, plus foodstuffs necessary to support ketogenic diet. Oral medications may include second generation antipsychotic mood stabilizing medications aripiprazole, risperidone, quetiapine, and olanzapine.	Other: Standard of Care Oral antipsychotics; Oral mood stabilizing antipsychotics for the treatment of bipolar disorder. These medications may include second generation antipsychotic mood stabilizing medications aripiprazole, risperidone, quetiapine, and olanzapine.; Dietary supplement: Ketogenic foodstuffs; Weekly food box, selected from rotating menu of three options, as designed by study dietician to include ketogenic foodstuffs.
Experimental: Long-acting injectable medication + ketogenic diet; Participants in this arm will receive long-acting injectable medication for bipolar disorder, plus foodstuffs necessary to support ketogenic diet. The medication used may include aripiprazole monohydrate.	Other: Standard of care long acting injectable medication for bipolar disorder; Long-acting injectable antipsychotic mood stabilizing medication for bipolar disorder. The medication used may include aripiprazole monohydrate.; Dietary supplement: Ketogenic foodstuffs; Weekly food box, selected from rotating menu of three options, as designed by study dietician to include ketogenic foodstuffs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact on Symptom Severity as measured by Young Mania Ratings Scale	The Young Mania Rating Scale (YMRS) is a clinical assessment tool specifically designed to evaluate manic symptoms and their severity. The YMRS comprises 11 items. Each item is rated on a scale that varies in range, typically from 0 to 4 or 0 to 8, allowing for a nuanced measurement of symptoms. The total score can range from 0 to 60, with higher scores indicating more severe manic symptoms.	T0 (time of intake); T0+1 week; T0+2 weeks; T0+3 weeks; T0+4 weeks; T0+6 weeks; T0+8 weeks; T0+10 weeks; T0+12 weeks; T0+16 weeks; T0+20 weeks; T0+24 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Baszucki Family Foundation; Baptist Health System Montgomery
• Investigators: Principal Investigator: Will Rutland, MD, UAB Heersink School of Medicine - Montgomery Psychiatry

Publications and helpful links

General Publications

• Yildiz, A., Siafis, S., Mavridis, D., Vieta, E., & Leucht, S. (2023). Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis. The lancet. Psychiatry, 10(9), 693-705. https://doi.org/10.1016/S2215-0366(23)00199-2
• Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., Westman, E., Krauss, R. M., & Saslow, L. (2024). Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry research, 335, 115866. https://doi.org/10.1016/j.psychres.2024.115866
• Kishi, T., Ikuta, T., Matsuda, Y., Sakuma, K., Okuya, M., Nomura, I., Hatano, M., & Iwata, N. (2022). Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials. Molecular psychiatry, 27(2), 1136-1144. https://doi.org/10.1038/s41380-021-01334-4

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: May 1, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ketogenic; rural; long-acting injectable
• Additional Relevant MeSH Terms: Bipolar and Related Disorders; Mental Disorders; Mood Disorders; Bipolar Disorder; MD1
• Other Study ID Numbers: IRB-300016223; PF-2025-025 (Other Grant/Funding Number: Baszucki Family Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No