Ketogenic Diet in People With Schizophrenia

NCT05968638 | Active Not Recruiting DMC

• 1 other identifier: HP-00106193
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Schizophrenia is a serious mental disorder with a heterogenous presentation, lack of clear understanding of pathophysiology and only partially effective treatments. First-line antipsychotic drugs block dopamine, but many people continue to suffer from persistent positive or negative symptoms that cannot be fully treated with available medications. Recently, our group has found that dietary modulations have efficacy comparable to antipsychotic medications and that determining which patients could benefit from a personalized treatment framework is critical. The ketogenic diet consists of low-carbohydrate, moderate protein and high fat intake inducing a state in which ketone bodies in the blood provide energy to the cells. In pharmacologic mouse models a ketogenic diet regimen resulted in complete restoration of normal behaviors, independent of strict caloric restriction and other work has suggested that a ketogenic diet may improve schizophrenia like deficits in rodents. An open label ketogenic diet study in the 1950s reported improvement in schizophrenia symptom. At least 7 additional case reports have found robust improvements or complete resolution of schizophrenia symptoms. Recently a retrospective study found robust and significant improvements in schizophrenia symptoms in 10 schizoaffective disorder patients treated with a ketogenic diet. In addition to psychiatric symptoms, improvements in metabolic outcomes have been demonstrated. However, to date, there have been no published double blind randomized controlled trials evaluating the effects of a ketogenic diet since few sites can conduct inpatient trials and have observation and control for food intake

Conditions

Schizophrenia; Schizo Affective Disorder

Outcome Measures

Primary Outcomes (1)

• Assessment of positive and negative symptoms

  Brief Psychiatric Rating Scale (BPRS): The BPRS scale will be the primary outcome measure. It will be administered at baseline and at the end of each week. The BPRS is considered the most widely used symptom rating scale in psychiatric research, is highly sensitive to change, and has excellent interrater reliability with appropriate training of raters. The BPRS assesses the level of 18 symptom constructs such as hostility, suspiciousness, hallucination, and grandiosity. The rater enters a number for each symptom construct that ranges from 1 (not present) to 7 (extremely severe). The score ranges from 18-126, with the higher the number the worse the symptoms.

  3 months

Study Arms (2)

Regular Diet

PLACEBO COMPARATOR

Other: Regular Diet

Ketogenic Diet

ACTIVE COMPARATOR

Other: Ketogenic Diet

Interventions

Regular Diet OTHER

Regular Diet

Regular Diet

Ketogenic Diet OTHER

Ketogenic Diet

Ketogenic Diet

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18- 64 years
• Diagnostic and Statistical Manual (DSM-IV/DSM 5) diagnosis of schizophrenia or schizoaffective disorder
• Antipsychotic regimen with no dose change in last 14 days
• Minimum score of 45 on BPRS
• Body mass index \> 18.5
• Ability to consent determined by a score of 10 or greater on the Evaluation to Sign Consent.

You may not qualify if:

• Pregnant or lactating females
• Type I diabetes or insulin dependent Type II diabetes
• Current diagnosis of DSM 5 eating disorder
• Heart failure
• corrected QT interval (QTc) prolongation greater than or equal to 500ms
• Significant kidney disease
• Indicators for possible acute kidney injury (AKI) or moderate chronic kidney disease (CKD) based on some factors below. Each is not used individually but a clinician will determine based on the following:
• Creatinine \> 1.3mg/dL
• Glomerular Filtration Rate (GFR) \< 60 mL/min/1.73 m2
• Renal tubular disorders
• History of kidney transplantation
• Significant liver disease.
• Indicators for possible acute or chronic liver disease. Each is not used individually but a clinician will determine based on the following:
• Prolonged International Normalized Ratio (INR) greater than or equal to 1.5, elevated bilirubin and aminotransferases (3x normal upper limit) and/or Complete Blood Count (CBC) abnormalities (thrombocytopenia, anemia)
• Physical examination abnormalities (jaundice, icteric sclera, asterixis)

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Maryland Psychiatric Research Center (MPRC) Treatment Research Program (TRP)

Catonsville, Maryland, 21228, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Diet; Diet, Ketogenic

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics

Study Officials

• Deanna L Kelly, Pharm.D., BCPP

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: single-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief and Director, Treatment Research Program

Model Details: Participants will be assigned to receive either a ketogenic diet or regular diet

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: August 1, 2023
• Study Start: September 1, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: November 12, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)