Ketogenic Diet in People With Schizophrenia

NCT ID: NCT05968638

Last Updated: 2025-11-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-01
• Study Completion Date: 2027-08-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Regular Diet

Group Type: PLACEBO_COMPARATOR

Regular Diet

Intervention Type: OTHER

Regular Diet

Ketogenic Diet

Group Type: ACTIVE_COMPARATOR

Ketogenic Diet

Intervention Type: OTHER

Ketogenic Diet

Interventions

Regular Diet

Regular Diet

Intervention Type: OTHER

Ketogenic Diet

Ketogenic Diet

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age 18- 64 years

2. Diagnostic and Statistical Manual (DSM-IV/DSM 5) diagnosis of schizophrenia or schizoaffective disorder

3. Antipsychotic regimen with no dose change in last 14 days

4. Minimum score of 45 on BPRS

5. Body mass index > 18.5

6. Ability to consent determined by a score of 10 or greater on the Evaluation to Sign Consent.

Exclusion Criteria

1. Pregnant or lactating females

2. Type I diabetes or insulin dependent Type II diabetes

3. Current diagnosis of DSM 5 eating disorder

4. Heart failure

5. corrected QT interval (QTc) prolongation greater than or equal to 500ms

6. 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

7. 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)
• Alcohol use disorder (AUD) based on DSM 5 criteria for moderate AUD
• History of liver disease (cirrhosis, Wilson disease, Gilbert disease, chronic hepatitis, autoimmune hepatitis, primary biliary cirrhosis (PBC), primary Sclerosing Cholangitis (PSC) alpha-1 antitrypsin deficiency, hereditary hemochromatosis, Budd-Chiari syndrome)
• History of liver transplantation

8. Porphyria

9. Genetic disorders that affect fat metabolism (Gaucher disease, Tay-Sachs disease, medium-chain acyl-CoA dehydrogenase deficiency (MCADD)

10. Carnitine deficiency syndromes (primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency)

11. Pyruvate kinase deficiency

12. Gastroparesis

13. Refusal to eat intervention diet, food allergies or restrictions that the kitchen cannot accommodate, and/or dietary noncompliance with dietary energy needs

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Deanna Kelly

Chief and Director, Treatment Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Deanna L Kelly, Pharm.D., BCPP

Role: PRINCIPAL_INVESTIGATOR

Study Principal Investigator

Locations

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

Catonsville, Maryland, United States

Countries

United States

Other Identifiers

HP-00106193

Identifier Type: -

Identifier Source: org_study_id