How the schizophrenia brain uses ketones and glucose

Keto-Brain: Cerebral Energy Substrate Metabolism in First-Episode Schizophrenia

This project will use PET scans to see if ketone and glucose use in the brain changes in people aged 18–35 who are newly diagnosed with schizophrenia before and after starting antipsychotic treatment, compared with healthy controls.

Quick facts

• Study type: Observational
• Enrollment: 34 (estimated)
• Ages: 18 Years to 35 Years
• Sex: All
• Sponsor: University of Aarhus (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Aarhus)
• Trial ID: NCT07309172 on ClinicalTrials.gov

What this trial studies

This is a non-interventional PET neuroimaging pilot that measures brain ketone and glucose metabolism in antipsychotic-naïve first-episode schizophrenia patients and matched healthy controls. Patients undergo PET imaging at baseline before starting antipsychotics and again after 4–8 weeks of treatment, with an additional clinical follow-up at six months, while controls have a single baseline visit. The investigators aim to recruit 22 patients to allow for an expected 50% dropout and obtain about 12 full datasets. The study focuses on metabolic substrate use (ketone bodies versus glucose) to characterize early illness changes and short-term effects of antipsychotic exposure.

Who should consider this trial

Good fit: Ideal candidates are people aged 18–35 with a first-episode, antipsychotic-naïve schizophrenia diagnosis and age/sex-matched healthy volunteers without psychiatric disorders who can give informed consent.

Not a fit: People with prior antipsychotic exposure beyond the limited allowed doses, those under coercive/forensic care, individuals with intellectual disability, or those outside the 18–35 age range are unlikely to qualify or benefit from the study findings.

Why it matters

Potential benefit: If successful, the study could reveal metabolic differences that lead to new treatment approaches or metabolic adjuncts to improve symptoms or brain health in schizophrenia.

How similar studies have performed: This specific before-and-after measurement of brain ketone metabolism in schizophrenia is novel, although PET studies of brain glucose metabolism in psychiatric disorders have precedent.

Eligibility criteria

Inclusion Criteria:

Inclusion criteria for patients with FES

1. Age 18-35 years
2. Diagnosed with FES (ICD-10: F20)
3. Able to give informed oral and written consent.

Inclusion criteria for healthy controls

1. Age 18-35 years
2. No mental disorder (ICD-10: F00-99)
3. Able to give informed oral and written consent.

Exclusion Criteria:

Exclusion criteria for patients with FES

1. Any coercive measure including patients in forensic psychiatry
2. In a clinical condition where the treating clinician evaluates that the patient is not able to attend the research study.
3. Previous use of AP at an antipsychotic dose (except for Risperidone ≤0.5 mg, Abilify ≤2.5 mg, Seroquel ≤50 mg or Zyprexa ≤2.5 mg) for more than 2 continuous weeks in the past year and/or 6 weeks over a lifetime
4. Use of an antipsychotic in the last 3 months before inclusion at a dose greater than:

   4.1 Seroquel/Quetiapine 50 mg 4.2 Risperdal/Risperidone 0.5 mg
5. Comorbidity: Borderline intelligence or intellectual disability, autism spectrum disorder, decompensated substance use disorder, psychosis induced by a medical condition or psychosis induced by medication or drug use.
6. Pregnancy, childbirth within the past 6 months, or breastfeeding. Female participants should use an effective contraception.
7. Contraindications to MRI (metal, severe claustrophobia).
8. Acute suicidal thoughts (e.g., resulting in hospitalization)
9. Diabetes mellitus type 1. History of severe head trauma, stroke, chemotherapy or brain surgery. Hypo- or hyperthyroidism. Epilepsy. Systemic glucocorticoid hormone treatment.
10. Other conditions interfering with participation according to the qualified physician's judgment.

Exclusion criteria for healthy controls

1. Previous use of an antipsychotic dose (except for Risperidone ≤0.5 mg, Abilify ≤2.5 mg, Seroquel ≤50 mg or Zyprexa ≤2.5 mg) for more than 2 continuous weeks in the past year and/or 6 weeks over a lifetime
2. Use of AP in the last 3 months before inclusion at a dose greater than:

   1. Seroquel/Quetiapine 50 mg
   2. Risperdal/Risperidone 0.5 mg
3. Pregnancy, childbirth within the past 6 months, or breastfeeding. Female participants should use an effective contraception.
4. Contraindications to MRI (metal, severe claustrophobia).
5. Diabetes mellitus type 1. History of severe head trauma, stroke, chemotherapy or brain surgery. Hypo- or hyperthyroidism. Epilepsy. Systemic glucocorticoid hormone treatment.
6. Other conditions interfering with participation according to the qualified physician's judgment.

Where this trial is running

Aarhus

• Aarhus University Hospital, Psychosis Research Unit — Aarhus, Denmark (Recruiting)

Study contacts

• Study coordinator: Ole Köhler-Forsberg, MD, PhD, DMSc

Conditions Schizophrenia Disorder; Schizophrenia; PET neuroimaging; Brain energy substrate metabolism; Ketone bodies; Glucose