Recovery With Exogenous Ketones and Antipsychotics

NCT ID: NCT07122531

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-25
• Study Completion Date: 2027-08-15

Brief Summary

The RECAP project will evaluate the clinical and metabolic effects of adding exogenous ketones to antipsychotic (AP) treatment in young adults with a first episode of psychosis (FEP).

FEP requires early intervention to limit relapse, chronic symptoms, cognitive decline, and reduced life expectancy. Symptoms include positive (hallucinations, delusions), negative (amotivation, anhedonia), cognitive (attention, working memory), and mood disturbances. Standard care combines second- or third-generation APs with psychosocial interventions. However, many patients have persistent symptoms despite optimal treatment.

Psychosis is linked to increased cardiovascular and obesity risk. APs can cause insulin resistance, type 2 diabetes, and dyslipidemia, but some metabolic abnormalities-both systemic and cerebral-may precede AP use, suggesting an intrinsic metabolic dysfunction. Brain energy metabolism is often impaired, with altered insulin signaling, glucose transport, and ATP production. Glucose hypometabolism in the prefrontal cortex correlates with negative and cognitive symptoms, even before medication, resembling patterns in Alzheimer's, bipolar disorder, and depression.

Ketones, especially beta-hydroxybutyrate, provide an alternative to glucose for brain energy. Ketogenic diets have therapeutic potential but are difficult to maintain, particularly in psychiatric populations. Exogenous ketones, such as medium-chain triglycerides (MCTs), can raise circulating ketone levels without major dietary changes. MCT supplementation has been shown to improve brain metabolism and cognition in other conditions, but no studies have tested it in FEP.

This uncontrolled, prospective pilot study will provide 15 g of MCT oil twice daily for 12 weeks, in addition to participants' usual diet and treatment. The primary objective is to assess changes in circulating ketone levels and metabolic markers (glucose, insulin, HbA1c). Secondary objectives include feasibility, acceptability, effects on real-time glucose metabolism (via continuous glucose monitoring), clinical symptoms (negative, cognitive), quality of life, other metabolic biomarkers, and general systemic markers.

This is the first study to test exogenous ketones in FEP. It will assess safety, tolerability, and potential metabolic and clinical benefits, offering preliminary mechanistic insights and guiding future integrative mental health strategies.

Conditions

First Episode Psychosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

12 week ketogenic supplementation

Supplementation with 15 g of medium chain triglyceride oil, emulsified in beverage of choice, twice daily (morning and evening) for 12 weeks,.

Group Type: EXPERIMENTAL

Medium chain triglyceride oil

Intervention Type: OTHER

Supplementation with 15 g of medium chain triglyceride oil, a food product commercially available over-the-counter in regular grocery stores, emulsified in beverage of choice, twice daily (morning and evening) for 12 weeks.

Interventions

Medium chain triglyceride oil

Supplementation with 15 g of medium chain triglyceride oil, a food product commercially available over-the-counter in regular grocery stores, emulsified in beverage of choice, twice daily (morning and evening) for 12 weeks.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Referred or self-referred to the PEP Clinic of the Estrie region, either as an outpatient or inpatient.
• Currently receiving a second- or third-generation antipsychotic at a stable dose for at least 4 weeks.
• Able to read and communicate in French or English.
• Capable of understanding and signing the informed consent form.

Exclusion Criteria

• Pregnancy, childbirth within the past 6 months, or breastfeeding.
• any use of MCT oil, ketone salts, or a ketogenic diet within the past year.
• Previous diagnosis of type I or type II diabetes.
• Uncontrolled acute suicidal ideation at the time of inclusion in the PEP clinic.
• Other conditions that may interfere with participation, as determined by the qualified physician.
• Pancreatitis (inflammation of the pancreas) or liver failure.
• Metabolic condition affecting fat metabolism or inherited carnitine deficiency and its related enzymes.
• Porphyria.
• Pyruvate kinase deficiency.
• Neurodevelopmental disorder of unknown etiology or rare genetic disease.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Université de Sherbrooke

OTHER

Sponsor Role: lead

Responsible Party

Stephen Cunnane

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kevin Zemmour, MD

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke

Locations

Hotel-Dieu CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, Canada

Countries

Canada

Central Contacts

Melanie Fortier, M.Sc

Role: CONTACT

melanie.melf@gmail.com

1-819-821-5206

Stephen Cunnane, PhD

Role: CONTACT

stephen.cunnane@usherbrooke.ca

1-819-780-2220 ext. 45670

Facility Contacts

Melanie Fortier, MSc

Role: primary

melanie.fortier2@usherbrooke.ca

1-819-821-5206

Other Identifiers

2025 -5840

Identifier Type: -

Identifier Source: org_study_id