Recovery With Exogenous Ketones and Antipsychotics

NCT07122531 | Not Yet Recruiting

• 1 other identifier: 2025 -5840
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Keywords

first episode psychosis; Schizophrenia; metabolism; ketone; medium triglyceride; antipsychosis; glucose

Outcome Measures

Primary Outcomes (4)

• Plasma total ketones concentration

  Change in plasma total ketone (acetoacetate + betahydroxybutyrate) after 12 weeks of supplementation (uM)

  12 weeks

• Plasmatic glucose concentration

  Change in glucose concentration (mM) after 12 weeks of supplementation (uM)

  12 weeks

• Plasma Insulin concentraiton

  Change in insuline concentration (UI) after 12 weeks of supplementation (uM)

  12 weeks

• Plasma Glycated hemoglobin

  Change in Glycated hemoglobin (%) after 12 weeks of supplementation

  12 weeks

Secondary Outcomes (10)

• acceptability of exogenous ketone supplementation

  at the end of the 12 weeks treatment

• compliance rate

  during 12 weeks intervention

• Adverse event rate

  12 weeks intervention

• Drop-out rate

  After 12 weeks of intervention

• Glucose average (mean of glucose measured by continuous glucose monitoring)

  12 weeks

Study Arms (1)

12 week ketogenic supplementation

EXPERIMENTAL

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

Other: Medium chain triglyceride oil

Interventions

Medium chain triglyceride oil 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.

12 week ketogenic supplementation

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Université de Sherbrooke: lead

Study Sites (1)

Hotel-Dieu CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, J1H 4C4, Canada

Location

MeSH Terms

Conditions

Schizophrenia; Ketosis

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Kevin Zemmour, MD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melanie Fortier, M.Sc

CONTACT

1-819-821-5206; melanie.melf@gmail.com

Stephen Cunnane, PhD

CONTACT

1-819-780-2220; stephen.cunnane@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Uncontrolled prospective pilot study.

Study Record Dates

• First Submitted: August 5, 2025
• First Posted: August 14, 2025
• Study Start: August 25, 2025
• Primary Completion (Estimated): April 15, 2027
• Study Completion (Estimated): August 15, 2027
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)