Recovery With Exogenous Ketones and Antipsychotics

Официальное название

Metabolic and Clinical Evaluation of Medium-Chain Triglyceride-Based Exogenous Ketone Supplementation as an Adjunctive Treatment for First-Episode Psychosis

Обзор

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.

Вмешательства

• Другое 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.

Первичные конечные точки

• Plasma total ketones concentration [Срок оценки: 12 weeks]
• Plasmatic glucose concentration [Срок оценки: 12 weeks]
• Plasma Insulin concentraiton [Срок оценки: 12 weeks]
• Plasma Glycated hemoglobin [Срок оценки: 12 weeks]

Вторичные конечные точки (10)

• acceptability of exogenous ketone supplementation [Срок оценки: at the end of the 12 weeks treatment]
• compliance rate [Срок оценки: during 12 weeks intervention]
• Adverse event rate [Срок оценки: 12 weeks intervention]
• Drop-out rate [Срок оценки: After 12 weeks of intervention]
• Glucose average (mean of glucose measured by continuous glucose monitoring) [Срок оценки: 12 weeks]
• glucose variability (SD of glucose measured by continuous glucose monitoring) [Срок оценки: 12 weeks]
• Negative symptomes [Срок оценки: 12 weeks]
• Depression status measured by the score of "Calgary Depression Scale for Schizophrenia [Срок оценки: 12 weeks]
• Brief Assessment of Cognition (BACS) [Срок оценки: 12 weeks]
• Functionning level measured by the score of the Global Assessment of functionning [Срок оценки: 12 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Hotel-Dieu CIUSSS de l'Estrie-CHUS — Sherbrooke

Идентификаторы

NCT: NCT07122531 · 2025 -5840

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗