Ketosis Impact on Signs & Symptoms of Schizophrenia and Bipolar disorderS

NCT06426134 | Completed DMC

• 2 other identifiers: NL83836.018.232024.0100
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if a ketone drink can improve signs and symptoms of patients with a schizophrenia-spectrum disorder (SSD), or a bipolar-spectrum disorder (BD). The main questions it aims to answer are: Does a ketone drink improve information processing in patients with SSD/BD? Other questions it aims to answer are: Does a ketone drink improve cognitive functioning in patients with SSD/BD? Does a ketone drink improve metabolism and inflammation in patients with SSD/BD? Does a ketone drink affect circadian rhythm in patients with SSD/BD? Research will compare the effects of the ketone drink with that of an isocaloric carbohydrate drink in the same patients ('cross-over'). Participants will:

• EEG/EMG to determine information-processing parameters (PPI and P300)
• cognitive tests
• visual analog scale of mood, energy levels, ability to focus
• indirect calorimetry to determine use of energy substrate
• blood draws
• for 5 consecutive days:
• wear a continuous glucose monitor (CGM)
• wear a non-invasive passive sweat biomarker sensor (EnLiSense device)
• register a diet and nicotine diary
• saliva sampling (max. 5x/day)

Conditions

Schizophrenia and Related Disorders; Psychosis; Bipolar and Related Disorders; Manic Episode; Depressive Episode

Outcome Measures

Primary Outcomes (1)

• Prepulse Inhibition (PPI) - change dGK vs isocaloric control

  PPI: an event-related potential (ERP) representing information processing (known to be disrupted in schizophrenia and bipolar disorder). The PPI task is an auditory paradigm featuring a total of 10 trials split evenly into two conditions: prepulse (PP) and non-prepulse (NP) in blocks. Startle pulses are 100dB at 40 ms, which is shown to provide significant startle visible in EEG126. Prepulse stimuli are 70 dB and 50 ms in duration, presented 50ms prior to the startle pulse. There is a 12 to 18 (avg: 15 s) interstimulus interval. All stimuli are white-noise blips. A calibrated apparatus is used to present the stimuli. Total estimated time is 20 min.

  measured 45 minutes (Tmax) after ingestion of intervention 1 (dGK) and 45 minuts after ingestion of intervention 2 (isocaloric carb control)

Secondary Outcomes (15)

• P300 Event Related Potential (change dGK vs isocaloric control)

  measured 65-75 minutes after ingestion of intervention 1 (dGK) and 75 minutes after ingestion of intervention 2 (isocaloric carb control); NB: directly after PPI.

• Cognitive test: 15 Word Test (15WT) - change dGK vs isocaloric control

  measured 75-85 minutes after ingestion of intervention 1 (dGK) and 75 minutes after ingestion of intervention 2 (isocaloric carb control); NB: directly after P300.

• Cognitive test: Trail Making Test A (TMT-A) - change dGK vs isocaloric control

  measured 75-85 minutes after ingestion of intervention 1 (dGK) and 75 minutes after ingestion of intervention 2 (isocaloric carb control); NB: directly after P300.

• Cognitive test: Trail-Making Test B (TMT-B) - (change dGK vs isocaloric control)

  measured 75-85 minutes after ingestion of intervention 1 (dGK) and 75 minutes after ingestion of intervention 2 (isocaloric carb control); NB: directly after TMT-A.

• Cognitive test: Digit Span Test (DST) (change dGK vs isocaloric control)

  measured 75-85 minutes after ingestion of intervention 1 (dGK) and 75 minutes after ingestion of intervention 2 (isocaloric carb control); NB: directly after TMT-B.

Study Arms (2)

dGK

EXPERIMENTAL

1x50 g dGK ketone drink

Dietary Supplement: (R)-3-hydroxybutyl (R)-3-hydroxybutyrate)

isocaloric carb control

ACTIVE COMPARATOR

1x isocaloric carbohydrate control drink

Other: Maltodextrin, Fructose, Pectin, Sodium alginate, Sodium chloride

Interventions

(R)-3-hydroxybutyl (R)-3-hydroxybutyrate) DIETARY_SUPPLEMENT

1x50g ingestion of pure dGK

Also known as: delta G Ketones (dGK)

dGK

Maltodextrin, Fructose, Pectin, Sodium alginate, Sodium chloride OTHER

Isocaloric carbohydrate control (active control)

Also known as: Maurten Drink Mix 160

isocaloric carb control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a first-episode psychosis (underlying schizophrenia-spectrum disorder), or patients with a (hypo)manic or depressive episode (underlying bipolar disorder)
• Age \>= 18 years old
• Receiving standard care (including antipsychotic and mood stabilizing medication)
• Mentally competent to give informed consent:

You may not qualify if:

• Substance use as cause of psychosis or (hypo)mania
• Substance use (other than nicotine) in the week prior to study onset
• Intellectual disability
• Diabetes mellitus (type 1 or type 2)
• Metabolic disease impacting ketone metabolism (NB: these are rare disorders diagnosed during childhood)
• Liver disease
• Kidney disease
• Cardiovascular disease
• Pregnancy
• Breastfeeding

Sponsors & Collaborators

• Parnassia Groep: collaborator
• The University of Texas at Dallas: collaborator
• University of Alberta: collaborator
• EnLiSense: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC, dept. Psychiatry

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Related Publications (1)

• Dielemans DA, Yurtkap Y, van der Pluijm M, Soeters MR, Oranje B, Smit DJ, Ziermans T, van Tricht MJ, Muthukumar S, Prasad S, van der Mieden van Opmeer RL, Dekeyster E, Kamperman AM, Dyck JR, Rosema BS, Hoekstra R, Kupka RW, de Haan L, van Beveren NJ, Huizer K. The Effect of Exogenous Ketones on Signs and Symptoms of Schizophrenia Spectrum and Bipolar Disorders: Study Protocol for a Triple-Blind, Randomized, Controlled Crossover Pilot Study. Curr Dev Nutr. 2025 May 24;9(6):107480. doi: 10.1016/j.cdnut.2025.107480. eCollection 2025 Jun.

  PMID: 40568354 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Bipolar and Related Disorders; Mania

Interventions

(R)-3-hydroxybutyl (R)-3-hydroxybutyrate; maltodextrin; Fructose; Pectins; Alginates; Sodium Chloride

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Mood Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Plant Extracts; Plant Preparations; Biological Products; Complex Mixtures; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Karin Huizer, MD/PhD

  Parnassia Groep

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator; MD, PhD

Study Record Dates

• First Submitted: May 8, 2024
• First Posted: May 23, 2024
• Study Start: December 1, 2024
• Primary Completion: April 17, 2026
• Study Completion: April 17, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

NL (1)