Clinical trial NCT06426134: Ketosis Impact on Signs & Symptoms of Schizophrenia and Bipolar disorderS
Official title: Pilot Study on Ketosis Impact on Signs and Symptoms of Schizophrenia and Bipolar Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Schizophrenia and Related Disorders
Psychosis
Bipolar and Related Disorders
Manic Episode
Depressive Episode
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Parnassia Groep
name: The University of Texas at Dallas
name: University of Alberta
name: EnLiSense
First posted: 2024-05-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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:

1. drink a ketone drink and (after a wash-out period) an isocaloric control drink (randomized order); after each drink:

   * 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
2. 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)


Eligibility criteria: Inclusion Criteria:

* 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:

Exclusion Criteria:

* 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

Primary outcomes:
measure: Prepulse Inhibition (PPI) - change dGK vs isocaloric control
timeFrame: measured 45 minutes (Tmax) after ingestion of intervention 1 (dGK) and 45 minuts after ingestion of intervention 2 (isocaloric carb control)
Secondary outcomes:
measure: P300 Event Related Potential (change dGK vs isocaloric control)
timeFrame: 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.
measure: Cognitive test: 15 Word Test (15WT) - change dGK vs isocaloric control
timeFrame: 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.
measure: Cognitive test: Trail Making Test A (TMT-A) - change dGK vs isocaloric control
timeFrame: 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.
measure: Cognitive test: Trail-Making Test B (TMT-B) - (change dGK vs isocaloric control)
timeFrame: 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.
measure: Cognitive test: Digit Span Test (DST) (change dGK vs isocaloric control)
timeFrame: 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.
measure: Patient experience outcome on Mood, energy level, focus (change dGK vs isocaloric control)
timeFrame: measured circa 120 minutes after ingestion of intervention 1 (dGK) and circa 120 minutes after ingestion of intervention 2 (isocaloric carb control)
measure: Immune function: blood markers (change dGK vs isocaloric control)
timeFrame: first blood sample before ingestion (dGK or isocaloric control) (T0), then every 20 minutes in first hour after ingestion; afterwards every 30 minutes (max. 3 hours)
measure: Immune function: blood RNA markers (change dGK vs isocaloric control)
timeFrame: first blood sample before ingestion (dGK or isocaloric control) (T0), next at T0+90 minutes
measure: Immune function: passive sweat IL-6 (change dGK vs isocaloric control)
timeFrame: Full 5 days of the study
measure: Immune function: passive sweat TNF-a (change dGK vs isocaloric control)
timeFrame: Full 5 days of study
measure: Metabolic function: Indirect Calorimetry (change dGK vs isocaloric control)
timeFrame: circa 90-120 minutes after ingestion of intervention 1 (dGK) and intervention 2 (isocaloric control); directly after finalizing cognitive tests.
measure: Metabolic function: blood biomarkers - change dGK vs isocaloric control
timeFrame: first blood sample before ingestion (both dGK and isocaloric control) (T0), then every 20 minutes in first hour after ingestion; afterwards every 30 minutes (max. 3 hours)
measure: Metabolic function: continuous glucose monitor (CGM) - change dGK vs isocaloric control
timeFrame: Full 5 days of the study.
measure: Circadian rhythm: passive sweat cortisol (change dGK vs isocaloric control)
timeFrame: Full 5 days of study
measure: Circadian rhythm: passive sweat melatonin (change dGK vs isocaloric control)
timeFrame: Full 5 days of study
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, dept. Psychiatry
state: Noord-Holland
Study officials:
affiliation: Parnassia Groep
name: Karin Huizer, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: