Pilot Study on Ketosis Impact on Signs and Symptoms of Schizophrenia and Bipolar Disorders
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Prepulse Inhibition (PPI) - change dGK vs isocaloric control
研究概览
简要总结
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:
- 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
- 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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
排除标准
- •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
结局指标
主要结局
Prepulse Inhibition (PPI) - change dGK vs isocaloric control
时间窗: measured 45 minutes (Tmax) after ingestion of intervention 1 (dGK) and 45 minuts after ingestion of intervention 2 (isocaloric carb 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.
次要结局
- 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.)
- Immune function: blood markers (change dGK vs isocaloric control)(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))
- Circadian rhythm: passive sweat cortisol (change dGK vs isocaloric control)(Full 5 days of study)
- Circadian rhythm: passive sweat melatonin (change dGK vs isocaloric control)(Full 5 days of study)
- 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.)
- Patient experience outcome on Mood, energy level, focus (change dGK vs isocaloric control)(measured circa 120 minutes after ingestion of intervention 1 (dGK) and circa 120 minutes after ingestion of intervention 2 (isocaloric carb control))
- Immune function: blood RNA markers (change dGK vs isocaloric control)(first blood sample before ingestion (dGK or isocaloric control) (T0), next at T0+90 minutes)
- Immune function: passive sweat IL-6 (change dGK vs isocaloric control)(Full 5 days of the study)
- Immune function: passive sweat TNF-a (change dGK vs isocaloric control)(Full 5 days of study)
- 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.)
- Metabolic function: Indirect Calorimetry (change dGK vs isocaloric control)(circa 90-120 minutes after ingestion of intervention 1 (dGK) and intervention 2 (isocaloric control); directly after finalizing cognitive tests.)
- Metabolic function: continuous glucose monitor (CGM) - change dGK vs isocaloric control(Full 5 days of the study.)
- 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.)
- Metabolic function: blood biomarkers - change dGK vs isocaloric control(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))
研究者
Karin Huizer
Principal Investigator; MD, PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)