Elucidating Neurobiological Mechanisms Underlying the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder (BD): a Multidisciplinary Mechanistic Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 107
- 试验地点
- 2
- 主要终点
- Fasting hepatic function panel at Baseline: bilirubin
研究概览
简要总结
The investigators aim to examine the effect of the ketogenic diet on brain activity, metabolism, and emotions in adults with Bipolar Disorder (BD).
详细描述
The investigators hypothesize that a ketogenic diet will enhance levels of the ketone body β-Hydroxybutyrate (beta OHB), resulting in reduced mania/hypomania severity and predisposition to mania/hypomania in individuals with BD. To test this hypothesis in depth, the investigators will use a novel, multidisciplinary mechanistic study using multimodal neuroimaging, peripheral markers of mitochondrial metabolism, and participant-derived induced pluripotent stem cell (iPSC)-derived organoids.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All participants:
- •18-40 years of age
- •Not following a ketogenic diet
- •BD hypomanic group (n=30):
- •Meeting sex proportion: 50% female
- •Meeting diagnosis proportion: 50:50% Bipolar I: Bipolar II (BDI:II) (Diagnostic and Statistical Manual of Mental Disorders 5; DSM-5)
- •Score greater than 10 on the Young Mania Rating Scale score(YMRS)
- •BD medications will be allowed as in our previous studies: any combination of atypical antipsychotics, lithium, antidepressants, anxiolytics (common in BD)
- •BD euthymic group (n=30):
- •Meeting sex proportion: 50% female
- •Meeting diagnosis proportion: 50:50% BDI:II (DSM-5)
- •Score less than or equal to 10 on YMRS
- •BD medications will be allowed as in our previous studies: any combination of atypical antipsychotics, lithium, antidepressants, anxiolytics (common in BD)
- •Healthy Control (HC) Group (n=30):
- •Sex matched with BD groups
- •No psychiatric history
排除标准
- •All participants:
- •Not between 18-40 years of age
- •History of head injury, neurological, pervasive developmental disorder (e.g. autism), systemic medical disease and treatment (medical records, participant report)
- •Mini-Mental State Examination score (cognitive state) <24
- •Premorbid National Adult Reading Test Intelligent Quotient (NAART IQ) estimate<85
- •Visual disturbance: <20/40 Snellen visual acuity
- •History of alcohol/substance use disorder (SUD; all substances, including nicotine), and/or illicit substance use (except cannabis) over the last 6 months (SCID-5). Note: lifetime/present cannabis use (at non-abuse (<3 times in the past month) and non SUD levels) will be allowed, given its common usage in BD and young adults. Cannabis SUD over the last 6 months will not be allowed. Urine tests on scan days will exclude current illicit substance use (except cannabis). Salivary alcohol tests on scan days will exclude intoxicated individuals
- •MRI exclusion: metallic objects, e.g., surgical implants; claustrophobia; positive pregnancy test for females or self-report pregnancy
- •Unable to understand English
- •Conditions related to the pancreas, liver, thyroid or gallbladder.
- •Taking anticoagulants and/or those with blood dyscrasias (illnesses) who have coagulation disorders (eg, hemophilia) because of the ketomojo finger stick blood tests
- •Scoring 3 or higher on positive symptom factor questions on the Positive and Negative Syndrome Scale (PANSS) questionnaire (indicative of psychotic symptoms)
- •Currently following a ketogenic diet
- •Head circumference larger than 24 inches (62cm) and/or chest circumference larger than 55 inches (139 cm)
- •BD hypomanic group:
- •Must be meeting sex proportions: not 50% female
- •Must be meeting diagnosis proportions: not 50:50% BDI:II (DSM-5)
- •Diagnosis of BD in a manic or euthymic episode
- •Score 10 or lower on the Young Mania Rating Scale score(YMRS)
- •Using psychotropic medications other than those allowed in inclusion criteria
- •Does not have a smartphone with a) iOS version 12.0 or above, or b) Android version 8 and later to use with the Keto-Mojo app
- •BD euthymic group:
- •Not meeting sex proportion: not 50% female
- •Not meeting diagnosis proportion: not 50:50% BDI:II
- •Diagnosis of BD in a depressive, hypomanic, or manic episode
- •Score greater than 10 on YMRS
- •Using psychotropic medications other than those allowed in inclusion criteria
- •Does not have a smartphone with a) iOS version 12.0 or above, or b) Android version 8 and later to use with the Keto-Mojo app
- •Healthy Control (HC) Group
- •Not sex-matched with BD groups
- •Has psychiatric history
结局指标
主要结局
Fasting hepatic function panel at Baseline: bilirubin
时间窗: Baseline (all participants)
Fasting levels of bilirubin in the blood
Blood oxygen level-dependent (BOLD) signal at Scan 3
时间窗: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
The blood oxygen level-dependent (BOLD) signal indicates brain activity and connectivity
Manic symptoms at Scan 1
时间窗: Baseline Scan 1 (all participants)
The Young Mania Rating Scale (YMRS) indicates the level of manic symptoms with a total score that varies between zero (better outcome) and 60 (worse outcome)
Manic symptoms at Scan 3
时间窗: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
The Young Mania Rating Scale (YMRS) indicates the level of manic symptoms with a total score that varies between zero (better outcome) and 60 (worse outcome)
Fasting lipids at Baseline
时间窗: Baseline (all participants)
Fasting lipid blood levels
Fasting Glucose at end of second dietary phase
时间窗: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting glucose blood levels
Fasting Glucose at Baseline
时间窗: Baseline (all participants)
Fasting glucose blood levels
Blood oxygen level-dependent (BOLD) signal at Scan 1
时间窗: Baseline Scan 1 (all participants)
The blood oxygen level-dependent (BOLD) signal indicates brain activity and connectivity
Fasting hepatic function panel at Baseline: total protein
时间窗: Baseline (all participants)
Fasting levels of total protein in the blood
Fasting hepatic function panel at Baseline: albumin
时间窗: Baseline (all participants)
Fasting levels of albumin in the blood
Fasting Glucose at halfway point through first dietary phase
时间窗: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting glucose blood levels
Fasting hepatic function at end of first dietary phase: total protein
时间窗: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of total protein in the blood
Fasting hepatic function panel at Baseline: liver enzyme
时间窗: Baseline (all participants)
Fasting levels of liver enzyme in the blood
Fasting lipids at halfway point through first dietary phase
时间窗: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting lipid blood levels
Fasting hepatic function at halfway point through first dietary phase: liver enzyme
时间窗: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of liver enzyme in the blood
Fasting lipids at end of first dietary phase
时间窗: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting lipid blood levels
Fasting hepatic function at end of first dietary phase: liver enzyme
时间窗: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of liver enzyme in the blood
Fasting Glucose at halfway point through second dietary phase
时间窗: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting glucose blood levels
Fasting hepatic function at halfway point through second dietary phase: albumin
时间窗: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of albumin in the blood
Blood oxygen level-dependent (BOLD) signal at Scan 2
时间窗: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
The blood oxygen level-dependent (BOLD) signal indicates brain activity and connectivity
Manic symptoms at Scan 2
时间窗: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
The Young Mania Rating Scale (YMRS) indicates the level of manic symptoms with a total score that varies between zero (better outcome) and 60 (worse outcome)
Fasting hepatic function at halfway point through first dietary phase: total protein
时间窗: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of total protein in the blood
Fasting Glucose at end of first dietary phase
时间窗: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting glucose blood levels
Fasting hepatic function at end of first dietary phase: bilirubin
时间窗: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of bilirubin in the blood
Fasting lipids at halfway point through second dietary phase
时间窗: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting lipid blood levels
Fasting hepatic function at halfway point through second dietary phase: total protein
时间窗: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of total protein in the blood
Fasting hepatic function at halfway point through first dietary phase: albumin
时间窗: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of albumin in the blood
Fasting hepatic function at halfway point through first dietary phase: bilirubin
时间窗: Halfway point through first dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of bilirubin in the blood
Fasting hepatic function at halfway point through second dietary phase: liver enzyme
时间窗: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of liver enzyme in the blood
Fasting hepatic function at end of second dietary phase: total protein
时间窗: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of total protein in the blood
Fasting hepatic function at end of second dietary phase: albumin
时间窗: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of albumin in the blood
Fasting hepatic function at end of second dietary phase: liver enzyme
时间窗: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of liver enzyme in the blood
Fasting hepatic function at end of first dietary phase: albumin
时间窗: End of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of albumin in the blood
Lactate at Baseline
时间窗: Baseline Scan 1 (all participants)
Lactate concentrations in the brain
Lactate at end of first dietary phase
时间窗: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Lactate concentrations in the brain
Glutamate at end of first dietary phase
时间窗: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Glutamate concentrations in the brain
Fasting hepatic function at halfway point through second dietary phase: bilirubin
时间窗: Halfway point through second dietary phase (4-5 weeks) (participants with Bipolar Disorder)
Fasting levels of bilirubin in the blood
Fasting hepatic function at end of second dietary phase: bilirubin
时间窗: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting levels of bilirubin in the blood
Gamma-aminobutyric acid (GABA) at Baseline
时间窗: Baseline Scan 1 (all participants)
Gamma-aminobutyric acid (GABA) concentrations in the brain
Glutamate at end of second dietary phase
时间窗: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Glutamate concentrations in the brain
Lactate at end of second dietary phase
时间窗: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Lactate concentrations in the brain
Fasting lipids at end of second dietary phase
时间窗: End of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Fasting lipids blood levels
Gamma-aminobutyric acid (GABA) at end of first dietary phase
时间窗: Scan 2 at end of first dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Gamma-aminobutyric acid (GABA) concentrations in the brain
Glutamate at Baseline
时间窗: Baseline Scan 1 (all participants)
Glutamate concentrations in the brain
Gamma-aminobutyric acid (GABA) at end of second dietary phase
时间窗: Scan 3 at end of second dietary phase (8-10 weeks) (participants with Bipolar Disorder)
Gamma-aminobutyric acid (GABA) concentrations in the brain
次要结局
- Average total sleep time during Ketogenic vs Normal diet(Wrist actigraphy will be collected throughout the 8-10wk ketogenic diet and normal diet study intervals)
- Ecological momentary assessments (EMA) during the second dietary phase: Suicidality monitoring(The second dietary phase (8-10 weeks) (participants with Bipolar Disorder))
- Average rest-activity rhythm interdaily stability during Ketogenic vs Normal diet(Wrist actigraphy will be collected throughout the 8-10 wk ketogenic diet and normal diet study intervals.)
- Ecological momentary assessments (EMA) during the first dietary phase: Mood monitoring(The first dietary phase (8-10 weeks) (participants with Bipolar Disorder))
- Ecological momentary assessments (EMA) during the second dietary phase: Mood monitoring(The second dietary phase (8-10 weeks) (participants with Bipolar Disorder))
- Ecological momentary assessments (EMA) during the second dietary phase: Energy monitoring(The second dietary phase (8-10 weeks) (participants with Bipolar Disorder))
- Ecological momentary assessments (EMA) during the first dietary phase: Suicidality monitoring(The first dietary phase (8-10 weeks) (participants with Bipolar Disorder))
- Ecological momentary assessments (EMA) during the first dietary phase: Energy monitoring(The first dietary phase (8-10 weeks) (participants with Bipolar Disorder))
研究者
Mary Phillips, MD MD (Cantab)
Professor
University of Pittsburgh