Child Bipolar Network Ketogenic Diet Approach to Bipolar Disorder in Adolescents
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 4
- 主要终点
- Diet Adherence
研究概览
简要总结
The present study is an open trial of ketogenic diets for adolescents and young adults (ages 12-21 yrs) in the depressive or mixed phases of bipolar disorder (BD). The investigators aim to determine whether combining standard of care pharmacological treatment for bipolar spectrum disorders with a 16-week ketogenic diet is well-tolerated and associated with improvements in depression, inflammatory and metabolic indicators, and executive functioning over the study period.
The experimental treatment in this study is a 16-week full ketogenic diet. Four study sites (UCLA, U Cincinnati, U Colorado and U Pittsburgh) will recruit 80 total youth (20 each) from bipolar specialty clinics. All youth eligible for the ketogenic therapy will be provided with the ketogenic diet and standard of care pharmacological treatment. During the diet therapy youth will be seen by a study child/adolescent psychiatrist at least once a month (and more frequently when needed), with the psychiatrist recommending and providing side effects monitoring and pharmacotherapy as clinically indicated.
The youth and caregivers will also meet with an expert dietitian who will coach all youth on maintaining the ketogenic diet (low carbs, high fats, medium protein) and making sure the child is tolerating the diet and getting enough liquid and nutrients, following the practice guidelines of the International Ketogenic Diet Study Group for treating youth. All youth and involved caregivers will also be provided will at least one motivational enhancement session to support them in goal setting and completion of the study elements.
Throughout the study the investigators will assess metabolic (e.g., blood ketones, HOMA-IR) and inflammatory indicators (e.g., C-reactive protein), both for safety reasons and to assess correlates of symptomatic change. Independent evaluators will assess youth every month regarding their symptoms (depression, mania, anxiety, psychosis), psychosocial functioning, and quality of life.
The investigators anticipate that the pilot will transpire over 24 months and be an important step toward establishing feasibility and acceptability of ketogenic therapy for this population, not only in terms of diet administration and compliance but also for obtaining symptomatic, metabolic and inflammatory measurements.
详细描述
Site PIs David Miklowitz, Ph.D., Distinguished Professor of Psychiatry, University of California, Los Angeles
Danella Hafeman, M.D. and Boris Birmaher, MD, University of Pittsburgh School of Medicine;
Christopher Schneck MD (site PI), Melissa Batt, MD (co-PI), and Aimee Sullivan, PhD, University of Colorado Anschutz Medical Campus, Aurora, CO.
Melissa Delbello, MD (site PI) and L. Rodrigo Patino Duran, MD (Co-PI), University of Cincinnati College of Medicine
Phase 1: Intake Period and Pre-Treatment Assessments
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Youth must be ages 12 to 21 years old and speak English
- •Youth must be appropriate for outpatient treatment (i.e., not a danger to self or others; not acutely psychotic, suicidal or manic; not in need of partial or full hospitalization)
- •Youth must have a current BSD (bipolar I, II per DSM-5 criteria (Association, 2013) or other specified BSD by the University of Pittsburgh diagnostic criteria (Birmaher et al., 2006). The Pittsburgh other specified BSD criteria require recurrent and distinct 1-3 day periods (minimum 4 hours/day) in which there has been abnormally elevated, expansive, or irritable mood plus two (three, if irritable mood only) symptoms of mania that caused a change in functioning and totaled at least 4 days in the child's lifetime
- •Active symptoms: In the 2 weeks prior to study intake, participants must have had weekly depression Psychiatric Status Ratings (PSRs) of 3 (moderate) or higher (using the 1-6 depression severity scales from the Adolescent Longitudinal Follow-up Evaluation, or A-LIFE); or an interview-based Children's Depression Rating Scale, Revised (CDRS-R) score covering the prior 2 weeks of >
- •Youth may also enter with mixed symptoms (e.g., simultaneous elevations of > 3 on the PSR depression and hypomania scales, with Young Mania Rating Scale scores of 12 or higher), without meeting criteria for a full manic episode in the past month.
- •Participants must continue to meet the study's active symptom criteria when beginning the phase II keto "ramp-up" phase: a depression PSR rating of 3 or higher over the prior 2 weeks, and a CDRS-R score covering the prior 2 weeks of >
- •Youth/parents must be willing to participate in evaluation and medication management sessions with a study psychiatrist and the study dietitian for assessment of the diet and side effects.
- •Youth under 18 years old must have at least one English-speaking parent or other caregiving family member consenting to participate in the study and available for consultation if needed
- •Youth and (for minors) all parents/legal guardians with health care decision making rights must express willingness to have the youth be in the study and try the keto therapy, assuming that the youth is eligible. The team must ascertain that the participating minor's youth/caregiver is likely to make a strong effort to adhere to the study's protocol.
排除标准
- •The youth must not have any of the following needs or conditions for which the keto diet may be contraindicated:
- •pregnancy or breastfeeding
- •underweight (BMI below 18.5) or wasting syndrome (e.g., anorexia cachexia)
- •current or history of anorexia nervosa
- •current disordered eating (bulimia or binge eating disorder)
- •autism spectrum disorder diagnosis level 2 or greater (more than mild)
- •cardiac issues, including history of arrhythmia, or cardiovascular or cerebrovascular disease
- •type I and type II diabetes
- •history of seizures/epilepsy
- •history of stroke or cancer
- •unstable respiratory condition
- •severe gastroesophageal reflux (GERD; painful/impairing despite prescription medication)
- •substance use disorder (with an exception for mild cannabis or nicotine use disorders)
- •history of kidney stones/disease
- •diseases involving the pancreas, liver, gallbladder or thyroid, including Von Gierke's glycogen storage disease
- •Condition with high cholesterol of triglycerides will prompt physician review of eligibility (LDL>190 or triglycerides>500)
- •genetic metabolic disorders: either porphyria (impacting the body's ability to make hemoglobin) or fatty acid oxidation disorder (FAOD)
- •rare conditions of defective ketone production or breakdown (carnitine deficiency, carnitine palmitoyl-transferase deficiency, carnitine-acylcarnitine translocase deficiency, mitochondrial fatty acid β-oxidation disorders, Succinyl-CoA:3-ketoacid CoA transferase deficiency (SCOT), or pyruvate carboxylase deficiency)
- •youth must not be taking SGLT-2 inhibitors (e.g., canagliflozin), insulin, or sulfonylureas (to avoid hypogycemia), or Antihypertensive medication (e.g., lisinopril/ACE Angiotensin inhibitors ending in "pril", ARB Angiotensin II receptor blockers, spironolactone/Aldactone, Thiazide-type diuretics)
研究组 & 干预措施
Ketogenic Therapy for Bipolar Spectrum Disorders
This is a pilot trial with one intervention arm. All youth meeting eligibility for the ketogenic therapy phase of this pilot trial will be invited to participate in the intervention and progress tracking.
干预措施: Ketogenic Therapy (Other)
结局指标
主要结局
Diet Adherence
时间窗: From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)
The investigators will assess diet adherence primarily by the proportion of youth who maintain an average weekly ketone level of 1 mmol/L or above, as measured through daily blood ketone assays using the Keto Mojo device, a Bluetooth-enabled ketone and glucose testing kit.
Depression Symptom Improvement
时间窗: From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)
The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant reductions in depressive symptoms from baseline to completion of the diet. Depressive symptoms will primarily be captured using the clinician-rated Children's Depression Rating Scale, Revised (CDRS-R). Scores range from 17 to 113, with higher scores indicating greater pathology or severity of depressive symptoms (worse outcome).
Bipolar Symptom Improvement
时间窗: From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)
The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant reductions in bipolar mood instability from baseline to completion of the diet. Bipolar instability will primarily be captured using the clinician-rated Clinical Global Impression - Bipolar Disorder Severity Scale (CGI-BP). CGI-BP overall psychiatric illness scores range from 1 (normal, best outcome) to 7 (very severely ill, worse outcome) and capture severity of bipolar symptoms over the worst 7-day period in the past 2 weeks.
Diet Tolerance
时间窗: From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)
The investigators will assess diet tolerance primarily by calculating the proportion of youth staying on the diet. The investigators hypothesize 70-80% of youth will tolerate staying on the keto therapy throughout the 16-week treatment as verified by youth self report of continuance of the diet (combined with parent report if applicable). Youth with multiple weekly ketone levels at .5 mmol/L or below will be considered diet intolerant regardless of self-report.
HOMA - IR Metabolic Indicator
时间窗: From initiation of ketogenic therapy to the end of treatment (up to 16 weeks)
The investigators hypothesize that youth with high compliance with the keto diet will show significant pre- to post-treatment improvement in Homeostatic model assessment for insulin resistance (HOMA - IR). HOMA - IR is calculated based on fasting glucose and insulin measurements and a value greater than 2 indicates insulin resistance (worse outcome) while a value less than 1 indicates normal range insulin sensitivity (better outcome).
次要结局
- Youth Functional Improvement(From initiation of ketogenic therapy to the end of treatment (up to 16 weeks))
- Serum Inflammatory Biomarkers (CRP)(From initiation of ketogenic therapy to the end of treatment (up to 16 weeks))
研究者
David J. Miklowitz, Ph.D.
Distinguished Professor of Psychiatry
University of California, Los Angeles