Strategies to Augment Ketosis: Ketone Conferred Resiliency Against Sleep Restriction
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Gradual-onset Continuous Performance Task (GRAD-CPT
研究概览
简要总结
Sleep deprivation is a major problem in military populations. Some major consequences of sleep loss are inability to concentrate, poor work efficiency, and increase in errors during daily tasks. There is some evidence that ketone ester supplements may lessen the adverse effects of sleep restriction. The main purpose of these supplements is to raise your blood concentration of ketones, which are safe, small molecules that appear in the blood during fasting, when following a ketogenic diet, or consuming ketone supplements.
The main purpose of this study is to examine if ingesting a ketone ester supplement, twice daily, can improve cognitive and physical performance during short-term sleep restriction.
详细描述
Only 1 in 3 U.S. Army Active Component Soldiers are estimated to get the target =7-hr of sleep on duty days, and ~14% have a sleep disorder. Insufficient sleep has profound effects on human performance that include deficits in working memory, creativity, innovative thinking, strategic planning, mood disturbances, lapses in attention and vigilance, and impaired physical performance. In a classic dose-response sleep study performed at Walter Reed Army Institute of Research, it was demonstrated that limiting sleep to 3-hr per night for 7-days resulted in a steady deterioration on a psychomotor vigilance task across the week of sleep restriction. Sleep restriction over 3-days has been shown to adversely affect marksmanship performance, including significantly longer time to make decisions, misidentifying friends versus foes, and believing performance did not change over time. Short-term sleep restriction is linked with impaired glucose metabolism and decreased whole body insulin sensitivity, and increases the risk of developing T2D. Military personnel have few good options to counteract physical and cognitive detriments attributed to insufficient sleep. Warfighters increasingly turn to caffeine and sugar-containing energy drinks to combat sleep loss and fatigue, especially during deployment. At best, these nutritional countermeasures provide a transient performance gain, and may trigger a 'rebound' hypoglycemia that exacerbates performance detriments that can increase the risk of obesity and related problems. Ketosis could improve tolerance to sleep restriction and sleep abnormalities through multiple mechanisms. We have reported that a 1-yr KD improved sleep quality and the proportion of people categorized as poor sleepers. Ketones are a preferred brain fuel that may enhance neurocognitive function. The ability to metabolize a lipid-derived substrate (ketones) capable of sustaining the brain's high energy demands during periods with limited access to carbohydrate was a central adaptation in human evolution, that is also associated with a remarkable protection from the adverse signs of hypoglycemia. At the low end of nutritional ketosis (0.5 mM), ~5% of whole brain energy metabolism is provided by ketones. At ketone concentrations of 1.5 mM (typical of KDs), ketones supply nearly 20%; at the higher end of nutritional ketosis 4-5 mM [achievable with ketone esters (KE)], half of the brain energy demands are met by ketones. Importantly in situations where brain glucose metabolism is impaired, uptake and utilization of ketones remain fully intact, suggesting a hierarchy of importance placed on ketones as the preferred fuel for human brains.
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
- Double (Participant, Investigator)
盲法说明
Study product will be distributed in a blinded manner by people not involved with testing.
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
- •Participant is willing and able to comply with all study procedures including the following prior to Test Days: fasting (>10 h; water only), no alcohol (>24 h), no exercise (>24 h), no acute illness and controlled feeding before each Test Day, maintain diet, exercise, medication, and supplement habits throughout the study.
- •Participant has no health conditions that would prevent completion of the study requirements as judged by the Investigator based on health history.
- •Participant understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Investigator.
排除标准
- •<18 or >40 years of age
- •>35 body mass index (BMI).
- •Diagnosed sleeping disorders (i.e., sleep apnea, insomnia).
- •Gastrointestinal disorders or food allergies that would interfere with consuming the study supplements.
- •Drink alcohol in excess of 3 drinks/day or 14 drinks/week
- •Have any conditions or contraindications to blood draws.
- •Have been diagnosed with diabetes, liver, kidney, or other metabolic or endocrine dysfunction, or use diabetic medications other than metformin
- •Currently consume a low carbohydrate or ketogenic diet or have done so in the last 3 months
- •Have experienced weight loss of >10% of your body weight within the last 6 months
- •Are pregnant, lactating, or planning on becoming pregnant during the study
- •Have any major psychiatric disorders (e.g., schizophrenia, bipolar disorder)
研究组 & 干预措施
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Sleep Deprivation (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Heart Rate (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Sleep Monitoring (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Diet (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Exercise Performance (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Surveys, McGill Pain Questionnaire, Shortened Profile of Mood States, Pittsburg Sleep Index (Behavioral)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Cognitive performance (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Surveys, McGill Pain Questionnaire, Shortened Profile of Mood States, Pittsburg Sleep Index (Behavioral)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Marksmanship Performance (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Quick Board (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Advanced Medical Technologies Inc, Jump Test (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: CGM/CKM (Other)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Blood Draw (Biological)
Placebo First
Patients will be randomize to take the placebo for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a ketone ester.
干预措施: Ketone Supplement (Dietary Supplement)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Sleep Deprivation (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Heart Rate (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Sleep Monitoring (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Diet (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Exercise Performance (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Cognitive performance (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Marksmanship Performance (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Quick Board (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Advanced Medical Technologies Inc, Jump Test (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: CGM/CKM (Other)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Blood Draw (Biological)
Ketone Ester First
Patients will be randomize to take the ketone ester for the first trial of the intervention, then after a 2 week washout, participants will perform the same intervention but with a placebo
干预措施: Ketone Supplement (Dietary Supplement)
结局指标
主要结局
Gradual-onset Continuous Performance Task (GRAD-CPT
时间窗: Up to ~4 weeks
This test measures endogenous attentional control by using smooth (rather than abrupt) transitions between visual images. Scene stimuli are visually presented and smoothly transition from one scene to another. Subjects press a button when one type of scene is presented (e.g., city scene) and withhold the button press when another type of scene (e.g., mountain scene) is presented. It is a Go/No-Go test and assesses multiple metrics of executive function, including sustained attention, mind wandering, and response inhibition.
Face-Name Task
时间窗: Up to ~4 weeks
We will implement a face-name relational memory task, known to activate the hippocampus (along with prefrontal and parietal cortices) in humans using face-name pairs presented for 3-sec with an interval of 750-msec. Participants will judge which name was previously presented with the face. After a 15-min delay, participants will complete an associative face-name recognition task to assess episodic memory performance.
Shot Group Tightness
时间窗: Up to ~4 weeks
The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Shot group tightness, a metric of marksmanship, will be collected during each visit to assess multi-shot accuracy.
Power Outcome (QuickBoard)
时间窗: Up to ~4 weeks
Upper body and lower body reaction tests will be assess using Quick Board Analysis on days 1 and 5 of the sleep restriction intervention.
Total number of shots fired
时间窗: Up to ~4 weeks
The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Total number of shots fired, a metric of marksmanship, will be collected during each visit, to assess reaction time and accuracy.
Cambridge Neuropsychological Test Automated Battery. (CANTAB)
时间窗: Up to ~ 4 Weeks
This iPad delivery assessment will include an Information Sampling Task to test impulsivity and decision making, response time (in msec), which provides a level of sensitivity not available with traditional paper and pencil tasks, processing speed, executive functioning, and spatial memory. We have also incorporated tasks which assess the ability to rapidly identify expressed facial emotions, which may index one's ability to accurately respond to overtly threatening or non-threatening stimuli
Time from target presentation to trigger pull
时间窗: Up to ~4 weeks
The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Time from target presentation to trigger pull, a metric of marksmanship , will be collected during each visit to assess reaction time.
Automated Neuropsychological Assessment Metrics (ANAM)
时间窗: Up to ~ 4 weeks
This cognitive battery is a library of computer-based tests of domains including attention, concentration, reaction time, memory, processing speed, decision-making, and executive function.
Percentage of targets successfully hit per minute
时间窗: Up to ~4 weeks
The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. Percentage of targets successfully hit/min, a metric of marksmanship, will be collected during each visit to assess accuracy.
Radial distance of a shot from the center on target
时间窗: Up to ~4 weeks
The Virtual Training Simulator (VirTra V-100) system (VirTra Corporate HQ, Tempe, AZ) is used by both military and law enforcement agencies to provide training. The V-100 and associated compatible weapons are equipped with recoil kits for unsurpassed live-fire simulation, at distances up to 2,000-m, authoring capabilities for the creation of customized scenarios on 4 individual firing lanes. The radial distance of a shot from the center on target, a metric of marksmanship, will be collected during each visit to assess shot accuracy.
次要结局
- Insulin(Up to ~ 4 weeks)
- Brain Derived Neurotropic Factor(Up to ~4 weeks)
- CGM/CKM(Up to ~ 4 weeks)
- Heart Rate(Up to ~ 4 weeks)
- Ghrelin(Up to ~ 4 weeks)
- Profile of Mood States- Short Form(Up to ~ 4 weeks)
- CRP(Up to ~ 4 weeks)
- Short Form- McGill Pain Questionnaire(Up to ~ 4 weeks)
- Pittsburgh Sleep Quality Index(Up to ~ 4 weeks)
研究者
Jeff Volek
Professor
Ohio State University