58 Clinical Trials for Various Conditions
The goal of this clinical research study is to test what effects a ketone drink will have in people with heart failure with preserved ejection fraction (HFpEF), including on exercise and heart function. Patients with HFpEF often have difficulty exercising, and our goal is to understand whether a ketone drink changes much patients can exercise. The study has three visits, including a baseline visit to assess for study eligibility, and two visits (one after 8 weeks of a ketone drink or a placebo drink, and another one after 8 weeks of whichever drink the participant did not receive the first time).
One important difference between KE compounds is the ketone-promoting components, which determines the circulating ratio of blood ketone bodies, BHB and AcAc, and may in turn lead to important metabolic and signaling differences. Whereas some actions of the ketone bodies BHB and AcAc are shared, R-BHB has a broad range of signaling functions that are distinct from AcAc, some of which are shared by the non-circulating, non-oxidizable enantiomer, S-BHB. AcAc also has metabolic and signaling actions that are independent of BHB and is selectively oxidized in some cells that cannot oxidize BHB. Furthermore, responses to different ketone bodies vary between tissue types. A second difference between KE arises from the balance between direct delivery of ketones compared to indirectly elevating ketone concentration via metabolism of non-classical or classical ketogenic precursors. Classical ketogenesis itself may drive adaptation and some of the functional benefits associated with ketosis. BDO is included in all of the KE compounds, but it is currently unknown how consumption of BDO alone, and its metabolism via non-classical ketogenesis acutely affects metabolism. Additionally, ketogenesis is now understood to occur in certain cells outside the liver with important local biological effects, for example ketogenesis driven by medium chain fatty acids has been reported in astrocytes in vitro. Provision of systemic BHB by a KE may elicit different biological effects in some tissues such as the brain versus promoting in situ ketogenesis in that tissue. Overall, not only are functional effects of KE incompletely defined, but also it is unknown which effects are common to all KE versus which are specific to an individual KE compound (i.e., BHB Monoester vs AcAc Diester) or which may be attributable to the BDO precursor common to all of the KE. This study will be the first comparative full crossover study of all available KE and the precursor BDO at two serving sizes. Outcomes will focus on established effects of the BHB Monoester (including the effects on ketones, glucose and acid-base balance) and compare these with the effects of the AcAc Diester, C8 Ketonef Diester and BDO.
The scientific goal of this study is to examine the effects of a ketogenic diet on hypoglycemia tolerance and brain function in people with type 1 diabetes mellitus (T1D) and to clarify the mechanistic role of ketones in this process. Glycemic management of T1D is typified by alternating periods of hyper- and hypo-glycemia. Because brain metabolism under usual conditions depends on glucose, acute hypoglycemia leads to immediate complications including impaired cognitive function and a counter-regulatory hormone response. Recurrent hypoglycemia is associated with functional and structural changes in the brain and contributes to the cognitive decline observed in individuals with diabetes. The state of nutritional ketosis (as it occurs during fasting or when following a ketogenic \[very low carbohydrate\] diet) may protect against these acute and chronic complications. As the body relies on fat metabolism, ketone bodies build up and provide an alternative fuel for the brain. Studies during hypoglycemia have shown better cognitive function and less hypoglycemia symptoms in the setting of nutritional ketosis or with ketone administration. This physiological benefit may have special relevance for people with T1D who experience hypoglycemia frequently. To date, no mechanistic studies have examined brain effects of nutritional ketosis in T1D; nor have any trials explored the potential relevance of this for diabetes care.
The primary purpose of this study is to characterize the performance and utility of a novel breath acetone meter developed by Readout, Inc.
The goal of this study is to quantify day-to-day changes in blood glucose during treatment towards remission in ketosis-prone diabetes (KPDM) and describe them using a mathematical model of KPDM pathogenesis and remission.
The goal of this clinical trial is to test how specific components of diet affect brain function and behavior for individuals with bipolar. The main question it aims to answer is how glucose and ketones each affect the brain's response to risk and reward. Participants will be asked to provide blood (to assess baseline measures of how the body uses energy), and then to receive two MRI scan sessions, on separate days. During each MRI scan session, participants will play three games, from which they can win money, before and after drinking glucose (on one day) or ketones (on the other day). Investigators will compare individuals with and without bipolar to test whether the two groups differ in how their brains use energy, and to test how the brain's use of energy affects behavior.
The research study is being conducted in health controls to better understand the effects of ketosis on brain functioning after 3 different, randomly assigned, 3-day dietary interventions and the acute effects of alcohol after consuming about 4-5 alcohol beverages. The labs visits will use magnetic resonance imaging (MRI) scans to study the brain, measuring levels of nicotinamide adenine dinucleotide (NAD), lactate, neurotransmitters glutamate, and Gamma-aminobutyric acid (GABA).
Background: At least 30% of Americans have fatty liver disease. This means that they store too much fat in the liver. At the moment lifestyle changes are the only way to treat this problem. Objective: To test how (1) a low-carbohydrate diet and (2) a supplement called nicotinamide riboside (NR) affect how a person s body uses dietary fat. Eligibility: Men aged 18 to 65 and women aged 18 to 50 who are healthy volunteers with a body mass index (height to weight ratio) of 25 or more. Adults with maturity-onset diabetes of the young type 2 (MODY2) are also needed. Design: Participants with diabetes will have 1 screening visit and a 9-day clinic stay. Healthy volunteers will have 1 screening visit and 2 clinic stays of 1 to 2 weeks each. During screening, all participants will have a physical exam with blood and urine tests. They will have their heart rhythm measured while riding a gym bike. NR is a pill taken by mouth. Only healthy volunteers will take the NR, for 14 days at a time, during 1 clinic stay. During their other stay, they will take placebos; these are pills that look like the study supplement but contain no NR. During each clinic stay, all participants will eat a normal American diet. Then they will eat a ketogenic "low-carb" diet for 5 days. Participants will have many tests, including: Sleeping every night and having two 24-hour stays in a special room that measures the gases their body uses and produces. Drinking a high-fat shake, then remaining seated for 5 hours while their blood and breath are monitored. Having a substance injected into the arm and remaining seated for 3 hours while their blood is measured. Wearing monitors to measure their activity levels. Another monitor will measure their blood glucose levels. Having imaging scans. ...
The purpose of this study is to help us better understand how plasma ketones respond to a low-carb diet when combined with an SGLT2 inhibitor.
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.
Background: The ketogenic diet uses fats as a person's major energy source rather than carbohydrates. There is increasing interest in using this diet to treat neurodegenerative disorders like Parkinson's disease. Researchers want to learn more about the ketogenic diet before recommending this diet in clinical practice. Objective: To study the effects of a ketogenic diet for someone with PD. Eligibility: People over age 50 with mild to moderate PD. Design: Participants will be screened with surveys and a 10-foot walking test. They will have a medical history, physical exam, and blood test. Participants will be contacted twice in a 1-week period to discuss what they ate over the last 24 hours. They will log data about their daily exercise and activities using an online fitness tracking app. Participants will stay at NIH Clinical Center for 1 week. They will be put into 1 of 2 groups. One group will follow a ketogenic diet and take MCT oil. The other group will follow a low-fat diet. Their body measurements will be taken. They will meet with a physical therapist and nutritionist. Participants will have daily respiratory and glucose monitoring. They will have cognitive tests and complete surveys. They will have walking, motor function, and reaction time/finger tapping tests. They will have heart and nerve function tests. They will have electrocardiograms and electroencephalograms. Blood will be taken twice daily. Participants will follow the ketogenic diet at home for 2 weeks. They will log their activities using the fitness tracking app. Then they will have a follow-up visit at NIH. Participation in the trial will last for 4 weeks.
The purpose of this study is to test different methods of preparation that can be used prior to a test called an FDG PET/CT scan. FDG PET/CT scans are routinely done for evaluation of heart inflammation. Standard preparation for the scan includes a ketogenic (high fat and low carbohydrate) diet for 24 hours and overnight fasting to help suppress the amount of sugar taken up in the heart muscle. However, Investigator still do not know if this preparation is the most effective method. So the Investigator, want to investigate alternative methods for decreasing the amount of sugar uptake seen in the heart during FDG PET/CT scan, thus, investigator will have participants try up to 3 different methods of preparation prior to the FDG PET/CT scans to see which type of preparation works the best.
The goal of this proposal is to pilot test our existing very-low carbohydrate diet intervention, adapted for women with PCOS.
The study explores whether selective memory complaints (SMC), mild cognitive impairment (MCI) and the comorbidity of Metabolic Syndrome symptomatic of peripheral and cerebral hypo-metabolism with corresponding epigenetic shifts in global DNA (deoxyribonucleic acid) methylation (away from nutrient availability and toward biosynthesis) are initiated by chronic metabolic inflexibility, over-activation of the mTOR (mammalian target of rapamycin) pathway, and the deregulation of neural oxidative phosphorylation.
Original research article entitled Induced and Controlled Dietary Ketosis as a Regulator of Obesity and Metabolic Syndrome by Madeline Gibas for consideration for publication in a clinical journal. This research manuscript builds on previous landmark studies that report that major weight and fat mass loss in type II (T2D) patients who were fed a very low carbohydrate, ketogenic diet. In this manuscript, the investigators outline our research study that showed statistically significant (p \< 0.05) changes over time in hemoglobin A1c, weight, BMI, body fat percentage and ketones for patients with metabolic syndrome who were fed a very low carbohydrate diet, ketogenic diet.
The study intends on enrolling 48 subjects with diabetes. Diabetic subjects that no longer need insulin will be randomly placed (like the flip of a coin) on a diabetes pill called metformin, a diabetes pill called sitagliptin or a placebo pill (a pill without active medication). Subjects on pills will be followed for 3½ years and undergo blood tests at specified intervals to assess their ability to make insulin. These studies will allow a better understanding of the factors that lead to high blood sugar in patients with ketosis-prone diabetes mellitus (KPDM) and direct the best diabetes treatment for this patient population. Hypothesis: Metformin therapy or sitagliptin therapy compared to placebo, will improve β-cell function, insulin sensitivity, and allow for a longer period of time prior to encountering an insulin-deficient relapse after discontinuation of insulin therapy.
Over 50% of obese African-Americans (AA) presenting with newly diagnosed, severe hyperglycemia and/or unprovoked diabetic ketoacidosis (DKA) display clinical, metabolic, and immunogenetic features of type 2 diabetes. Prior studies indicate that these patients a) have markedly decreased insulin secretion and impaired insulin action at presentation, b) absent or low prevalence of beta-cell autoantibodies and c) are able to discontinue aggressive insulin therapy in \~70% of cases within 3 months of follow-up. These patients have been referred to as having ketosis-prone type 2 diabetes (KPDM). Most patients with KPDM, however, experience a hyperglycemic relapse within a year of insulin discontinuation. Consequently, patients with "KPDM" are an ideal model to follow throughout their clinical course. The specific aims of this proposal are to 1) identify clinical, metabolic, and immunogenetic markers that alone, or in combination, are predictive of short- and long-term near-normoglycemic remission and 2) determine whether pioglitazone or sitagliptin therapy will delay an insulin-deficient relapse once insulin is discontinued. The Principal Investigator hypothesizes that measures of beta-cell function at presentation, alone or in combination with measures of insulin sensitivity, will correlate with the ability of a patient to achieve and remain in near-normoglycemic remission. She also hypothesizes that intervention compared to placebo will preserve beta-cell function, improve insulin sensitivity, and prevent an insulin-deficient relapse. This prospective, cohort study with a RCT arm would better characterize the natural history of KPDM, facilitate the direction of long-term therapy, and likely decrease the recurrence of DKA which is associated with increased mortality and morbidity.
The research study is being conducted to better understand the effects of ketones and alcohol on brain functioning and brain metabolism. Participants will be asked to undergo three identical MRI visits after three single-dose interventions: (1) drink a ketone supplement drink, (2) drink an alcoholic beverage, (3) no intervention. These interventions will be randomly assigned (meaning everyone receives all 3 interventions, but in different orders).
This outcome of this study will elucidate how the phenotype of the individual modulates the KE metabolic effect. Most studies of KE have been in homogenous populations, usually young, male athletes. However, two striking experiments using identical, body weight adjusted KE doses in healthy and obese individuals found that BHB area under the curve (AUC) and removal was reduced by obesity and poor metabolic health. Similarly, ketone infusion experiments found that diabetes, obesity, and insulin resistance alter BHB metabolism. It is important to determine how obesity affects KE 'sensitivity' (i.e., breakdown and oxidation) because the increasing prevalence of obesity as a function of age. Age may be another important source of variation in ketone metabolism. The genes that control the ketone system are regulated by a cascade of transcription factors and hormones including PPARα and FGF21, which are themselves known to be affected by aging and dietary status, and the cellular protein sensor target of rapamycin (TOR). Aberrant hyperactivation of TOR with aging may reduce ketogenesis, while it was observed that a long-term ketogenic diet specifically up-regulated PPARα activity. Preliminary work revealed substantial changes across mouse lifespan in the expression of ketone-related genes in the liver such as Hmgcs2 (rate limiting for ketone production) and Bdh1 (rate limiting for BHB oxidation) between young, middle-aged, and old mice, with a nadir of gene expression in middle age before increasing again late in life. Substantial age differences were found in response to matched doses of oral KE in mice and in rats. These data may have important implications for treating people of different ages and for translating KE technologies into the Department of VA. Therefore, this project plans to study individual responses to KE ingestion across the lifespan, against the background of varying metabolic health
The objective of this randomized crossover study is to examine the influence of consuming a ketone ester plus carbohydrate (KE+CHO) supplement on substrate oxidation and physical performance in 15 healthy adults. Following a 48-hr muscle glycogen normalization period, volunteers will consume either an isocaloric KE+CHO (KE: 573 mg KE/kg body mass, CHO: 110 g) or isocaloric CHO drink and complete 90-min of metabolically-matched, load carriage (\~30% body mass) steady-state aerobic (\~60 ± 5 % of VO2peak) exercise on a treadmill. Glucose tracers will be used to assess glucose turnover, and contribution to exogenous and plasma glucose oxidation. Serial blood draws will be collected during each trial to assess endocrine and circulating substrate responses. After steady-state exercise volunteers will complete a time to exhaustion (TTE) physical performance tests at 85% VO2peak on a treadmill. Volunteers will then be provided with food for the remainder of the day. Following a 10-hr overnight fast, volunteers will return to the laboratory and consume the same supplement (KE+CHO or CHO) as they did the previous day. Volunteers will then perform a 4-mile load carriage time trial on a treadmill. Following a minimum 7-day washout period, volunteers will return to the laboratory to complete the second arm of the study. The primary risks associated with this study include those associated with exercise, blood draws, and gastrointestinal discomfort from the KE+CHO supplement.
Subjects will provide blood and breath samples to evaluate the relationship between breath acetone and two blood-bound species: beta-hydroxybutyrate and glucose. Subjects will be asked to provide breath and blood samples at a baseline visit and second optional visit. The two visits will be spaced approximately 3 hours apart.
The purpose of this study is to determine if intrapartum use of a glucose-containing solution will improve the outcomes in pregnant women and their babies.
Assess the acceptability and tolerability of two different commercially available ketone supplements and determine their effects on capillary blood concentrations of the ketone beta-hydroxybutyrate and glucose in young adults.
This study will test the effect of citrulline versus placebo supplementation in ketosis-prone diabetes (KPD) patients on arginine and nitric oxide production and on glucose- and arginine-stimulated insulin secretion and arterial flow-mediated dilation.
This is a randomized, double-blind, crossover trial to evaluate the immediate effects of a nutritional ketone supplement, Kenotic compared to placebo on brain function and alcohol consumption in individuals with alcohol use disorder. Participants will complete 2 MRI scans, 2 FDG PET/CT scans, and 2 alcohol bar labs and will randomly receive Kenetik at one lab and the placebo at the next lab. During the bar labs participants will consume a dose of alcohol (based on weight), to bring their breath alcohol concentration to about 0.050%.
The goal of this randomized clinical trial is to be adequately powered to evaluate the effect of ketogenic metabolic therapy on the quality of life in serious mental illness, schizophrenia, bipolar disorder, major depressive disorder.
The goal of this clinical trial is to learn the effects of ketone supplement compared to placebo on alcohol withdrawal symptoms during a 4 day alcohol withdrawal management treatment in adults with moderate to severe alcohol use disorder at the Hospital of the University of Pennsylvania, Cedar Detox Center.
The goal of this study is to study the effects of the ketone supplement Kenetik compared to placebo (an inactive beverage) on alcohol withdrawal symptoms during the 5 days of clinical alcohol withdrawal management treatment at the Caron Treatment Center.
The goal of this study is to examine whether a well-formulated ketogenic diet (KD) can be implemented into a university counseling treatment program for major depression and to test whether such a program has any benefit on mental and metabolic health.
The goal of this pilot intervention is to learn about how a well-formulated ketogenic diet (WFKD) impacts various health factors in generally healthy adults. The main questions it aims to answer are: * Establish whether an 8-week isocaloric, WFKD improves body composition and metabolic biomarkers in adults without chronic disease. * Examine changes in transcriptomic sequencing pathways pre- and post-WFKD intervention. * Explore gut microbial changes in adults without chronic disease that consume a WFKD. Participants will follow a well-formulated ketogenic diet for 8-weeks. Study procedures include: * Weekly body weight tracking * Daily urinary ketone assessment * Pre/post stool samples for gut microbiota analyses * Pre/post DXA scans * Diet quality tracking through 3-day food records