Nutritional and Metabolic DiseasesLIME-BNCT07888257
LIfestyle MEtabotype Study B (LIME-B)
A study testing βHB drink (ketone ester) and Carbohydrate drink in people with Nutritional and Metabolic Diseases and Prediabetes, run by German Institute of Human Nutrition at 2 sites in Germany.
Trial summary
Glycemic responses vary significantly among individuals, even when consuming identical foods or meals, but the factors predicting individual glucose responses to food intake remain poorly investigated. Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Nutritional and Metabolic Diseases, Prediabetes, Type 2 Diabetes
- What is being tested?
- βHB drink (ketone ester) and Carbohydrate drink
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 2 sitesGermany
- Study dates
- 26 Oct 2026to 31 Dec 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Overweight or obese (BMI 25-40 kg/m²)
- Good knowledge of German
- Completion of the LIME screening visit; participants who do not take part in the further assessments of module A [NCT07868601] may still participate in module B
- Participants are classified into three groups based on the screening visit:
- Group A (without Prediabetes or Type 2 Diabetes) Criteria: HbA1c <5.7% and fasting plasma glucose < 100 mg/dl
- Group B (Prediabetes) Criteria: HbA1c 5.7-6.4%, or fasting plasma glucose 100-125 mg/dL
- Group C (Type 2 Diabetes) Criteria: HbA1c ≥6.5%, fasting plasma glucose ≥ 126 mg/dl, or existing T2D diagnosis by physician, or T2D diagnosis based on an available result from standardized 75 g oral glucose tolerance test
Who cannot join
- Weight changes of more than 5% in the last 3 months
- Night shift work
- Travel across more than one time zone in the last month before and during study participation
- Intensive regular physical activity of more than 2 hours per day
- Current pregnancy or breastfeeding
- Severe renal, liver or heart disease
Show all 26Show fewer
- Existing or past hematological malignancies, other malignant tumors, unless successfully treated more than 12 months before study start
- Severe neurological or psychiatric disorders
- Daily alcohol consumption of more than 20 grams or more than 150 grams per week
- Use of illicit or legal drugs one week prior to study start and during study participation
- Known systemic infections
- Type 1 diabetes and rare forms of diabetes
- Diabetes treatment with insulin or sulfonylureas or diabetes medication in the absence of manifest type 2 diabetes
- Unstable thyroid dysfunction
- Blood coagulation disorders or anticoagulation therapy that cannot be interrupted
- Medications affecting nutrient absorption
- Medications with immunosuppressants or steroids (oral or parenteral)
- Current eating disorders, functional or structural digestive disorders or bariatric surgery
- Food allergies or intolerances to ingredients of the test meals
- Intermittent fasting or calorie-restricted diet four weeks prior to the start of the study or during the study
- Ketogenic diet or ketogenic supplements four weeks prior to or during module B
- Left-handedness
- Severe claustrophobia
- Electrical implants or non-removable metallic implants
- Concurrent participation in another intervention study
- Assessment by the study physician based on medical concerns precluding study participation
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany2 sites, 2 recruiting
- Recruiting
Freie Universität Berlin, Center for Cognitive Neuroscience Berlin (CCNB)
Berlin, 14195
Eva Fröhlich, Dr., +49 33200 882511, eva.froehlich@dife.de
Soyoung Q Park, Prof. Dr.
- Recruiting
German Institute of Human Nutrition
Nuthetal, 14558
Beeke Peters, MSc, +49 33200 882690, beeke.peters@dife.de
Olga Ramich, Prof. Dr.
About this study
Glycemic responses vary significantly among individuals, even when consuming identical foods or meals, but the factors predicting individual glucose responses to food intake remain poorly investigated. The aim of the LIfestyle MEtabotype (LIME) study is to identify lifestyle-related and mechanistic factors which predict individual postprandial glucose fluctuations in individuals with different glycemic status (prediabetes, type 2 diabetes [T2D] and absence of prediabetes or T2D), using comprehensive lifestyle characterization and metabolic, molecular and neurocognitive phenotyping.
As part of this phenotyping, the LIME study also investigates the role of ketone bodies. Individuals with insulin resistance, prediabetes or T2D often show impaired cerebral glucose utilization. Ketone bodies, such as β-hydroxybutyrate (βHB) may serve as an alternative energy source for the brain. However, how exogenous βHB affects neurocognitive processes and decision-making in individuals with different glycemic status remains poorly understood.
This record describes module B of the LIME study. Module B investigates the effects of a single dose of exogenous βHB, compared with a carbohydrate-based placebo drink, on brain structure and function, decision-making behavior and physiological and metabolic responses. Module A comprises a comprehensive lifestyle and metabolic characterization of the same participants and is registered separately as an observational study (NCT07868601). Data from both modules will be integrated in joint analyses.
Read the detailed description
Studies show that glycemic responses vary significantly among individuals, even when consuming identical foods or meals. These varying glycemic responses are attributed to metabolic differences between individuals. Recently, machine learning models incorporating metabolic data (including microbiome composition) have been able to successfully predict individual blood glucose responses. Precision nutrition recommendations based on such predictions could facilitate better glycemic control and reduce the risk of diabetes. From this perspective, considering metabolic biomarkers, phenotype and genotype, as well as gut microbiome composition, could play a role in deriving dietary recommendations and thereby achieving the best possible health outcomes through nutrition. In addition to macronutrient composition, the timing, frequency and number of meals may also play a significant role in the glycemic response to diet. Finally, socioeconomic, cultural and personal lifestyle factors also have an influence on the glycemic response. Therefore, this study aims to characterize the personal lifestyle differences between individuals with prediabetes, T2D, and those without prediabetes or T2D.
Furthermore, ketone bodies, specifically β-hydroxybutyrate (βHB), are gaining importance, as they serve as both metabolic biomarkers and alternative energy sources in periods of low carbohydrate availability. In individuals with insulin resistance or prediabetes, cerebral glucose utilization is often impaired, leading to the use of ketone bodies as a compensatory energy source for the brain. Findings indicate that the individual ketone response to dietary interventions varies significantly between individuals and could thus itself be relevant as a metabolic phenotype marker in the context of precision nutrition. Therefore, the study also aims to further investigate the extent to which exogenous βHB supplementation influences neurocognitive processes and decision-making behavior, and whether characteristic neurocognitive phenotypes can be derived from this in metabolic risk groups.
This study will achieve its aims by completing a comprehensive lifestyle characterization and metabolic, molecular and neurocognitive phenotyping of individuals with different glycemic status (prediabetes, type 2 diabetes [T2D], and absence of prediabetes or T2D) in a German cohort. The study consists of modules A and B. This record represents a description of module B; module A has an observational design and is registered as a separate record (NCT07868601).
Module A will include a 14-days observational period at home and two visits (screening and phenotyping visits) of the study center at the German Institute of Human Nutrition Potsdam-Rehbrücke before and after the observational period, respectively. Study visits of module A will include an intensive characterization of participants, comprising questionnaires, anthropometric and metabolic assessments, as well as the collection of biological samples. In the observation period, food intake, sleep, activity, and interstitial glucose will be monitored during 14 days, and test meals will be consumed at two days at specific times within this period.
Module B has an interventional crossover design and will take place 1-12 weeks after module A (or after the screening visit for participants not taking part in module A). It includes two visits of the study center at the Freie Universität Berlin, separated by a two-week interval. Study visits of module B will focus on neurocognitive phenotyping, comprising structural and functional magnetic resonance imaging (MRI) of the brain and computer-based decision-making tasks, performed after consumption of either a βHB-containing drink or an equicaloric and taste-matched carbohydrate (dextrose) drink, referred to as placebo drink in the following (test and placebo visits). Data from module A (registered separately [NCT07868601]; e.g., anthropometric and body composition data, blood parameters, CGM-derived glycemic parameters, gut microbiome, lifestyle, metabolic and questionnaire data) will be integrated with module B outcomes to examine associations between individual metabolic and lifestyle phenotypes and neurocognitive, behavioral, affective, physiological and metabolic measures, as well as responses to βHB supplementation. Participants who do not complete the measurements of module A will complete continuous glucose monitoring, actigraphy, sleep and dietary records and stool sample collection between the two module B visits. Module B outcomes will be analyzed with respect to drink condition (βHB vs. placebo), glycemic group, and their interaction.
The aims of the study are as follows:
Primary aims of the LIME study (addressed primarily in module A [NCT07868601], with contributions from module B):
- Identification of metabolic biomarkers and omics-based scores that predict individual glycemic response to food
- Identification of general lifestyle patterns that distinguish individuals with prediabetes or T2D from those without prediabetes or T2D, as well as individuals with prediabetes from those with T2D
- Identification of personal factors and differences in lifestyle patterns that predict individual glucose response to food
Primary aims (LIME-B study):
- Characterization of individual βHB and glucose responses to exogenous βHB supplementation and their association with glycemic status and individual metabolic and lifestyle phenotypes
- Investigation of the effects of exogenous βHB supplementation on neurocognitive processes, cognitive functioning as well as avoidance and decision-making behavior in individuals with different glycemic status
- Elucidation of neuronal, metabolic, and physiological mechanisms associated with specific lifestyle patterns
- Being tested
- βHB drink (ketone ester), Carbohydrate drink
- Keywords
- prediabetes, type 2 diabetes, healthy controls, mri, decision-making, lifestyle factors, ketones, nutritional and metabolic diseases
- Medical subject headings
- Nutritional and Metabolic Diseases, Prediabetic State, Diabetes Mellitus, Type 2, Ketosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
βHB drink (ketone ester)Dietary supplement
Single oral dose of a βHB ester (0.3 g/kg body weight), consumed fasted during one of the two visits of module B
Carbohydrate drinkDietary supplement
Single oral dose of an equicaloric and taste-matched dextrose drink.
| Study group | Role | What they receive |
|---|---|---|
| βHB drink (ketone ester) | Experimental | Participants receive a single dose of a βHB ester drink (0.3 g/kg body weight) at one of the two module B visits Receives: Dietary Supplement: βHB drink (ketone ester) |
| Carbohydrate drink | Active comparator | Carbohydrate drink Participants receive an equicaloric and taste-matched carbohydrate drink (placebo drink) at the other visit of module B Receives: Dietary Supplement: Carbohydrate drink |
What is being measured
The primary outcome is the main question the study is designed to answer.
βHB response to exogenous βHB supplementation
βHB area under the curve (AUC) from fasting and repeated postprandial blood samples after drink intake, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Time course of βHB concentrations
Fasting concentrations and time course of βHB concentrations at individual time points including derived metrics (e.g., peak concentration, time to peak, rate of change), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Fasting and postprandial glucose and insulin response
Fasting concentrations and postprandial time course of glucose, insulin and C-peptide in repeated blood samples after drink intake, including derived metrics (e.g., incremental area under the curve [iAUC], incremental peak, time to peak, amplitude, nadir, rate of change) and indices of insulin sensitivity (e.g., HOMA-IR), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Concentration of inflammatory markers
Interleukin-6 (IL-6) and hsCRP levels measured in fasting blood samples; IL-6 additionally in postprandial blood samples after drink intake, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Metabolic and stress-responsive hormones
Growth differentiation factor 15 (GDF15), fibroblast growth factor 21 (FGF21) and cortisol concentrations in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Gut and appetite-regulating hormones
Glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), ghrelin and leptin concentrations in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Lipolysis and energy metabolites
Free fatty acids, triglycerides, lactate and amino acids in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Oxidative stress markers
Oxidative stress markers such as Malondialdehyde and 3-Nitrotyrosine in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Avoidance behavior
Time spent in less safe areas and exploratory movement in two virtual reality scenarios (elevated platform, dark maze), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Risky decision-making
Choice behavior in a lottery task during fMRI (e.g., proportion of risky choices, risk attitude), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Dual-task performance
Reaction times, accuracy and dual-task costs in an auditory-visual dual-task paradigm, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Heart rate and heart rate variability (HRV)
Heart rate and heart rate variability (HRV) from electrocardiography, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Skin conductance response
Electrodermal activity (EDA) measured via electrodermal activity electrodes, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Respiration rate
Task-based and resting-state respiration rate, measured via a respiration belt pulse (pulse oximetry during MRI), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Pulse
Pulse measured via pulse oximetry during MRI, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Gastric myoelectric activity
Gastric rhythm and power assessed by electrogastrography (EGG), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Brain Structure
Brain morphology (e.g., regional gray matter volume and density) assessed by T1-weighted structural MRI, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
White matter micro- and macrostructure
White matter micro- and macrostructure assessed by diffusion-weighted imaging (DWI), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Resting-state functional connectivity
Functional connectivity between brain regions assessed by resting-state functional MRI (rs-fMRI), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Task-related brain activity
Brain activity during a risk-based decision-making task (lottery task) assessed by functional MRI (fMRI), compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Secondary outcomes (13)
Module A phenotyping data as predictors, moderators and controls
All outcome measures registered for module A [NCT07868601] (e.g., body composition, blood parameters, CGM-derived glycemic parameters, gut microbiome, dietary intake, sleep and activity, questionnaire data) integrated with module B outcomes in joint analyses; if not obtained in module A, CGM, actigraphy, sleep, dietary records and stool samples are collected between the two module B visits
Measured: 2 weeks and 3-16 weeks
Body height
Body height measured using a calibrated wall-mounted measuring tape
Measured: 3-16 weeks
Body weight
Body weight measured by scale weight
Measured: 3-16 weeks
Waist and hip circumference
Waist and hip circumference measured using a measuring tape
Measured: 3-16 weeks
Body Mass Index (BMI)
BMI [kg/m2], calculated as weight/square height
Measured: 3-16 weeks
Subjective state during visits
Repeated ratings of stress, hunger, thirst, anxiety and well-being and subjective hypoglycemia symptoms during the visits, including during the virtual reality task, compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Affective state
Positive and Negative Affect Scale (PANAS; Janke et al., 2014) compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Anxiety
State-Trait Anxiety Inventory (STAI; Grimm et al., 2009) compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Perceived stress
Perceived Stress Questionnaire (PSQ; Fliege et al., 2001) compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Flow state
Flow State Scale (FSS; Rheinberg et al., 2003) compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Food craving
Food Cravings Questionnaire (FCQ; Meule et al., 2012)
Measured: 3-16 weeks
Subjective hypoglycaemic symptoms
Subjective hypoglycaemic symptom list (SHSL; Meyhöfer et al. 2022; Mitrakou et al. 1993) compared between drink conditions (βHB vs. placebo) and glycemic groups
Measured: 3-16 weeks
Other hormones and metabolites (exploratory)
Exploratory analysis of additional hormones and metabolites in stored blood samples (e.g., sex hormones such as testosterone, estradiol, progesterone and sex hormone-binding globulin [SHBG])
Measured: 3-16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2026
- Study start26 Oct 2026 (estimated)
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nutritional and Metabolic DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Within-subject crossover design: each participant receives both the βHB drink and the placebo drink at two visits in module B, separated by an interval of approximately two weeks, in randomized order, stratified by glycemic group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- German Institute of Human Nutrition
- Sponsor type
- University, hospital or other
- Collaborators
- Freie Universität Berlin, Center for Cognitive Neuroscience Berlin (CCNB), German Center of Diabetes Research (DZD)
- Responsible party
- Principal investigator, Prof. Dr. Soyoung Q Park, German Institute of Human Nutrition
- Investigators
- Olga Ramich, Prof. Dr., Principal investigator, German Institute of Human Nutrition Potsdam-Rehbrücke and the Charité - Universitätsmedizin BerlinSoyoung Q Park, Prof. Dr., Principal investigator, German Institute of Human Nutrition Potsdam-Rehbrücke and the Charité - Universitätsmedizin Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07888257
- Sponsor's protocol ID
- 2026-91-BO-ff cf. NCT07868601
- Acronym
- LIME-B
- Status last verified
- Oct 2026
- First submitted
- 15 Oct 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LIfestyle MEtabotype Study B (LIME-B)
- ClinicalTrials.gov ID
- NCT07888257
- Acronym / sponsor ID
- LIME-B / 2026-91-BO-ff cf. NCT07868601
- Keywords
- prediabetes, type 2 diabetes, healthy controls, mri, decision-making, lifestyle factors, ketones, nutritional and metabolic diseases
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- German Institute of Human NutritionUniversity, hospital or other
- Collaborators
- Freie Universität Berlin, Center for Cognitive Neuroscience Berlin (CCNB), German Center of Diabetes Research (DZD)
- Study start
- 26 Oct 2026 (estimated)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 22 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Glycemic responses vary significantly among individuals, even when consuming identical foods or meals, but the factors predicting individual glucose responses to food intake remain poorly investigated. The aim of the LIfestyle MEtabotype (LIME) study is to identify lifestyle-related and mechanistic factors which predict individual postprandial glucose fluctuations in individuals with different glycemic status (prediabetes, type 2 diabetes [T2D] and absence of prediabetes or T2D), using comprehensive lifestyle characterization and metabolic, molecular and neurocognitive phenotyping.
As part of this phenotyping, the LIME study also investigates the role of ketone bodies. Individuals with insulin resistance, prediabetes or T2D often show impaired cerebral glucose utilization. Ketone bodies, such as β-hydroxybutyrate (βHB) may serve as an alternative energy source for the brain. However, how exogenous βHB affects neurocognitive processes and decision-making in individuals with different glycemic status remains poorly understood.
This record describes module B of the LIME study. Module B investigates the effects of a single dose of exogenous βHB, compared with a carbohydrate-based placebo drink, on brain structure and function, decision-making behavior and physiological and metabolic responses. Module A comprises a comprehensive lifestyle and metabolic characterization of the same participants and is registered separately as an observational study (NCT07868601). Data from both modules will be integrated in joint analyses.
Detailed description
Studies show that glycemic responses vary significantly among individuals, even when consuming identical foods or meals. These varying glycemic responses are attributed to metabolic differences between individuals. Recently, machine learning models incorporating metabolic data (including microbiome composition) have been able to successfully predict individual blood glucose responses. Precision nutrition recommendations based on such predictions could facilitate better glycemic control and reduce the risk of diabetes. From this perspective, considering metabolic biomarkers, phenotype and genotype, as well as gut microbiome composition, could play a role in deriving dietary recommendations and thereby achieving the best possible health outcomes through nutrition. In addition to macronutrient composition, the timing, frequency and number of meals may also play a significant role in the glycemic response to diet. Finally, socioeconomic, cultural and personal lifestyle factors also have an influence on the glycemic response. Therefore, this study aims to characterize the personal lifestyle differences between individuals with prediabetes, T2D, and those without prediabetes or T2D.
Furthermore, ketone bodies, specifically β-hydroxybutyrate (βHB), are gaining importance, as they serve as both metabolic biomarkers and alternative energy sources in periods of low carbohydrate availability. In individuals with insulin resistance or prediabetes, cerebral glucose utilization is often impaired, leading to the use of ketone bodies as a compensatory energy source for the brain. Findings indicate that the individual ketone response to dietary interventions varies significantly between individuals and could thus itself be relevant as a metabolic phenotype marker in the context of precision nutrition. Therefore, the study also aims to further investigate the extent to which exogenous βHB supplementation influences neurocognitive processes and decision-making behavior, and whether characteristic neurocognitive phenotypes can be derived from this in metabolic risk groups.
This study will achieve its aims by completing a comprehensive lifestyle characterization and metabolic, molecular and neurocognitive phenotyping of individuals with different glycemic status (prediabetes, type 2 diabetes [T2D], and absence of prediabetes or T2D) in a German cohort. The study consists of modules A and B. This record represents a description of module B; module A has an observational design and is registered as a separate record (NCT07868601).
Module A will include a 14-days observational period at home and two visits (screening and phenotyping visits) of the study center at the German Institute of Human Nutrition Potsdam-Rehbrücke before and after the observational period, respectively. Study visits of module A will include an intensive characterization of participants, comprising questionnaires, anthropometric and metabolic assessments, as well as the collection of biological samples. In the observation period, food intake, sleep, activity, and interstitial glucose will be monitored during 14 days, and test meals will be consumed at two days at specific times within this period.
Module B has an interventional crossover design and will take place 1-12 weeks after module A (or after the screening visit for participants not taking part in module A). It includes two visits of the study center at the Freie Universität Berlin, separated by a two-week interval. Study visits of module B will focus on neurocognitive phenotyping, comprising structural and functional magnetic resonance imaging (MRI) of the brain and computer-based decision-making tasks, performed after consumption of either a βHB-containing drink or an equicaloric and taste-matched carbohydrate (dextrose) drink, referred to as placebo drink in the following (test and placebo visits). Data from module A (registered separately [NCT07868601]; e.g., anthropometric and body composition data, blood parameters, CGM-derived glycemic parameters, gut microbiome, lifestyle, metabolic and questionnaire data) will be integrated with module B outcomes to examine associations between individual metabolic and lifestyle phenotypes and neurocognitive, behavioral, affective, physiological and metabolic measures, as well as responses to βHB supplementation. Participants who do not complete the measurements of module A will complete continuous glucose monitoring, actigraphy, sleep and dietary records and stool sample collection between the two module B visits. Module B outcomes will be analyzed with respect to drink condition (βHB vs. placebo), glycemic group, and their interaction.
The aims of the study are as follows:
Primary aims of the LIME study (addressed primarily in module A [NCT07868601], with contributions from module B):
- Identification of metabolic biomarkers and omics-based scores that predict individual glycemic response to food
- Identification of general lifestyle patterns that distinguish individuals with prediabetes or T2D from those without prediabetes or T2D, as well as individuals with prediabetes from those with T2D
- Identification of personal factors and differences in lifestyle patterns that predict individual glucose response to food
Primary aims (LIME-B study):
- Characterization of individual βHB and glucose responses to exogenous βHB supplementation and their association with glycemic status and individual metabolic and lifestyle phenotypes
- Investigation of the effects of exogenous βHB supplementation on neurocognitive processes, cognitive functioning as well as avoidance and decision-making behavior in individuals with different glycemic status
- Elucidation of neuronal, metabolic, and physiological mechanisms associated with specific lifestyle patterns
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Within-subject crossover design: each participant receives both the βHB drink and the placebo drink at two visits in module B, separated by an interval of approximately two weeks, in randomized order, stratified by glycemic group
| Arm | Type | Receives |
|---|---|---|
| βHB drink (ketone ester) | Experimental | Dietary Supplement: βHB drink (ketone ester)Participants receive a single dose of a βHB ester drink (0.3 g/kg body weight) at one of the two module B visits |
| Carbohydrate drink | Active comparator | Dietary Supplement: Carbohydrate drinkCarbohydrate drink Participants receive an equicaloric and taste-matched carbohydrate drink (placebo drink) at the other visit of module B |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Overweight or obese (BMI 25-40 kg/m²)
- Good knowledge of German
- Completion of the LIME screening visit; participants who do not take part in the further assessments of module A [NCT07868601] may still participate in module B
- Group A (without Prediabetes or Type 2 Diabetes) Criteria: HbA1c <5.7% and fasting plasma glucose < 100 mg/dl
- Group B (Prediabetes) Criteria: HbA1c 5.7-6.4%, or fasting plasma glucose 100-125 mg/dL
Key exclusion criteria (26 listed)
- Weight changes of more than 5% in the last 3 months
- Night shift work
- Travel across more than one time zone in the last month before and during study participation
- Intensive regular physical activity of more than 2 hours per day
- Current pregnancy or breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| βHB drink (ketone ester)Single oral dose of a βHB ester (0.3 g/kg body weight), consumed fasted during one of the two visits of module B | Dietary supplement | βHB drink (ketone ester) |
| Carbohydrate drinkSingle oral dose of an equicaloric and taste-matched dextrose drink. | Dietary supplement | Carbohydrate drink |
Primary outcome
βHB response to exogenous βHB supplementation
Time frame: 3-16 weeks
βHB area under the curve (AUC) from fasting and repeated postprandial blood samples after drink intake, compared between drink conditions (βHB vs. placebo) and glycemic groups
Time course of βHB concentrations
Time frame: 3-16 weeks
Fasting concentrations and time course of βHB concentrations at individual time points including derived metrics (e.g., peak concentration, time to peak, rate of change), compared between drink conditions (βHB vs. placebo) and glycemic groups
Fasting and postprandial glucose and insulin response
Time frame: 3-16 weeks
Fasting concentrations and postprandial time course of glucose, insulin and C-peptide in repeated blood samples after drink intake, including derived metrics (e.g., incremental area under the curve [iAUC], incremental peak, time to peak, amplitude, nadir, rate of change) and indices of insulin sensitivity (e.g., HOMA-IR), compared between drink conditions (βHB vs. placebo) and glycemic groups
Concentration of inflammatory markers
Time frame: 3-16 weeks
Interleukin-6 (IL-6) and hsCRP levels measured in fasting blood samples; IL-6 additionally in postprandial blood samples after drink intake, compared between drink conditions (βHB vs. placebo) and glycemic groups
Metabolic and stress-responsive hormones
Time frame: 3-16 weeks
Growth differentiation factor 15 (GDF15), fibroblast growth factor 21 (FGF21) and cortisol concentrations in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Gut and appetite-regulating hormones
Time frame: 3-16 weeks
Glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), ghrelin and leptin concentrations in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Lipolysis and energy metabolites
Time frame: 3-16 weeks
Free fatty acids, triglycerides, lactate and amino acids in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Oxidative stress markers
Time frame: 3-16 weeks
Oxidative stress markers such as Malondialdehyde and 3-Nitrotyrosine in fasting and postprandial blood samples, compared between drink conditions (βHB vs. placebo) and glycemic groups
Avoidance behavior
Time frame: 3-16 weeks
Time spent in less safe areas and exploratory movement in two virtual reality scenarios (elevated platform, dark maze), compared between drink conditions (βHB vs. placebo) and glycemic groups
Risky decision-making
Time frame: 3-16 weeks
Choice behavior in a lottery task during fMRI (e.g., proportion of risky choices, risk attitude), compared between drink conditions (βHB vs. placebo) and glycemic groups
Dual-task performance
Time frame: 3-16 weeks
Reaction times, accuracy and dual-task costs in an auditory-visual dual-task paradigm, compared between drink conditions (βHB vs. placebo) and glycemic groups
Heart rate and heart rate variability (HRV)
Time frame: 3-16 weeks
Heart rate and heart rate variability (HRV) from electrocardiography, compared between drink conditions (βHB vs. placebo) and glycemic groups
Skin conductance response
Time frame: 3-16 weeks
Electrodermal activity (EDA) measured via electrodermal activity electrodes, compared between drink conditions (βHB vs. placebo) and glycemic groups
Respiration rate
Time frame: 3-16 weeks
Task-based and resting-state respiration rate, measured via a respiration belt pulse (pulse oximetry during MRI), compared between drink conditions (βHB vs. placebo) and glycemic groups
Pulse
Time frame: 3-16 weeks
Pulse measured via pulse oximetry during MRI, compared between drink conditions (βHB vs. placebo) and glycemic groups
Gastric myoelectric activity
Time frame: 3-16 weeks
Gastric rhythm and power assessed by electrogastrography (EGG), compared between drink conditions (βHB vs. placebo) and glycemic groups
Brain Structure
Time frame: 3-16 weeks
Brain morphology (e.g., regional gray matter volume and density) assessed by T1-weighted structural MRI, compared between drink conditions (βHB vs. placebo) and glycemic groups
White matter micro- and macrostructure
Time frame: 3-16 weeks
White matter micro- and macrostructure assessed by diffusion-weighted imaging (DWI), compared between drink conditions (βHB vs. placebo) and glycemic groups
Resting-state functional connectivity
Time frame: 3-16 weeks
Functional connectivity between brain regions assessed by resting-state functional MRI (rs-fMRI), compared between drink conditions (βHB vs. placebo) and glycemic groups
Task-related brain activity
Time frame: 3-16 weeks
Brain activity during a risk-based decision-making task (lottery task) assessed by functional MRI (fMRI), compared between drink conditions (βHB vs. placebo) and glycemic groups
13 secondary outcomes
Module A phenotyping data as predictors, moderators and controls
Time frame: 2 weeks and 3-16 weeks
Body height
Time frame: 3-16 weeks
Body weight
Time frame: 3-16 weeks
Waist and hip circumference
Time frame: 3-16 weeks
Body Mass Index (BMI)
Time frame: 3-16 weeks
Subjective state during visits
Time frame: 3-16 weeks
Affective state
Time frame: 3-16 weeks
Anxiety
Time frame: 3-16 weeks
Perceived stress
Time frame: 3-16 weeks
Flow state
Time frame: 3-16 weeks
Food craving
Time frame: 3-16 weeks
Subjective hypoglycaemic symptoms
Time frame: 3-16 weeks
Other hormones and metabolites (exploratory)
Time frame: 3-16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Olga Ramich, Prof. Dr. principal investigator
German Institute of Human Nutrition Potsdam-Rehbrücke and the Charité - Universitätsmedizin Berlin
Soyoung Q Park, Prof. Dr. principal investigator
German Institute of Human Nutrition Potsdam-Rehbrücke and the Charité - Universitätsmedizin Berlin
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing βHB drink (ketone ester) and Carbohydrate drink in people with Nutritional and Metabolic Diseases and Prediabetes, run by German Institute of Human Nutrition at 2 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Soyoung Q Park, Prof. Dr. (+49 33200 882510, soyoung.park@dife.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
βHB response to exogenous βHB supplementation (time frame: 3-16 weeks). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.