ObesityMEPHISTONCT06329349
Metabolic Flexibility to Predict Lifestyle Interventions Outcomes
A study testing Exercise and Combined Exercise + Diet in people with Obesity, run by Charles University, Czech Republic at 3 sites in Czechia.
Trial summary
Weight loss is a cornerstone of diabetes (T2D) management, yet in clinical practice, its delivery is limited by its perceived burdensome nature and variability in response. Personalization of the interventions to increase their success rate is an unmet clinical need. Read more about this study
- Who is it for?
- Ages 25 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Exercise and Combined Exercise + Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesCzechia
- Study dates
- 2 Jan 2024to 1 Apr 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 25 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- BMI>30
- age 25-45 years
Who cannot join
- active cancer
- diabetes (medical history, fasting glycemia >7.6 and/or 2hOGTT glycemia >11.1)
- uncontrolled endocrine diseases
- corticosteroid therapy
- immune-suppressive therapy
- pregnancy
- breastfeeding
Trial locations and contacts
3 sites in 1 country.
Czechia3 sites, 3 recruiting
- Recruiting
University Hospital Kralovske Vinohrady
Prague, 10034
Jan Gojda, PhD, +420267163031, jan.gojda@lf3.cuni.cz
Katerina Koudelkova, MD, +420267163031, katerina.koudelkova@fnkv.cz
- Recruiting
Third Medical Faculty,Charles University
Prague, 10084
Michaela Šiklová, PhD, +420267102222, michaela.siklova@lf3.cuni.cz
PhD, +420267163031, jan.gojda@lf3.cuni.cz
- Recruiting
Faculty of Sports Science
Prague, 16000
Michal Šteffl, PhD, +420220172072, michal.steffl@ftvs.cuni.cz
Tomáš Větrovský, PhD, +420220172072, tomas.vetrovsky@ftvs.cuni.cz
About this study
Official title: Whole Body and Gut Microbiome Metabolic Flexibility to Predict Lifestyle Intervention Outcomes
Weight loss is a cornerstone of diabetes (T2D) management, yet in clinical practice, its delivery is limited by its perceived burdensome nature and variability in response. Personalization of the interventions to increase their success rate is an unmet clinical need. The proposed project MEPHISTO (Whole body and gut microbiome metabolic flexibility to predict lifestyle intervention outcomes) would aim to identify predictive features related to successful weight loss upon sequential exercise and diet intervention in people living with obesity. To this end, the study aims to conduct a clinical trial where the investigators would implement state-of-the-art physiological phenotyping of metabolic flexibility at the whole-body level and at the level of the gut in persons with obesity before and after exercise and diet + exercise intervention to identify predictive signatures of successful weight loss
Read the detailed description
Among the influential determinants impacting the efficacy and health outcomes of an intervention is an individual's level of metabolic flexibility (MetFlex). MetFlex denotes the body's capacity to adapt in response to alterations in metabolic demands and nutrient availability. Impaired MetFlex is evident in conditions such as obesity and diabetes, yet it may be ameliorated through lifestyle interventions such as exercise training or caloric restriction similar to improvements in insulin sensitivity. However, MetFlex has not been studied as a potential mechanism associated with successful weight loss. The decline in MetFlex, i.e. the limited cellular/tissue ability to manage excess or deficiency in energy substrates leads to compromised mitochondrial function and excessive lipid accumulation in ectopic tissues, resulting in metabolic disorders such as T2D or metabolic syndrome.
Another potential player predicting an individual's capacity to respond to lifestyle interventions is the gut microbiota (gut microbiome and metabolome, MIME). It was repeatedly shown to be among the most important sources of inter-individual variability when it comes to the development of obesity and responsiveness to dietary intervention The microbiome does not only influence host physiology directly, e.g. through contact with immune cells, but also through the vast array of metabolites produced, i.e. the microbiota-derived metabolome. The composition of the gut microbiota and the microbiota-derived metabolome is largely shaped by the host's diet, as this represents the main source of substances and energy for the microbiota. It is therefore striking that published studies to date have yielded rather inconsistent results regarding dietary interventions to alter gut microbiota composition. The discrepancy can be explained by the large variability of individual microbiomes at the beginning of the intervention, and similarly the baseline MIME signature significantly determines weight loss success.
Here the investigators present a complex project to investigate whether whole body and gut MetFlex can be further explored and used as ex-ante predictors of successful weight loss following exercise and dietary interventions, thus providing proof of concept and paving the way to personalized lifestyle interventions.
- Conditions
- Obesity
- Being tested
- Exercise, Combined Exercise + Diet
- Keywords
- obesity, metabolic flexibility, metabolomic, exercise, diet
- Medical subject headings
- Obesity, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExerciseOther
12 weeks, 3 times a week of progressive endurance aerobic exercise (150 to 400kcal AEE per session)
Combined Exercise + DietOther
12 weeks, 25% caloric reduction, based on PMID: 37069434
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Exercise intervention Receives: Other: Exercise; Other: Combined Exercise + Diet |
| Control | No intervention | No intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in metabolic flexibility (MetFlex (ΔRQ 200-0))
change in metabolic flexibility measured as ΔRQ (respiratory quotient) during glucose clamp
Measured: 18 months
Change in insulin sensitivity
change in insulin sensitivity measured as glucose infusion rate (GIR) during glucose clamp
Measured: 18 months
Secondary outcomes (3)
Glucose tolerance relate to primary outcomes changes
fasting/2h oral glucose tolerance test glycemia positively relate to weight loss.
Measured: 18 months
HbA1c relate to primary outcomes changes
HbA1c positively relate to weight loss.
Measured: 18 months
Insulin sensitivity relate to primary outcomes changes
GIR positively relate to weight loss.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2024
- Study start2 Jan 2024
- Primary completion12 Dec 2025 (estimated)
- Study completion1 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Charles University, Czech RepublicThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2:1 randomized cross-over
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Charles University, Czech Republic
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, Czech Republic, EXCELES LX22NPO5104, CarDia
- Responsible party
- Principal investigator, Jan Gojda, MD, Charles University, Czech Republic
- Investigators
- Jan Gojda, Principal investigator, Charles University, Czech Republic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06329349
- Sponsor's protocol ID
- EK VP57/0/2023
- Acronym
- MEPHISTO
- Status last verified
- Aug 2024
- First submitted
- 1 Mar 2024
- Last updated
- 28 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: After anonymization, the data would be shared upon reasonable request.
Publications
Ludlova M, Koudelkova K, Pallova J, Koudelkova B, Siklova M, Cahova M, Vetrovsky T, Steffl M, Gojda J. Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial. JMIR Res Protoc. 2025 May 8;14:e67570. doi: 10.2196/67570.
PubMed 40340957
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Whole Body and Gut Microbiome Metabolic Flexibility to Predict Lifestyle Intervention Outcomes
- ClinicalTrials.gov ID
- NCT06329349
- Acronym / sponsor ID
- MEPHISTO / EK VP57/0/2023
- Conditions
- Obesity
- Keywords
- obesity, metabolic flexibility, metabolomic, exercise, diet
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Charles University, Czech RepublicUniversity, hospital or other
- Collaborators
- Ministry of Health, Czech Republic, EXCELES LX22NPO5104, CarDia
- Study start
- 2 Jan 2024 (actual)
- Primary completion
- 12 Dec 2025 (estimated)
- Study completion
- 1 Apr 2026 (estimated)
- First posted
- 25 Mar 2024 (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.
Weight loss is a cornerstone of diabetes (T2D) management, yet in clinical practice, its delivery is limited by its perceived burdensome nature and variability in response. Personalization of the interventions to increase their success rate is an unmet clinical need. The proposed project MEPHISTO (Whole body and gut microbiome metabolic flexibility to predict lifestyle intervention outcomes) would aim to identify predictive features related to successful weight loss upon sequential exercise and diet intervention in people living with obesity. To this end, the study aims to conduct a clinical trial where the investigators would implement state-of-the-art physiological phenotyping of metabolic flexibility at the whole-body level and at the level of the gut in persons with obesity before and after exercise and diet + exercise intervention to identify predictive signatures of successful weight loss
Detailed description
Among the influential determinants impacting the efficacy and health outcomes of an intervention is an individual's level of metabolic flexibility (MetFlex). MetFlex denotes the body's capacity to adapt in response to alterations in metabolic demands and nutrient availability. Impaired MetFlex is evident in conditions such as obesity and diabetes, yet it may be ameliorated through lifestyle interventions such as exercise training or caloric restriction similar to improvements in insulin sensitivity. However, MetFlex has not been studied as a potential mechanism associated with successful weight loss. The decline in MetFlex, i.e. the limited cellular/tissue ability to manage excess or deficiency in energy substrates leads to compromised mitochondrial function and excessive lipid accumulation in ectopic tissues, resulting in metabolic disorders such as T2D or metabolic syndrome.
Another potential player predicting an individual's capacity to respond to lifestyle interventions is the gut microbiota (gut microbiome and metabolome, MIME). It was repeatedly shown to be among the most important sources of inter-individual variability when it comes to the development of obesity and responsiveness to dietary intervention The microbiome does not only influence host physiology directly, e.g. through contact with immune cells, but also through the vast array of metabolites produced, i.e. the microbiota-derived metabolome. The composition of the gut microbiota and the microbiota-derived metabolome is largely shaped by the host's diet, as this represents the main source of substances and energy for the microbiota. It is therefore striking that published studies to date have yielded rather inconsistent results regarding dietary interventions to alter gut microbiota composition. The discrepancy can be explained by the large variability of individual microbiomes at the beginning of the intervention, and similarly the baseline MIME signature significantly determines weight loss success.
Here the investigators present a complex project to investigate whether whole body and gut MetFlex can be further explored and used as ex-ante predictors of successful weight loss following exercise and dietary interventions, thus providing proof of concept and paving the way to personalized lifestyle interventions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 2:1 randomized cross-over
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Exercise, Other: Combined Exercise + DietExercise intervention |
| Control | No intervention | –No intervention. |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- BMI>30
- age 25-45 years
Key exclusion criteria (7 listed)
- active cancer
- diabetes (medical history, fasting glycemia >7.6 and/or 2hOGTT glycemia >11.1)
- uncontrolled endocrine diseases
- corticosteroid therapy
- immune-suppressive therapy
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 |
|---|---|---|
| Exercise12 weeks, 3 times a week of progressive endurance aerobic exercise (150 to 400kcal AEE per session) | Other | Intervention |
| Combined Exercise + Diet12 weeks, 25% caloric reduction, based on PMID: 37069434 | Other | Intervention |
Primary outcome
Change in metabolic flexibility (MetFlex (ΔRQ 200-0))
Time frame: 18 months
change in metabolic flexibility measured as ΔRQ (respiratory quotient) during glucose clamp
Change in insulin sensitivity
Time frame: 18 months
change in insulin sensitivity measured as glucose infusion rate (GIR) during glucose clamp
3 secondary outcomes
Glucose tolerance relate to primary outcomes changes
Time frame: 18 months
HbA1c relate to primary outcomes changes
Time frame: 18 months
Insulin sensitivity relate to primary outcomes changes
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Derived from this study: PubMed 40340957Ludlova M, Koudelkova K, Pallova J, Koudelkova B, Siklova M, Cahova M, Vetrovsky T, Steffl M, Gojda J. Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial. JMIR Res Protoc. 2025 May 8;14:e67570. doi: 10.2196/67570.
- Individual participant dataSharing planned: No. After anonymization, the data would be shared upon reasonable request.
Related trials for Obesity
Recruiting
Preserving Muscle Mass During Incretin-Induced Weight Loss
Obesity (BMI > 35)
Not yet recruitingObservational study
A Natural History of Genetic and Environmental Predictors of Pubertal Timing Among Youth With Obesity
Obesity
Not yet recruitingObservational study
Assessing the Impact of Perceptions of Unpredictability on Objective Measures of Food Consumption and Metabolism
Healthy Volunteer, Obestity
Not yet recruitingPhase 2
Trial of the Combination of Alpha-Lipoic Acid and Mirabegron in Women and in Men With Obesity
Insulin Resistance, Obesity
Recruiting
Synchronous vs Asynchronous Remotely Delivered Lifestyle Interventions
Obesity
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. This study is not recruiting at the moment.
Jan Gojda principal investigator
Charles University, Czech Republic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise and Combined Exercise + Diet in people with Obesity, run by Charles University, Czech Republic at 3 sites in Czechia.
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 2 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Czechia. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jan Gojda, PhD (+420267163031, jan.gojda@lf3.cuni.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in metabolic flexibility (MetFlex (ΔRQ 200-0)) (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06329349, which also lists 1 linked publication.
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 28 Aug 2024.