Metabolic Flexibility to Predict Lifestyle Interventions Outcomes

NCT ID: NCT06329349

Last Updated: 2024-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-02

Study Completion Date

2026-04-01

Brief Summary

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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

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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

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Obesity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

2:1 randomized cross-over
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intervention

Exercise intervention

Group Type EXPERIMENTAL

Exercise

Intervention Type OTHER

12 weeks, 3 times a week of progressive endurance aerobic exercise (150 to 400kcal AEE per session)

Combined Exercise + Diet

Intervention Type OTHER

12 weeks, 25% caloric reduction, based on PMID: 37069434

Control

No intervention.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Exercise

12 weeks, 3 times a week of progressive endurance aerobic exercise (150 to 400kcal AEE per session)

Intervention Type OTHER

Combined Exercise + Diet

12 weeks, 25% caloric reduction, based on PMID: 37069434

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* BMI\>30
* age 25-45 years

Exclusion Criteria

* 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
Minimum Eligible Age

25 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Ministry of Health, Czech Republic

OTHER_GOV

Sponsor Role collaborator

EXCELES LX22NPO5104, CarDia

UNKNOWN

Sponsor Role collaborator

Charles University, Czech Republic

OTHER

Sponsor Role lead

Responsible Party

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Jan Gojda, MD

ass. prof. MD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jan Gojda

Role: PRINCIPAL_INVESTIGATOR

Third Faculty of Medicine Charles University

Locations

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University Hospital Kralovske Vinohrady

Prague, , Czechia

Site Status RECRUITING

Third Medical Faculty,Charles University

Prague, , Czechia

Site Status RECRUITING

Faculty of Sports Science

Prague, , Czechia

Site Status RECRUITING

Countries

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Czechia

Central Contacts

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Jan Gojda, PhD

Role: CONTACT

+420267163031

Jana Potočková

Role: CONTACT

+420267163031

Facility Contacts

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Jan Gojda, PhD

Role: primary

+420267163031

Katerina Koudelkova, MD

Role: backup

+420267163031

Michaela Šiklová, PhD

Role: primary

+420267102222

PhD

Role: backup

+420267163031

Michal Šteffl, PhD

Role: primary

+420220172072

Tomáš Větrovský, PhD

Role: backup

+420220172072

References

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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.

Reference Type DERIVED
PMID: 40340957 (View on PubMed)

Other Identifiers

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EK VP57/0/2023

Identifier Type: -

Identifier Source: org_study_id

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