Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial
BackgroundWeight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is...
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JMIR Publications
2025-05-01
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| Series: | JMIR Research Protocols |
| Online Access: | https://www.researchprotocols.org/2025/1/e67570 |
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| author | Monika Ludlova Kateřina Koudelková Jitka Pallova Barbora Koudelkova Michaela Siklova Monika Cahova Tomas Vetrovsky Michal Steffl Jan Gojda |
| author_facet | Monika Ludlova Kateřina Koudelková Jitka Pallova Barbora Koudelkova Michaela Siklova Monika Cahova Tomas Vetrovsky Michal Steffl Jan Gojda |
| author_sort | Monika Ludlova |
| collection | DOAJ |
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BackgroundWeight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need.
ObjectiveIdentification of predictive factors associated with successful weight loss after sequential exercise in women with obesity.
MethodsThe study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures.
ResultsRecruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026.
ConclusionsThis intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions.
Trial RegistrationClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349
International Registered Report Identifier (IRRID)DERR1-10.2196/67570 |
| format | Article |
| id | doaj-art-008be2079a98431ba4cf41d7bcfb28d8 |
| institution | DOAJ |
| issn | 1929-0748 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | JMIR Publications |
| record_format | Article |
| series | JMIR Research Protocols |
| spelling | doaj-art-008be2079a98431ba4cf41d7bcfb28d82025-08-20T03:09:24ZengJMIR PublicationsJMIR Research Protocols1929-07482025-05-0114e6757010.2196/67570Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled TrialMonika Ludlovahttps://orcid.org/0009-0008-6796-4847Kateřina Koudelkováhttps://orcid.org/0000-0003-2053-9698Jitka Pallovahttps://orcid.org/0009-0002-2971-1845Barbora Koudelkovahttps://orcid.org/0009-0006-1027-8518Michaela Siklovahttps://orcid.org/0000-0003-0489-1069Monika Cahovahttps://orcid.org/0000-0003-2640-5084Tomas Vetrovskyhttps://orcid.org/0000-0003-2529-7069Michal Stefflhttps://orcid.org/0000-0001-7297-8145Jan Gojdahttps://orcid.org/0000-0002-7995-5947 BackgroundWeight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need. ObjectiveIdentification of predictive factors associated with successful weight loss after sequential exercise in women with obesity. MethodsThe study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures. ResultsRecruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026. ConclusionsThis intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions. Trial RegistrationClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349 International Registered Report Identifier (IRRID)DERR1-10.2196/67570https://www.researchprotocols.org/2025/1/e67570 |
| spellingShingle | Monika Ludlova Kateřina Koudelková Jitka Pallova Barbora Koudelkova Michaela Siklova Monika Cahova Tomas Vetrovsky Michal Steffl Jan Gojda Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial JMIR Research Protocols |
| title | Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial |
| title_full | Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial |
| title_fullStr | Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial |
| title_full_unstemmed | Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial |
| title_short | Metabolic Flexibility to Predict Lifestyle Interventions Outcomes (MEPHISTO): Protocol for Predictive Validation Study and Randomized Controlled Trial |
| title_sort | metabolic flexibility to predict lifestyle interventions outcomes mephisto protocol for predictive validation study and randomized controlled trial |
| url | https://www.researchprotocols.org/2025/1/e67570 |
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