Energy Expenditure and Neuromuscular Function in Young Adult Women With a Naturally Thin Build (LeanErgy)

Centre Hospitalier Emile Roux

Status: Not yet enrolling

Conditions: Constitutional Thinness

Treatments: Diagnostic Test: Evaluation of the energy cost of walking; Diagnostic Test: Neuro-muscular assessments; Diagnostic Test: Evaluation of the maximum oxidation point of lipids

Study type: Interventional

Funder types: Other

Identifiers

NCT07233109

2025-A01848-41 (Other Identifier)

RIPH2_GADEA_LeanErgy

Details and patient eligibility

About

People with a low BMI (<17.5) are most often considered to have anorexia nervosa (AN). However, recent literature suggests that there is a category of individuals with the same low BMI who do not meet the diagnostic criteria for anorexia nervosa but who have specific differences that make them a separate entity: constitutional thinness (CM). Constitutional thinness differs from anorexia nervosa in several ways. First, unlike AN, CM individuals do not have eating disorders and express a strong desire to gain weight. Another difference concerns the menstrual cycle: without oral contraception, AN individuals experience amenorrhea, while CM individuals have regular menstrual cycles. Biological signs of malnutrition are also present in anorexia nervosa, whereas this is not the case in constitutional thinness. Indeed, concentrations of IGF1, free T3, and leptin are significantly reduced in AN compared to healthy subjects, whereas there is no significant difference between healthy subjects and CT. Finally, in terms of body composition, there is a significant difference in particular in the percentage of fat mass between MC and AM subjects, with the MC group having a significantly lower percentage of fat mass than the control subjects but significantly higher than the AM subjects. The clinical management of MC patients could involve nutritional management of patients but also management in the form of an Adapted Physical Activity intervention program. However, this type of program using physical activity and a nutritional approach must be based on a characterization of the energy profile and physical abilities of MC patients, which remains to be studied. Germain et al. proposed measuring the physical activity level of MC patients using Actiheart (a combination of heart rate and accelerometer) and compared it with that of normal-weight (NW) individuals, finding no difference between the groups. However, this analysis remains a secondary analysis of their study, as the statistical power and choice of tool are certainly not appropriate for this question. Our team recently conducted the Nutrilean project, which for the first time questioned the aerobic and muscular capacities of women with CM compared to their NP counterparts. While our results show lower force production capacity in CM patients, suggesting neuromuscular adaptations to the chronic mechanical unloading caused by CM rather than an impairment of contractile abilities themselves, this remains to be explored more specifically. Indeed, these differences disappeared after normalization to body weight or muscle mass, suggesting a reduced gross force production capacity, but probably reflecting a normal physiological adaptation to low body and muscle mass. It now appears necessary to carry out more specific neuromuscular analyses in order to better understand the mechanisms, adaptations, and/or potential neuromuscular dysfunctions in this population. Similarly, while the results do not appear to show any impairment in the aerobic capacity of CM, they do highlight a potential impairment in their energy efficiency during locomotion, which may also reflect an adaptation to chronic exposure to lower mechanical loads.

In this context and following on from the work carried out to date by our team, the main objective of this study is i) to compare the lipid oxidation capacity and energy cost of walking between MC and NP participants; ii) to explore the adaptations of this energy cost in MC women in response to mechanical overload.

Enrollment: 36 estimated patients

Sex: Female

Ages: 18 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• BMI ≤ 17.5 kg/m2
• 20 kg/m2 ≤ BMI ≤ 25 kg/m2

Exclusion criteria

• For women with Constitutional thinness :

  • Women under guardianship or deprived of their liberty by judicial or administrative decision
  • Women who are pregnant, breastfeeding, or likely to become pregnant
  • Women who engage in intense physical activity (more than 3 sessions of physical activity per week)
  • Abnormal levels of IGF-1, estradiol, free T3, cortisol, and leptin
  • For the MC group specifically: cases of thinness due to a suspected organic cause. This includes Marfan syndrome, identifiable by: personal or family history of degenerative aortic disease (aneurysm, dissection), ligamentous hyperlaxity, arachnodactyly
  • History or presence of a systemic condition likely to interfere with the physiological and metabolic parameters measured (e.g., diabetes, endocrine or metabolic disease)
  • Any acute or chronic disease that may influence the results (e.g., infections, tumors, inflammatory diseases)
  • Medical or surgical history deemed by the investigator to be incompatible with this study (e.g., muscular, neurological, or joint disorders, or contraindications to the application of a magnetic field, etc.) Presence of diabetes, and any other condition limiting the application of either strategy under trial
  • Use of medications that may interfere with the study results
  • Cardiovascular conditions (history of cardiovascular and/or neurovascular disease, as well as the presence of cardiovascular and/or neurovascular risk factors other than obesity/overweight, such as: high blood pressure, high cholesterol, diabetes, heart rhythm disorder, known carotid atherosclerosis, thrombophilia)
  • Surgery within the previous 3 months
  • Women excluded from another study
  • Regular tobacco or alcohol consumption
  • Specific diets likely to impact metabolism, influence biological parameters (FT3, cortisol in particular) or skew results (deficiencies, low calorie intake). This includes vegan, mono, ketogenic, and low-calorie diets, intermittent fasting, or diets requiring specific supplementation that may interfere with the endocrine system.

For women Normal-Weighted Women

• Women under guardianship or deprived of their liberty by judicial or administrative decision
• Women who are pregnant, breastfeeding, or likely to become pregnant.
• Women who engage in intense physical activity (more than 3 sessions of physical activity per week)
• History or presence of a systemic condition likely to interfere with the physiological and metabolic parameters measured (e.g., diabetes, endocrine or metabolic disorders)
• Any acute or chronic disease that may influence the results (e.g., infections, tumors, inflammatory diseases)
• Medical or surgical history deemed by the investigator to be incompatible with this study (e.g., muscular, neurological, or joint disorders, or contraindications to the application of a magnetic field, etc.)
• Presence of diabetes or any other condition limiting the application of either strategy under investigation
• Taking medications that may interfere with the study results
• Cardiovascular conditions (history of cardiovascular and/or neurovascular disease, as well as the presence of cardiovascular and/or neurovascular risk factors other than obesity/overweight, such as: high blood pressure, high cholesterol, diabetes, heart rhythm disorder, known carotid atherosclerosis, thrombophilia)
• Surgery within the previous 3 months
• Women excluded from another study
• Regular tobacco or alcohol consumption
• Specific diets likely to impact metabolism, influence biological parameters, or skew results (deficiencies, low calorie intake). This includes vegan, mono, ketogenic, and low-calorie diets, intermittent fasting, or diets requiring specific supplementation that may interfere with the endocrine system.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 2 patient groups

Woman with constitutional thinness

Experimental group

Description:

Women aged between 18 and 35 Signed consent form Member of or entitled to social security Body Mass Index ≤ 17.5 kg/m2 Stable weight (no variation of more than 2kg over the last 12 months) No eating disorders No signs of malnutrition according to blood tests for cortisol\* and FT3\* No secondary amenorrhea

Treatment:

Diagnostic Test: Evaluation of the maximum oxidation point of lipids

Diagnostic Test: Neuro-muscular assessments

Diagnostic Test: Evaluation of the energy cost of walking

Normal-weight women

Experimental group

Description:

Women aged between 18 and 35 Signed consent form Member of or entitled to social security Body Mass Index between 20 kg/m² and 25 kg/m² Stable weight (No variation of more than 2 kg over the last 12 months) No eating disorders No secondary amenorrhea

Treatment:

Diagnostic Test: Evaluation of the maximum oxidation point of lipids

Diagnostic Test: Neuro-muscular assessments

Diagnostic Test: Evaluation of the energy cost of walking