Proof of Concept in the Prevention of Post-bariatric Sarcopenia: Simulated Activation of the "Gravitostat"

Official title

Proof of Concept in the Prevention of Post-bariatric Sarcopenia: Simulated Activation of the "Gravitostat", Randomized Pilot Study

Overview

Due to its mechanical and metabolic functions, muscle loss leads to resistance to weight loss during caloric restriction, particularly in patients with obesity. The recent discovery of a "gravitational" homeostatic system, induced by an additional load to body weight, suggests the existence of a new weight control mechanism. Such a "gravitostat" would ensure a form of weight homeostasis mediated by afferent signals originating from osteocytes in response to gravity perception. This hypothesis, initially derived from animal studies, has more recently been tested in humans. It shows that "activation of the gravitostat" through artificial increases in body weight facilitates body weight reduction without affecting lean mass (LM). Therefore, this "gravitostat" could contribute to preserving LM despite the loss of fat mass , whereas its decline may compromise muscle mass and function after bariatric surgery, despite undeniable improvements in comorbidities. The present study aims to reduce the "metabolic load" (i.e., decreasing insulin resistance and inflammation) to promote muscle protein anabolism, while maintaining the "mechanical load" (by preserving initial body weight during weight loss induced by bariatric surgery) in order to activate the "gravitostat" and preserve muscle mass and function. Currently, there are no clear recommendations or strategies to prevent muscle loss in patients who have undergone bariatric surgery. This simple concept, applied during drastic muscle loss, should help improve muscle health.

Interventions

• Other maintaining mechanical load
  The method for maintaining mechanical load (artificially reproducing the stabilization of initial body weight) will involve the use of a weighted vest. Participants will be asked to wear the weighted vest for at least eight hours a day over a four-week period without changing their lifestyle. Patients will also be contacted by phone every week after surgery to confirm that they are using the vest in accordance with the protocol and to collect information on any potential adverse events. During

Primary outcome measures

• Loss of lean mass at 1 monts and 3 months after bariatric surgery in patients undergoing "weight compensation" compared to a group of patients following a conventional approach (without gravitostat activation). [Time frame: 1 month and 3 months after bariatric surgery]

Secondary outcome measures (12)

• Loss of lean mass at 6 months after bariatric surgery in patients undergoing "weight compensation" compared to a group of patients following a conventional approach (without gravitostat activation). [Time frame: 6 months after bariatric surgery]
• Change from baseline on weight at 1 month (M1), 3 months (M3), and 6 months (M6) [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Change from baseline on BMI at 1 month (M1), 3 months (M3), and 6 months (M6) [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Change from baseline on waist circumference at 1 month (M1), 3 months (M3), and 6 months (M6) [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Change from baseline on hip circumference at 1 month (M1), 3 months (M3), and 6 months (M6) [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Muscle mass in the arms and legs at 1 month (M1), 3 months (M3), and 6 months (M6) after surgery [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Changes in muscle function (Handgrip strength test) at 1 month (M1), 3 months (M3), and 6 months (M6) after surgery [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Changes in muscle function (Short Physical Performance Battery (SPPB)) at 1 month (M1), 3 months (M3), and 6 months (M6) after surgery [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Changes in muscle function (6-minute walk test (TM6)) at 1 month (M1), 3 months (M3), and 6 months (M6) after surgery [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Changes from baseline on muscle architechture at 1 month (M1), 3 months (M3), and 6 months (M6) after surgery [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Changes from baseline on bone architechture at 1 month (M1), 3 months (M3), and 6 months (M6) after surgery [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]
• Changes from baseline on bone architecture at 1 month (M1), 3 months (M3), and 6 months (M6) after surgery [Time frame: 1 month (M1), 3 months (M3), and 6 months (M6)]

Eligibility criteria

Inclusion criteria

• Female participants
• Aged between 18 and 60 years
• Planned for bariatric surgery, such as sleeve gastrectomy
• Able to give informed consent to participate in research
• Affiliated to a social security scheme

Exclusion criteria

• Women weighing 170 kg or more
• Inability to move around independently.
• Participants with a spinal pathology.
• Pregnant or breast-feeding women.
• Inability to comply with protocol recommendations.
• Adults under legal guardianship (curatorship, guardianship, deprivation of liberty, patients benefiting from a judicial protection measure or safeguard of justice).
• Refusal to participate.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

France · 1 center

• CHU Clermont-Ferrand — Clermont-Ferrand

Publications

• Ciangura C, Bouillot JL, Lloret-Linares C, Poitou C, Veyrie N, Basdevant A, Oppert JM. Dynamics of change in total and regional body composition after gastric bypass in obese patients. Obesity (Silver Spring). 2010 Apr;18(4):760-5. doi: 10.1038/oby.2009.348. Epub 2009 Oct 15. PMID 19834464
• Thivel D, Boirie Y. The Gravitostat theory: Body fat is lost but is fat-free mass preserved? EClinicalMedicine. 2020 Oct 3;27:100531. doi: 10.1016/j.eclinm.2020.100531. eCollection 2020 Oct. No abstract available. PMID 33033796
• Ohlsson C, Hagg DA, Hammarhjelm F, Dalmau Gasull A, Bellman J, Windahl SH, Palsdottir V, Jansson JO. The Gravitostat Regulates Fat Mass in Obese Male Mice While Leptin Regulates Fat Mass in Lean Male Mice. Endocrinology. 2018 Jul 1;159(7):2676-2682. doi: 10.1210/en.2018-00307. PMID 29800288
• Jansson JO, Palsdottir V, Hagg DA, Schele E, Dickson SL, Anesten F, Bake T, Montelius M, Bellman J, Johansson ME, Cone RD, Drucker DJ, Wu J, Aleksic B, Tornqvist AE, Sjogren K, Gustafsson JA, Windahl SH, Ohlsson C. Body weight homeostat that regulates fat mass independently of leptin in rats and mice. Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):427-432. doi: 10.1073/pnas.1715687114. Epub 2017 Dec PMID 29279372

Identifiers

NCT: NCT07120685 · AOI 2023 BOIRIE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗