Bone Marrow Adipose Tissue in Relation to Bone and Energy Metabolism in Obesity and Type 2 Diabetes Mellitus

NCT07731438 | Recruiting

• 1 other identifier: NU23-01 00125
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

This interventional study is part of a broader research project entitled "Bone Marrow Adipose Tissue in Relation to Bone and Energy Metabolism in Obesity and Type 2 Diabetes Mellitus." The broader project includes both a cross-sectional study evaluating bone marrow adipose tissue and bone marrow mesenchymal stem cells in people with different metabolic and bone disorders and the present dietary intervention study. The interventional study investigates whether caloric restriction changes bone marrow adipose tissue, bone health, whole-body metabolism, and the molecular and cellular characteristics of bone marrow mesenchymal stem cells in obese non-diabetic premenopausal women. A group of lean healthy premenopausal women will serve as a comparison group. Participants in the intervention group will undergo an eight-week formula-based very-low-calorie diet using Cambridge Weight Plan products, providing approximately 2.5-3.35 MJ (600-800 kcal) per day, followed by a dietary weight-maintenance phase. Participants will receive nutritional counselling, and dietary adherence, body weight, physical activity, and clinical status will be monitored during scheduled study visits. Clinical and laboratory assessments will be conducted at baseline and after 2, 6, and 12 months. Assessments will include magnetic resonance imaging and proton magnetic resonance spectroscopy of the lumbar spine to measure the amount and lipid composition of vertebral bone marrow adipose tissue. Bone mineral density and body composition will be measured using dual-energy X-ray absorptiometry, with particular attention to bone mineral density at the total hip and femoral neck. Additional measurements will include body weight, waist and hip circumference, body composition, physical activity, and fasting blood tests evaluating bone turnover, glucose and lipid metabolism, inflammatory markers, hormones, and adipokines. Bone marrow aspirates and abdominal subcutaneous adipose tissue biopsies will be obtained at baseline and after six months. Bone marrow-derived and adipose tissue-derived mesenchymal stem cells will be examined for changes in cellular composition, gene-expression profiles, metabolic activity, oxidative stress, differentiation capacity, and senescence-related characteristics. Single-cell RNA sequencing will be used to characterize specific bone marrow mesenchymal stem cell subpopulations. Bone marrow plasma and other biological samples will also undergo metabolomic, lipidomic, and proteomic profiling using high-resolution mass spectrometry. These analyses will be used to identify extracellular molecules and molecular patterns associated with glucose and lipid metabolism, inflammation, cellular senescence, and the response to caloric restriction. The study aims to determine whether diet-induced weight loss can improve the bone marrow microenvironment and modify vertebral bone marrow fat, bone parameters, and the metabolic and senescent phenotype of mesenchymal stem cells. The findings may help identify imaging, cellular, and molecular markers of obesity-related bone fragility.

Conditions

Obesity

Keywords

Bone marrow adipose tissue; Obesity; Caloric Restriction; Energy Metabolism; Magnetic Resonance imaging; Proton Magnetic Resonance Spectroscopy; Bone marrow mesenchymal stem cells; Bone metabolism; Cellular senescence; Single-cell RNA sequencing; Diet-induced weight loss

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Mean L2-L4 Vertebral Bone Marrow Adipose Tissue Proton Density Fat Fraction

  Vertebral bone marrow adipose tissue proton density fat fraction will be measured in the L2, L3, and L4 vertebral bodies using the mDIXON Quant MRI sequence. The mean value across the three vertebral bodies will be reported as a percentage.

  Baseline, Week 24, and Week 48

• Change From Baseline in Mean L2-L4 Vertebral Bone Marrow Adipose Tissue Unsaturation Index

  The lipid composition of vertebral bone marrow adipose tissue will be measured in the L2, L3, and L4 vertebral bodies using proton magnetic resonance spectroscopy. A prespecified unsaturation index will be calculated from the unsaturated and total lipid signals. The mean value across the three vertebral bodies will be reported.

  Baseline, Week 24, and Week 48

• Change from baseline in BM-MSC and AT-MSC potency, differentiation, senescence, and metabolic adaptation

  Change from baseline to Week 24 in characteristics of bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs). Potency is assessed using the colony-forming unit-fibroblast (CFU-F) assay and proliferation rate. Osteogenic differentiation is assessed by alkaline phosphatase (ALP) activity and expression of ALPL and RUNX2; adipogenic differentiation is assessed by Nile Red staining and expression of ADIPOQ and LEP. Senescence is assessed by senescence-associated β-galactosidase activity and expression of p16INK4a and p21. Metabolic adaptation is assessed by extracellular flux analysis of mitochondrial respiration and glycolytic capacity and by insulin-signaling activation. For each parameter, the outcome is the change from baseline to Week 24, compared between BM-MSCs and AT-MSCs.

  Baseline and Week 24

Secondary Outcomes (4)

• Change from baseline in metabolomic and lipidomic profile of bone marrow and plasma

  Baseline and Week 24

• Change From Baseline in Total Hip Bone Mineral Density

  Baseline, Week 24, and Week 48

• Change From Baseline in Lumbar Spine Bone Mineral Density

  Baseline, Week 24, and Week 48

• Change From Baseline in Femoral Neck Bone Mineral Density

  Baseline, Week 24, and Week 48

Other Outcomes (3)

• Change From Baseline in the Abdominal Subcutaneous-to-Visceral Adipose Tissue Ratio

  Baseline, Week 24, and Week 48

• Change From Baseline in Total Body Fat Mass Measured by DXA

  Baseline, Week 24, and Week 48

• Change From Baseline in Bone-Free Lean Mass Measured by DXA

  Baseline, Week 24, and Week 48

Study Arms (2)

Caloric Restriction Group

EXPERIMENTAL

Obese non-diabetic premenopausal women and age-eligible men will undergo an eight-week very-low-calorie formula diet followed by a weight-maintenance phase. Participants will receive nutritional counseling and undergo longitudinal clinical, anthropometric, biochemical, imaging, and cellular assessments to evaluate changes in vertebral bone marrow adipose tissue, bone mineral density, body composition, metabolic parameters, and the phenotype of bone marrow- and adipose tissue-derived mesenchymal stromal cells.

Behavioral: Caloric Restriction

Lean Healthy Baseline Reference Group

NO INTERVENTION

Lean healthy premenopausal women or age-eligible men will serve as a baseline reference group. Participants in this arm will not receive caloric restriction or any other study intervention and will not undergo longitudinal follow-up. Baseline assessments include clinical and anthropometric evaluation, blood sampling, bone mineral density and body composition measurements, magnetic resonance imaging and proton magnetic resonance spectroscopy of the lumbar spine, and collection of bone marrow and subcutaneous adipose tissue samples. Their baseline findings will be compared with those of participants with obesity.

Interventions

Caloric Restriction BEHAVIORAL

Participants will follow a formula-based very-low-calorie diet (Cambridge Weight Plan) providing approximately 600-800 kcal per day (2.5-3.35 MJ per day) for 8 weeks. This will be followed by a 4-month low-calorie diet phase and subsequently by a weight-maintenance phase. Participants will receive nutritional counselling, and dietary adherence, body weight, physical activity, and clinical status will be monitored during scheduled study visits.

Caloric Restriction Group

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Premenopausal women and age-eligible men assigned to either the obese intervention group or the lean control group
• Obese intervention group:
• Body mass index (BMI) of 30-42 kg/m²
• Fasting plasma glucose less than 6.4 mmol/L
• Age 25-55 years
• Lean control group:
• BMI of 19-25 kg/m²
• Fasting plasma glucose less than 6.4 mmol/L
• Age 25-50 years

You may not qualify if:

• Diabetes mellitus
• Secondary osteoporosis
• History of severe neuropathic disease
• Hyperparathyroidism
• Hyperthyroidism
• Immobilization
• Alcoholism
• Chronic gastrointestinal disease
• Significant chronic renal impairment, including any of the following:
• Chronic kidney disease
• Serum creatinine greater than 110 µmol/L
• Estimated glomerular filtration rate (eGFR) less than 1 mL/s/1.73 m²
• Proteinuria
• Diabetic nephropathy
• Chronic hepatic impairment

Sponsors & Collaborators

• General University Hospital, Prague: lead
• Czech Academy of Sciences: collaborator
• Ministry of Health, Czech Republic: collaborator

Study Sites (3)

General University Hospital in Prague

Prague, 12800, Czechia

RECRUITING

Institute of Endocrinology, Prague, a state-funded organization established by the Ministry of Health of the Czech Republic.

Prague, 12800, Czechia

RECRUITING

Institute of Physiology of the Czech Academy of Sciences

Prague, 14200, Czechia

RECRUITING

Related Publications (1)

• Tencerova M, Frost M, Figeac F, Nielsen TK, Ali D, Lauterlein JL, Andersen TL, Haakonsson AK, Rauch A, Madsen JS, Ejersted C, Hojlund K, Kassem M. Obesity-Associated Hypermetabolism and Accelerated Senescence of Bone Marrow Stromal Stem Cells Suggest a Potential Mechanism for Bone Fragility. Cell Rep. 2019 May 14;27(7):2050-2062.e6. doi: 10.1016/j.celrep.2019.04.066.

  PMID: 31091445 BACKGROUND

MeSH Terms

Conditions

Obesity

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Michaela Tencerova, MSc, PhD

  Institute of Physiology of the Czech Academy of Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vit Zikan, MD, Ph.D.

CONTACT

+420731670425; vit.zikan@vfn.cz

Michaela Tencerova, M.Sc., Ph.D.

CONTACT

+420 241 062737; michaela.tencerova@fgu.cas.cz

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Metabolic Bone Centre and Principal Investigator

Model Details: This is a non-randomized, parallel-group study. Obese non-diabetic premenopausal women age-eligible men undergo an eight-week very low-calorie dietary intervention followed by a weight-maintenance phase. Lean healthy premenopausal women and age-eligible men serve as a non-interventional reference group and are assessed at baseline only, without longitudinal follow-up.

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 28, 2026
• Study Start: May 1, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): January 21, 2027
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: De-identified individual participant data and supporting information will be available beginning 6 months after publication of the primary study results and will remain available for 5 years after publication.
• Access Criteria: Qualified researchers with a scientifically sound proposal will be able to access de-identified individual participant data underlying the published results, together with the study protocol and statistical analysis plan. Access will be granted following review and approval by the principal investigator and relevant institutional authorities, subject to a data-use agreement and applicable ethical and data-protection requirements. Requests should be submitted to the principal investigator, and approved data will be provided through a secure data-transfer method.

Locations

CZ (3)