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

ClinicalTrials.gov IDNCT07731438

PhaseNA

Enrollment45

SponsorGeneral University Hospital, Prague

Age21 Years – 55 Years

SexALL

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Conditions studied

Obesity

About this study

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…

Interventions

Behavioral: Caloric Restriction — 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.

Primary outcomes

Change From Baseline in Mean L2-L4 Vertebral Bone Marrow Adipose Tissue Proton Density Fat Fraction (Baseline, Week 24, and Week 48)
Change From Baseline in Mean L2-L4 Vertebral Bone Marrow Adipose Tissue Unsaturation Index (Baseline, Week 24, and Week 48)
Change from baseline in BM-MSC and AT-MSC potency, differentiation, senescence, and metabolic adaptation (Baseline and Week 24)

Eligibility information

Interventional Study: Effect of Caloric Restriction on BMAT/BM-MSCs Phenotype Inclusion Criteria: * 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 Exclusion Criteria: * 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 * Unstable cardiovascular disease * Uncontrolled hypertension * Current or recent use of any of the following medications: * Bisphosphonates * Estrogen * Denosumab * Gonadotropin-releasing hormone (GnRH) analogs * Glucocorticoids at a dose equivalent to at least 5 mg of prednisone daily for at least 1 month * Phenytoin * Thiazolidinediones * Insulin * Adrenal or anabolic steroids * Anticonvulsants * Anticoagulants * Pharmacological doses of vitamin D or vitamin A supplements * Contraindications to magnetic resonance imaging (MRI), including: * Pacemaker * Metallic implants incompatible with MRI * Claustrophobia

Study locations

General University Hospital in Prague, Prague, 12800 Czechia
Institute of Endocrinology, Prague, a state-funded organization established by the Ministry of Health of the Czech Republic., Prague, 12800 Czechia
Institute of Physiology of the Czech Academy of Sciences, Prague, 14200 Czechia

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-10-28.