Effects of Tofacitinib on Body Composition, Bone Mineral Density and Bone Marrow Adiposity in Patients With Rheumatoid Arthritis: the TOFAT Project
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Variation in visceral adiposity (VAT or Visceral Adipose Tissue) in cm²
研究概览
简要总结
Inflammatory rheumatic diseases (IRD), such as rheumatoid arthritis, are characterized by adverse changes in body composition. Lean mass and bone mineral density are usually reduced while adiposity (total fat mass, visceral adiposity…) is increased in comparison with healthy controls. Many factors may influence the body composition of those patients such as aging, Disease Modifying Anti-Rheumatic Drugs (DMARDs), nutrition and physical activity.
However, data on body composition and adverse changes under DMARDs in patients with rheumatoid arthritis (RA) are actually scarce. This is the case with tofacitinib (targeted synthetic DMARD or tsDMARD) while preliminary data let us think that this treatment may influence body composition and bone mineral density.
This study is going to be the first to focus on changes in body composition (fat mass and lean mass), bone mineral density and bone marrow adiposity under tofacitinib.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult patient's ≥18 years old with moderately to severely active Rheumatoid Arthritis (RA) (ACR/EULAR criteria )
- •Previously untreated with Janus Kinase (JAK) inhibitors
- •With an indication for tofacitinib will be eligible.
- •All patients will have to be treated with tofacitinib either alone or with methotrexate. -Healthy volunteers should be ≥18 years old.
排除标准
- •• treatment with more than three anti-Tumor Necrosis Factor alpha (TNFα). Patients who were receiving anti-TNFα will be required a washout period lasting at least five-half-lives before to start tofacitinib,
- •previously exposed to JAK inhibitors,
- •patients who were receiving non-anti-TNFα biologics (abatacept, tocilizumab, sarilumab or rituximab) will be required a washout period lasting at least five-half-lives before to start tofacitinib
- •Concomitant methotrexate (MTX) will be permitted if started ≥3 months prior to study start and at a stable dose (≤25 mg/week) for ≥4 weeks.
- •history or discovery of an osteoporotic fracture AND/OR T-score≤-3 if ≥50 years AND/OR Z-score ≤-3 if <50 years during the screening phase,
- •current treatment with oral corticosteroids higher than 10 mg prednisone/day,
- •pathologies or treatments that could affect the bone metabolism (breast cancer with aromatase inhibitors, gastrointestinal malabsorption, stomach cancer, primary hyperparathyroidism, uncontrolled hyperthyroidism…),
- •weight> 160 kg,
- •patients on restrictive diets or considering such a diet during the study period,
- •patients with an intense exercise program or planning to benefit from it during the study period,
研究组 & 干预措施
Healthy subjects
Healthy subjects matched to cases (1:1) on age (±5 years), sex, and menopausal status for women and body mass index (BMI, ±3 kg/m²)
Patients with rheumatoid arthritis
Patients with rheumatoid arthritis with an indication for tofacitinib: 5mgx2 per day
干预措施: Tofacitinib (Drug)
结局指标
主要结局
Variation in visceral adiposity (VAT or Visceral Adipose Tissue) in cm²
时间窗: Between the measurement before and after 6 months of tofacitinib treatment (difference before/after).
Variation in visceral adiposity (VAT or Visceral Adipose Tissue) in cm²
次要结局
- Measurements of VAT in cm².(at baseline)
- Measurements of total fat mass (TBF) in kg, total lean mass (TLM) in kg, appendicular lean mass (aLM) in kg(at baseline)
- Change in total lean mass (TLM, kg) and appendicular lean mass (aLM) in kg between measurement(Before and after 6 months of tofacitinib treatment (difference before/after).)
- Measurements of fat mass index (FMI) in kg/m² and skeletal muscle mass index (SMI) in kg/m²(at baseline)
- Measurements of body fat percentage (%)(at baseline)
- Change in total fat mass (TBF) between measurement(Before and after 6 months of tofacitinib treatment (difference before/after).)
- Measurements of Bone mineral Density (BMD) in g/cm².(at baseline)
- Change in fat mass index (FMI) in kg/m², between measurement(Before and after 6 months of tofacitinib treatment (difference before/after).)
- Variation in Short Physical Performance Battery Protocol (SPPB) between measurement(Before and after 6 months of tofacitinib treatment.)
- Changes in the parameters of the primary outcome and the secondary outcomes (n°2 to 8)(Before and after 12 months of tofacitinib treatment.)
- Change in body fat percentage (% between measurement(Before and after 6 months of tofacitinib treatment (difference before/after).)
- Change in BMD (in g/cm²) at the lumbar spine (L1-L4) and non-dominant total hip between measurement(Before and after 6 months of tofacitinib treatment (difference before/after).)
- Change in skeletal muscle mass index (SMI) in kg/m² between measurement(Before and after 6 months of tofacitinib treatment (difference before/after).)
- Variation of bone remodelling markers (Cross-laps (CTX) and Type I procollagen N-terminal propeptide (P1NP)) between measurement(Before and after 6 months of tofacitinib treatment.)
- Variation in leptin (ng/ml) between measurement.(Before and after 6 months of tofacitinib treatment)
- Change in bone marrow adiposity (%) at the lumbar spine between measurement(Before and after 6 months of tofacitinib treatment.)