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Trial record 96 of 1901 for:    "bone marrow" | Recruiting, Not yet recruiting Studies

Effects of Tofacitinib on Body Composition, Bone Mineral Density and Bone Marrow Adiposity in Patients With Rheumatoid Arthritis: the TOFAT Project (TOFAT)

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ClinicalTrials.gov Identifier: NCT04175886
Recruitment Status : Recruiting
First Posted : November 25, 2019
Last Update Posted : June 25, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
University Hospital, Lille

Brief Summary:

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.


Condition or disease Intervention/treatment
Rheumatoid Arthritis Drug: Tofacitinib

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Study Type : Observational
Estimated Enrollment : 72 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Effects of Tofacitinib on Body Composition, Bone Mineral Density and Bone Marrow Adiposity in Patients With Rheumatoid Arthritis: the TOFAT Project
Actual Study Start Date : February 25, 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
Patients with rheumatoid arthritis
Patients with rheumatoid arthritis with an indication for tofacitinib: 5mgx2 per day
Drug: Tofacitinib
Patients will be treated with tofacitinib

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)



Primary Outcome Measures :
  1. Variation in visceral adiposity (VAT or Visceral Adipose Tissue) in cm² [ Time Frame: 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


Secondary Outcome Measures :
  1. Measurements of VAT in cm². [ Time Frame: at baseline ]
    Measurements of VAT in cm²

  2. Measurements of total fat mass (TBF) in kg, total lean mass (TLM) in kg, appendicular lean mass (aLM) in kg [ Time Frame: at baseline ]
    Measurements of total fat mass (TBF) in kg, total lean mass (TLM) in kg, appendicular lean mass (aLM) in kg

  3. Measurements of body fat percentage (%) [ Time Frame: at baseline ]
    Measurements of body fat percentage (%)

  4. Measurements of fat mass index (FMI) in kg/m² and skeletal muscle mass index (SMI) in kg/m² [ Time Frame: at baseline ]
    Measurements of fat mass index (FMI) in kg/m² and skeletal muscle mass index (SMI) in kg/m²

  5. Measurements of Bone mineral Density (BMD) in g/cm². [ Time Frame: at baseline ]
    Measurements of Bone mineral Density (BMD) in g/cm².

  6. Change in body fat percentage (% between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment (difference before/after). ]
    Change in body fat percentage (%) between measurement

  7. Change in total fat mass (TBF) between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment (difference before/after). ]
    Change in total fat mass (TBF) in kg between measurement

  8. Change in fat mass index (FMI) in kg/m², between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment (difference before/after). ]
    Change in fat mass index (FMI) in kg/m², between measurement

  9. Change in total lean mass (TLM, kg) and appendicular lean mass (aLM) in kg between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment (difference before/after). ]
    Change in total lean mass (TLM, kg) and appendicular lean mass (aLM) in kg between measurement

  10. Change in skeletal muscle mass index (SMI) in kg/m² between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment (difference before/after). ]
    Change in skeletal muscle mass index (SMI) in kg/m² between measurement

  11. Change in BMD (in g/cm²) at the lumbar spine (L1-L4) and non-dominant total hip between measurement [ Time Frame: 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

  12. Variation of bone remodelling markers (Cross-laps (CTX) and Type I procollagen N-terminal propeptide (P1NP)) between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment. ]
    Variation of bone remodelling markers (Cross-laps (CTX) and Type I procollagen N-terminal propeptide (P1NP)) between measurement

  13. Variation in leptin (ng/ml) between measurement. [ Time Frame: Before and after 6 months of tofacitinib treatment ]
    Variation in leptin (ng/ml) between measurement.

  14. Change in bone marrow adiposity (%) at the lumbar spine between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment. ]
    Change in bone marrow adiposity (%) at the lumbar spine between measurement

  15. Variation in Short Physical Performance Battery Protocol (SPPB) between measurement [ Time Frame: Before and after 6 months of tofacitinib treatment. ]
    Variation in Short Physical Performance Battery Protocol (SPPB) between measurement

  16. Changes in the parameters of the primary outcome and the secondary outcomes (n°2 to 8) [ Time Frame: Before and after 12 months of tofacitinib treatment. ]
    Changes in the parameters of the primary outcome and the secondary outcomes (n°2 to 8)


Biospecimen Retention:   Samples Without DNA
Whole blood, serum


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The study population is composed of adult patients with moderately to severely active RA for whom tofacitinib is indicated and who are followed in the department of rheumatology at Lille University Hospital
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • • 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,

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04175886


Contacts
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Contact: Jean-Guillaume Letarouilly, MD 0320445962 ext +33 jg.letarouilly@chru-lille.fr

Locations
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France
Lille University Hospital Recruiting
Lille, France
Contact: Jean-Guillaume Letarouilly, DR    +33320446926    jeanguillaume.letarouilly@chru-lille.fr   
Contact: Julien Paccou, PR    +33320446926    julien.paccou@chru-lille.fr   
Sponsors and Collaborators
University Hospital, Lille
Pfizer
Investigators
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Principal Investigator: Jean-Guillaume Letarouilly, MD University Hospital, Lille
Publications of Results:

Other Publications:
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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT04175886    
Other Study ID Numbers: 2018_38
2019-001159-37 ( EudraCT Number )
First Posted: November 25, 2019    Key Record Dates
Last Update Posted: June 25, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Lille:
rheumatoid arthritis
tofacitinib
body composition
bone marrow adiposity
bone marrow density
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Obesity
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action