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

NCT ID: NCT04175886

Last Updated: 2023-12-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

10 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-02-25

Study Completion Date

2023-05-08

Brief Summary

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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.

Detailed Description

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Conditions

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Rheumatoid Arthritis

Keywords

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rheumatoid arthritis tofacitinib body composition bone marrow adiposity bone marrow density

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Patients with rheumatoid arthritis

Patients with rheumatoid arthritis with an indication for tofacitinib: 5mgx2 per day

Tofacitinib

Intervention Type DRUG

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)

No interventions assigned to this group

Interventions

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Tofacitinib

Patients will be treated with tofacitinib

Intervention Type DRUG

Eligibility Criteria

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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,
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

University Hospital, Lille

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean-Guillaume Letarouilly, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Locations

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Lille University Hospital

Lille, , France

Site Status

Countries

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France

References

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Dodington DW, Desai HR, Woo M. JAK/STAT - Emerging Players in Metabolism. Trends Endocrinol Metab. 2018 Jan;29(1):55-65. doi: 10.1016/j.tem.2017.11.001. Epub 2017 Nov 27.

Reference Type BACKGROUND
PMID: 29191719 (View on PubMed)

Fleischmann RM, Huizinga TW, Kavanaugh AF, Wilkinson B, Kwok K, DeMasi R, van Vollenhoven RF. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis. RMD Open. 2016 Jul 26;2(2):e000262. doi: 10.1136/rmdopen-2016-000262. eCollection 2016.

Reference Type BACKGROUND
PMID: 27493790 (View on PubMed)

Tatsumi Y, Nakao YM, Masuda I, Higashiyama A, Takegami M, Nishimura K, Watanabe M, Ohkubo T, Okamura T, Miyamoto Y. Risk for metabolic diseases in normal weight individuals with visceral fat accumulation: a cross-sectional study in Japan. BMJ Open. 2017 Jan 16;7(1):e013831. doi: 10.1136/bmjopen-2016-013831.

Reference Type BACKGROUND
PMID: 28093438 (View on PubMed)

Book C, Karlsson MK, Akesson K, Jacobsson LT. Early rheumatoid arthritis and body composition. Rheumatology (Oxford). 2009 Sep;48(9):1128-32. doi: 10.1093/rheumatology/kep165. Epub 2009 Jul 13.

Reference Type RESULT
PMID: 19602478 (View on PubMed)

Haugeberg G, Uhlig T, Falch JA, Halse JI, Kvien TK. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000 Mar;43(3):522-30. doi: 10.1002/1529-0131(200003)43:33.0.CO;2-Y.

Reference Type RESULT
PMID: 10728744 (View on PubMed)

Toussirot E, Mourot L, Dehecq B, Wendling D, Grandclement E, Dumoulin G; CBT-506. TNFalpha blockade for inflammatory rheumatic diseases is associated with a significant gain in android fat mass and has varying effects on adipokines: a 2-year prospective study. Eur J Nutr. 2014 Apr;53(3):951-61. doi: 10.1007/s00394-013-0599-2. Epub 2013 Oct 31.

Reference Type RESULT
PMID: 24173963 (View on PubMed)

Marouen S, Barnetche T, Combe B, Morel J, Daien CI. TNF inhibitors increase fat mass in inflammatory rheumatic disease: a systematic review with meta-analysis. Clin Exp Rheumatol. 2017 Mar-Apr;35(2):337-343. Epub 2016 Dec 13.

Reference Type RESULT
PMID: 27974099 (View on PubMed)

Engvall IL, Tengstrand B, Brismar K, Hafstrom I. Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months. Arthritis Res Ther. 2010;12(5):R197. doi: 10.1186/ar3169. Epub 2010 Oct 21.

Reference Type RESULT
PMID: 20964833 (View on PubMed)

Tournadre A, Pereira B, Dutheil F, Giraud C, Courteix D, Sapin V, Frayssac T, Mathieu S, Malochet-Guinamand S, Soubrier M. Changes in body composition and metabolic profile during interleukin 6 inhibition in rheumatoid arthritis. J Cachexia Sarcopenia Muscle. 2017 Aug;8(4):639-646. doi: 10.1002/jcsm.12189. Epub 2017 Mar 18.

Reference Type RESULT
PMID: 28316139 (View on PubMed)

Letarouilly JG, Paccou J, Badr S, Chauveau C, Broux O, Clabaut A. Stimulatory Effect of Tofacitinib on Bone Marrow Adipocytes Differentiation. Front Endocrinol (Lausanne). 2022 Jul 6;13:881699. doi: 10.3389/fendo.2022.881699. eCollection 2022.

Reference Type DERIVED
PMID: 35873000 (View on PubMed)

Other Identifiers

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2019-001159-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2018_38

Identifier Type: -

Identifier Source: org_study_id