Musculoskeletal Ultrasound Assessment of Therapeutic Response of Tofacitinib in Rheumatoid Arthritis Patients
2019年2月27日 更新者：Dr. Veena Ranganath、University of California, Los Angeles
This proposal will evaluate if musculoskeletal ultrasound (MSUS) measures or multi-biomarker disease activity (MBDA) improve in patients treated with tofacitinib over 3 months, and whether early MSUS measures/MBDA can predict response to therapy.
調査の概要
詳細な説明
This is a pilot open-label trial of 25 RA patients treated with tofacitinib over 3 months.
The patients meeting inclusion criteria will be started on tofacitinib 5mg po bid.
Patients will be recruited from the UCLA Rheumatology Clinics.
Inclusion criteria will include the following: meeting ACR 1987 RA criteria, DAS28≥3.2, age≥18, and PDUS>10 (see below for more details).
Patients who are deemed unsafe to enroll will be excluded.
Ultrasound measures (PDUS/GSUS) and MBDA scores will be obtained at screen, baseline, 2 weeks, and 3 months.
In addition, we will also obtain HAQ-DI, CDAI, and DAS28 at the same time points.
In addition, we will have a 6 week visit for capturing adverse events, concomitant drugs, drug dispensation, and evaluation of adherence.
Currently, there are several US measures to evaluate therapeutic response in RA patients that have been used in the literature.
Some US studies evaluate all joints involved in RA, which is time consuming.
At present, there is no consensus as to the ideal ultrasound scoring system.
However, we will utilize a 34-joint US scoring system to evaluate response to therapy in this proposal (see Table 1).
Our research team has expertise in MSUS (given several workshops/lectures nationally) and we have proficiency in designing/conducting MSUS clinical trials.
We currently have 4 ultrasonography-rheumatologists at UCLA who are ACR certified in MSUS.
研究の種類
介入
入学 (実際)
37
段階
- フェーズ 4
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
-
-
California
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Los Angeles、California、アメリカ、90095
- UCLA David Geffen School of Medicine, Division of Rheumatology
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Patient must meet 1987 ACR criteria
- Age > 18 years of age
- Baseline DAS28/ESR>=3.2
- Stable concomitant DMARDs
- Stable prednisone <10mg or equivalent
- Power Doppler score of >=10
- Female subjects of childbearing potential must test negative for pregnancy
- Male and female subjects of childbearing potential must agree to use contraception throughout the study
- Negative QuantiFERON Gold test at screening
Exclusion Criteria:
- No active TB
- Prednisone >10 mg
- Pregnancy or breast feeding
- Prior treatment with tofacitinib
- Concomitant biologic therapy (TNF inhibitors, IL-6 inhibitors, etc.)
- Active infection with HIV, hepatitis B or C, or herpes zoster
Subjects with any uncontrolled clinically significant laboratory abnormality or any of the following laboratory abnormalities:
- Evidence of hematopoietic disorder or hemoglobin <9 g/dL
- Absolute lymphocyte count <0.75 x 109/L (<750/mm3)
- Absolute neutrophil count <1.2 x 109/L (<1200/mm3)
- Platelet count <100 x 109/L (<100,000/mm3)
- Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >1.5 times the upper limit of normal (x ULN)
- Estimated GFR <40 ml/min
- Subjects who have received live or live attenuated vaccines within 6 weeks prior to the first dose of study drug (or the zoster vaccine)
- Subjects who require concomitant treatment with medications that are potent inhibitors of cytochrome P450 3A4 (CYP3A4), both moderate inhibitors of CYP3A4 and potent inhibitors of CYP2C19, and potent CYP inducers (See Appendix)
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
他の：tofacitinib 5mg po bid
Open label with tofacitinib 5mg po bid
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
PDUS
時間枠：Baseline, Week 2, Month 3
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30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents PDUS.
The Power Doppler Synovitis Score (PDUS) ranges from 0 to 90.
Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation.
A higher value of the total score for PDUS represents more severe disease level.
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Baseline, Week 2, Month 3
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GSUS
時間枠：Baseline, Week 2, Month 3
|
30 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents GSUS.
The grey scale synovial hypertrophy score (GSUS) ranges from 0 to 90.
Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation.
A higher value of the total score for GSUS represents more severe disease level.
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Baseline, Week 2, Month 3
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CDAI
時間枠：Baseline, Week 2, Month 3
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CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity.
TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints.
PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity.
The total CDAI score range was 0-76, where higher scores indicate increased disease activity.
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Baseline, Week 2, Month 3
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DAS28/ESR
時間枠：Baseline, Week 2, Month 3
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TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints.
Patient Global Assessment of disease activity was scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity.
ESR lab value were included in the total calculation.
The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation.The scale ranges from 0 to 9.4, where higher values represent a higher disease activity.The complete formula to calculate DAS28/ESR is 0.56*sqrt(TJC) + (0.28*sqrt(SJC)) + (0.7*ln(ESR)) + (0.014*Patient Global*10).
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Baseline, Week 2, Month 3
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
MBDA
時間枠：Baseline, Week 2, Month 3
|
The multi-biomarker disease activity (MBDA) blood test assesses RA disease activity.
An algorithm of 12 markers is used to characterize RA disease activity on a scale of 1-100, where a score of 100 represents the highest level of disease activity present.
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Baseline, Week 2, Month 3
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Veena Ranganath, MD, MS、UCLA David Geffen School of Medicine, Division of Rheumatology
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Choate EA, Kaeley GS, Brook J, Altman RD, FitzGerald JD, Floegel-Shetty AR, Elashoff DA, Ranganath VK. Ultrasound detects synovitis in replaced and other surgically operated joints in rheumatoid arthritis patients. BMC Rheumatol. 2020 Feb 3;4:8. doi: 10.1186/s41927-019-0107-2. eCollection 2020.
- Kim SK, Jung UH, Kim JW, Choe JY. The beneficial effect of baricitinib on ultrasound-detected synovial inflammation and bone damage in rheumatoid arthritis: Preliminarily data from single center-based observational study for 24 weeks. Medicine (Baltimore). 2021 Jul 30;100(30):e26739. doi: 10.1097/MD.0000000000026739.
- Razmjou AA, Brook J, Elashoff D, Kaeley G, Choi S, Kermani T, Ranganath VK. Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis. BMC Rheumatol. 2020 Oct 19;4:55. doi: 10.1186/s41927-020-00153-4. eCollection 2020.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2016年2月16日
一次修了 (実際)
2017年9月29日
研究の完了 (実際)
2017年9月29日
試験登録日
最初に提出
2014年9月23日
QC基準を満たした最初の提出物
2014年12月16日
最初の投稿 (見積もり)
2014年12月22日
学習記録の更新
投稿された最後の更新 (実際)
2019年3月19日
QC基準を満たした最後の更新が送信されました
2019年2月27日
最終確認日
2019年2月1日
詳しくは
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