- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02321930
Musculoskeletal Ultrasound Assessment of Therapeutic Response of Tofacitinib in Rheumatoid Arthritis Patients
27 februari 2019 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
37
Fas
- Fas 4
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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California
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Los Angeles, California, Förenta staterna, 90095
- UCLA David Geffen School of Medicine, Division of Rheumatology
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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)
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Övrig: tofacitinib 5mg po bid
Open label with tofacitinib 5mg po bid
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
PDUS
Tidsram: 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 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.
|
Baseline, Week 2, Month 3
|
GSUS
Tidsram: 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.
|
Baseline, Week 2, Month 3
|
CDAI
Tidsram: Baseline, Week 2, Month 3
|
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
Tidsram: Baseline, Week 2, Month 3
|
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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
MBDA
Tidsram: 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.
|
Baseline, Week 2, Month 3
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Utredare
- Huvudutredare: Veena Ranganath, MD, MS, UCLA David Geffen School of Medicine, Division of Rheumatology
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
16 februari 2016
Primärt slutförande (Faktisk)
29 september 2017
Avslutad studie (Faktisk)
29 september 2017
Studieregistreringsdatum
Först inskickad
23 september 2014
Först inskickad som uppfyllde QC-kriterierna
16 december 2014
Första postat (Uppskatta)
22 december 2014
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
19 mars 2019
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
27 februari 2019
Senast verifierad
1 februari 2019
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- WI193025
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