E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Detection of synovitis and tenosynovitis in the hands of patients with rheumatoid arthritis; Diagnostic performance of optical imaging in comparison with ultrasound and magnetic resonance imaging. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067132 |
E.1.2 | Term | Synovitis wrist |
E.1.2 | System Organ Class | 100000004859 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To explore whether there is a difference between findings among RA patients and healthy controls using Rheumascan of wrist, MCP and PIP joints as well as extensor tendon compartments of the wrist. |
At belyse om der er forskel på fund hos RA patienter og raske kontroller ved RS af hånd-, MCP- og PIP-led, samt ekstensorsener sener i håndleddet |
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E.2.2 | Secondary objectives of the trial |
To evaluate the reproducibility of Rheumascan findings among RA patients and healthy controls
To explore the sensitivity to changes of Rheumascan under treatment, among RA patients.
To determine sensitivity, specificity and accuracy of Rheumascan and ultrasound for detection of synovitis and tenosynovitis, with magnetic resonance imaging as standard reference.
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At undersøge om RS fund er reproducerbare hos RA patienter og raske kontroller.
At belyse sensitiviteten af RS for ændringer under behandling hos RA patienter.
At bestemme sensitivitet, specificitet og accuracy af RS og UL for påvisning af synovit and tenosynovit, med MRI som standard reference.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
A. – RA-patients.
• RA according to ACR/EULAR 2010 criteria (study A & B).
• Above 18 years of age (study A & B).
• At least one clinical inflamed joint in hands (study A & B).
• Clinical indication for escalating treatment (study B).
B. – Healthy controls.
• No inflammatory joint disease
• No chronic pain syndrome.
• No current joint symptoms
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A. – RA-deltagere.
• RA i henhold til ACR/EULAR 2010 kriterier (studium A & B).
• Alder over 18 år (studium A & B).
• Mindst et klinisk hævet led i hænder (studium A & B).
• Klinisk indikation for behandlingsoptrapning (studium B).
B. – Raske kontroller.
• Ingen kendt inflammatorisk led-sygdom.
• Ingen kendt kronisk smertesyndrom.
• Ingen aktuelle ledsymptomer.
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E.4 | Principal exclusion criteria |
Exclusion criteria
• Lack of ability to understand the information given about the study.
• Recent operation i the hands (within the last 4 weeks).
• Impaired renal function at inclusion (GFR < 90).
• Significant decreased liver function (liver enzymes > 2 x upper normal limit at time of inclusion).
• Previous allergy to contrast agents.
• Contraindications to ICG (Iod allergy, untreated hyperthyroidism, allergy to ICG-pulsion)
• Contraindications to MRI (pacemaker, claustrofobia, none compatible MRI metal in the body, allergy to Dotarem).
• Positive urine HCG among women in the age of fertility.
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• Manglende evne til at forstå informationen om studiet.
• Operation i hænderne indenfor de sidste 4 uger.
• Nedsat nyrefunktion ved screeningstidspunktet (GFR < 90).
• Stærkt nedsat leverfunktion (leverenzymer > 2 x øvre normalgrænse ved screeningstidspunktet).
• Tidligere kontrast allergier.
• Kontraindikationer for ICG (iod allergi, ubehandlet hyperthyroidisme, allergi for ICG-pulsion)
• Kontraindikationer for MRI (pacemaker, klaustrofobi, ikke MRI kompatibelt metal i kroppen, allergi for Dotarem).
• Positiv Urin HCG hos kvinder i den fertile alder
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E.5 End points |
E.5.1 | Primary end point(s) |
Study A
• Interscan agreement for Rheumascan using Intra-Class-Correlation coefficient and percentage absolute agreement.
Study B
• Sensitivity-to-change for quantitative evaluation of inflammation (synovitis and tenosynovits) in hands, evaluated after 6 months by Rheumascan, using standardized response mean (SRM.) |
Delstudium A
• Interscan overensstemmelse for RS ved Intra-Class-Correlation koefficient og procent absolut agreement.
Delstudium B
• Sensitivity-to-change for kvantitativ bedømmelse af inflammation (synovit og tenosynovit) i hænder, vurderet ved RS efter 6 måneder, bedømt med standardized response mean (SRM.). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After the last visit of the last participant. |
Efter sidste besøg, af sidste deltager. |
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E.5.2 | Secondary end point(s) |
Study A
• Intraobserver and interobserver agreement for Rheumascan assessed by Intra-Class-Correlation coefficient and percentage absolute agreement .
• Sensitivity, specificity and accuracy of Rheumascan and ultrasound for assessment of synovitis and tenosynovitis, with magnetic resonance imaging as standard reference.
• Difference between findings (synovitis and tenosynovitis) among RA patients and helathy controls using Rheumascan , assessed by Mann-Whitney U test.
Study B
Secundary endpoints:
• Sensitivity-to-change for quantitative evaluation of inflammation (synovitis and tenosynovits) in hands, evaluated after 3 month by Rheumascan, using standardized response mean (SRM.)
• Sensitivity-to-change for semi-quantitative scoring of inflammation (synovitis and tenosynovits) in hands using Rheumascan, evaluated after 3 and 6 months by standardized response mean (SRM)
• Changes in inflammatory activity evaluated by Rheumascan, ultrasound and magnetic resonance imaging, using Wilcoxon-Pratt test after 3 and 6 months.
• Correlation between changes in inflammatory activity evaluated by Rheumascan, ultrasound and magnetic resonance imaging during treatment using Spearman’s correlation after 3 and 6 months.
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Sekundære resultatmål:
Delstudium A
• Intraobservatør og interobservatør overensstemmelse for RS bedømt ved Intra-Class-Correlation koefficient og procent absolut agreement.
• Sensitivitet, specificitet og accuracy af RS og UL ved bedømmelse af synovit og tenosynovit i hænder, med MRI som standard reference,
• Forskel på fund (synovit og tenosynovit) ved RA og raske kontroller ved RS, bedømt ved Mann-Whitney U test.
Delstudium B
Sekundære resultatmål:
• Sensitivity-to-change for kvantitativ bedømmelse af inflammation (synovit og tenosynovit) i hænder, vurderet ved RS efter 3 måneder, bedømt med standardized response mean (SRM.).
• Sensitivity-to-change for semi-kvantitativ scoring af inflammation (synovit og tenosynovit) i hænder, ved RS, bedømt med standardized response mean (SRM.) ved tiden 3 og 6 måneder.
• Ændringer i inflammatorisk aktivitet bedømt ved RS, UL og MRI, vurderet ved Wilcoxon-Pratt test, til tiden 3 og 6 måneder.
• Korrelation mellem ændringer i inflammatorisk aktivitet bedømt ved RS, UL og MRI under behandling, vurderet ved Spearman’s korrelationsanalyse til tiden 3 og 6 måneder.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After the last visit of the last participant. |
Efter sidste besøg, af sidste deltager. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |