Rheumatoid ArthritisPANORANCT03267147
PREVALENCE OF Anti-CCP POSITIVITY AND SUBCLINICAL SIGNS OF INFLAMMATION IN PATIENTS WITH NEW ONSET OF NON-SPECIFIC MUSCULOSKELETAL SYMPTOMS
An observational study of Rheumatoid Arthritis, run by Fraunhofer Institute for Translational Medicine and Pharmacology ITMP at 1 site in Germany.
Trial summary
Non-interventional, prospective, observational study to assess the relative risk of anti-CCP positive patients to develop (subclinical) signs of inflammation in accordance with early Rheumatoid Arthritis (RA) in a population without pre-classified RA but new1 onset of non-specific musculoskeletal (MSK) symptoms in… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis
- How many people
- 986 participants
- Where
- 1 siteGermany
- Study dates
- 27 Apr 2017to 15 Feb 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: population without pre-classified RA but new onset of non-specific musculoskeletal (MSK) symptoms
Who may be able to join
- New onset of non-specific MSK symptoms, including, but not limited to, arthralgia of the hands and the large joints such as wrists, knees, and shoulders
- Written informed consent obtained prior to the initiation of any study protocol-required procedures
- General understanding of study procedure and informed consent
- Age ≥ 18 and ≤ 65 years
Who cannot join
- RA diagnosed according to modified EULAR/ACR (american college of rheumatology)-criteria
- Other known arthritis
- Other known reasons for MSK symptoms, e.g. mechanical, traumatic, etc.
- MSK symptoms previously reported at another (general) practice
- Alcohol, drug or chemical abuse
- Underage or incapable patients
Trial locations and contacts
1 site in 1 country.
About this study
Official title: PREVALENCE OF ANTI-CYCLIC CITRULLINATED PEPTIDE (Anti-CCP) POSITIVITY AND SUBCLINICAL SIGNS OF INFLAMMATION IN PATIENTS WITH NEW ONSET OF NON-SPECIFIC MUSCULOSKELETAL SYMPTOMS POSSIBLY RELATED TO EARLY RHEUMATOID ARTHRITIS IN GENERAL PRACTICES IN GERMANY
Non-interventional, prospective, observational study to assess the relative risk of anti-CCP positive patients to develop (subclinical) signs of inflammation in accordance with early Rheumatoid Arthritis (RA) in a population without pre-classified RA but new1 onset of non-specific musculoskeletal (MSK) symptoms in general practices in Germany and subsequent 36 months follow-up by rheumatologists
Read the detailed description
Studies of early arthritis cohorts have shown that a large number of early arthritis patients cannot be accurately diagnosed at their first visit, and hence are often referred as undifferentiated arthritis patients. If patients are found to be anti-CCP(+) when referred to the clinician, however, more than 90% develop RA within 3 years - in contrast to only 30% of the anti-CCP(-) patients. The presence of anti-CCP antibodies in undifferentiated arthritis therefore accurately predicts development of RA. Anti-CCP antibodies are very specific for RA, and they are produced at significant level very early in disease. The specificity of anti-CCP antibodies for the diagnosis of RA is high (94.1-99.0%). Moreover, it has been reported that anti-CCP antibodies can be present many years before the first visit to the clinic (up to 18 years). Furthermore, the presence of anti-CCP antibodies at the first visit to the clinician predicts radiographic progression, as demonstrated by many studies that have shown a strong association of anti-CCP positivity with the development of bone erosions.Early diagnosis of RA coupled with rational use of disease-modifying anti-rheumatic drugs (DMARD) has been shown to have a favourable effect on the course of the disease. Early and accurate diagnosis has therefore become increasingly important. Implementing anti-CCP quick tests in general practices could facilitate an early detection of RA or the allocation to a high risk RA group. This, in turn, would guarantee an early referral of the patient to a rheumatologist and together with other clinical examinations can aid in the early diagnosis and treatment. As has been shown in many studies an early intervention is vital to preserve joint function and to improve patient care. In this study, we want to assess the relative risk for patients derived from GPs in Germany with new onset of non-specific MSK symptoms and anti-CCP test positivity to develop (subclinical) signs of inflammation in accordance with early RA. Those patients will be identified in general practices and will be tested for anti-CCP status. Anti-CCP positive patients will then be introduced to a rheumatologist to validate anti-CCP status and examine presence of clinical signs of early RA in addition to subclinical signs of MSK inflammation. Furthermore, to focus on the possibility of early detection of anti-CCP before the onset of clinically active arthritis, patients will be followed-up by a rheumatologist until detection of early RA or up to 36 months in total. Early RA will be examined using standard of care for signs of inflammation including clinical examination for swollen and tender joints. In addition, ultrasound will be performed to assess joint inflammation as well as fluorescence optical imaging technique (Xiralite®) to sensitively illustrate changes in microvascularisation as a marker of subclinical inflammation. In cases of RA diagnosis, the study ends with the date of diagnosis and patients will receive treatment according to local guidelines earlier and medical care will be continued in clinical routine care conditions outside of the study. Moreover, the cooperation status between GPs and rheumatologists will be evaluated using qualitative interviews. Feasibility of the diagnosis of early RA in at risk patients as well as the feasibility of the transferral of these patients from the general practice to the rheumatologist will be assessed. Training of GPs for detection of early RA will be improved. Overall, the hypothesis of the study is that patients with new onset of unspecific MSK-symptoms and who are positive for anti-CCP, which both are risk factors for developing RA, will be earlier introduced to and monitored by a rheumatologist for proper clinical examination and potential treatment when establishing RA, which in turn will not only improve patient care, disease outcomes and quality of life, but might also be cost effective.
- Conditions
- Rheumatoid Arthritis
- Being tested
- no intervention is given
- Keywords
- Anti-CCP, rheumatoid arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no intervention is givenOther
no intervention is given
| Study group | Role | What they receive |
|---|---|---|
| antiCCP positive | Patients with a positive result in the anti-CCP quick test and positive in antiCCP ELISA will be examined by Rheumatologist for detection of RA symptoms and followed-up for 3 years or until RA diagnosis
no intervention is given Receives: Other: no intervention is given | |
| antiCCP negative | Patient with negative result in antiCCP quick test or negative antiCCP ELISA will be followed-up after one year (and 3 years for ELISA negative patients) with a short questionnaire if musculoskeletal symptoms are still present or if RA was diagnosed Receives: Other: no intervention is given |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the relative risk in patients with new onset of non-specific MSK symptoms who are anti-CCP positive to develop (subclinical) signs of inflammation in accordance with early RA in general practices in Germany
Determination if RA symptoms are present
Measured: every 6 months up to 3 years
Secondary outcomes (21)
diagnosis of RA in the group of anti-CCP positive patients with new onset of non-specific MSK symptoms
Measured: every 6 months up to 3 years
subclinical signs of inflammation using routine examination methods in anti-CCP positive patients
Measured: every 6 months up to 3 years
subclinical signs of inflammation using fluorescence optical imaging technique in anti-CCP positive patients
Measured: every 6 months up to 3 years
subclinical signs of inflammation using ultrasound in anti-CCP positive patients
Measured: every 6 months up to 3 years
anti-CCP level over time in anti-CCP positive patients
Measured: over 3 years
EQ5D
Questionnaire to assess Quality of Life profile of anti-CCP positive patients
Measured: every 6 months up to 3 years
SF36
Questionnaire to assess Quality of Life profile of anti-CCP positive patients
Measured: every 6 months up to 3 years
HAQ
Questionnaire to assess disability profile of anti-CCP positive patients
Measured: every 6 months up to 3 years
PHQ-9
Questionnaire to assess depression profile of anti-CCP positive patients
Measured: every 6 months up to 3 years
WPAI
Questionnaire to assess work ability profile of anti-CCP positive patients
Measured: every 6 months up to 3 years
assessment of time to disease in anti-CCP positive patients
Measured: every 6 months up to 3 years
assessment of correlation of anti-CCP level in anti-CCP positive patients
Measured: every 6 months up to 3 years
assessment quality of life (QoL) in anti-CCP positive patients
Measured: every 6 months up to 3 years
assessment work ability profile in anti-CCP positive patients
Measured: every 6 months up to 3 years
assessment subclinical signs of inflammation in anti-CCP positive patients
Measured: every 6 months up to 3 years
assessment risk of depression in anti-CCP positive patients
Measured: every 6 months up to 3 years
assessment of grade of disability in anti-CCP positive patients
Measured: every 6 months up to 3 years
diagnosis of RA in the group of ELISA test anti-CCP negative patients with new onset of non-specific MSK symptoms
Measured: 1 year
diagnosis of RA in the group of ELISA test anti-CCP negative patients with new onset of non-specific MSK symptoms
Measured: 3 years
diagnosis of RA in the group of quick test anti-CCP negative patients with new onset of non-specific MSK symptoms
Measured: 1 year
Qualitative assessment of general practitioners' (GP) routine care
qualitative interviews with the GP to evaluate current status of how patients with MSK symptoms are treated/forwarded in general practices
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2017
- Study start27 Apr 2017
- Primary completion16 Dec 2021
- Study completion15 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 986 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Goethe University
- Responsible party
- Principal investigator, Dr. Frank Behrens, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Investigators
- Frank Behrens, MD, Principal investigator, Fraunhofer IME
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03267147
- Sponsor's protocol ID
- TMP-1016_01
- Acronym
- PANORA
- Status last verified
- Mar 2022
- First submitted
- 4 Jul 2017
- Last updated
- 2 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PREVALENCE OF ANTI-CYCLIC CITRULLINATED PEPTIDE (Anti-CCP) POSITIVITY AND SUBCLINICAL SIGNS OF INFLAMMATION IN PATIENTS WITH NEW ONSET OF NON-SPECIFIC MUSCULOSKELETAL SYMPTOMS POSSIBLY RELATED TO EARLY RHEUMATOID ARTHRITIS IN GENERAL PRACTICES IN GERMANY
- ClinicalTrials.gov ID
- NCT03267147
- Acronym / sponsor ID
- PANORA / TMP-1016_01
- Conditions
- Rheumatoid Arthritis
- Keywords
- Anti-CCP, rheumatoid arthritis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 986 participants (actual)
- Lead sponsor
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMPUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Goethe University
- Study start
- 27 Apr 2017 (actual)
- Primary completion
- 16 Dec 2021 (actual)
- Study completion
- 15 Feb 2022 (actual)
- First posted
- 30 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Non-interventional, prospective, observational study to assess the relative risk of anti-CCP positive patients to develop (subclinical) signs of inflammation in accordance with early Rheumatoid Arthritis (RA) in a population without pre-classified RA but new1 onset of non-specific musculoskeletal (MSK) symptoms in general practices in Germany and subsequent 36 months follow-up by rheumatologists
Detailed description
Studies of early arthritis cohorts have shown that a large number of early arthritis patients cannot be accurately diagnosed at their first visit, and hence are often referred as undifferentiated arthritis patients. If patients are found to be anti-CCP(+) when referred to the clinician, however, more than 90% develop RA within 3 years - in contrast to only 30% of the anti-CCP(-) patients. The presence of anti-CCP antibodies in undifferentiated arthritis therefore accurately predicts development of RA. Anti-CCP antibodies are very specific for RA, and they are produced at significant level very early in disease. The specificity of anti-CCP antibodies for the diagnosis of RA is high (94.1-99.0%). Moreover, it has been reported that anti-CCP antibodies can be present many years before the first visit to the clinic (up to 18 years). Furthermore, the presence of anti-CCP antibodies at the first visit to the clinician predicts radiographic progression, as demonstrated by many studies that have shown a strong association of anti-CCP positivity with the development of bone erosions.Early diagnosis of RA coupled with rational use of disease-modifying anti-rheumatic drugs (DMARD) has been shown to have a favourable effect on the course of the disease. Early and accurate diagnosis has therefore become increasingly important. Implementing anti-CCP quick tests in general practices could facilitate an early detection of RA or the allocation to a high risk RA group. This, in turn, would guarantee an early referral of the patient to a rheumatologist and together with other clinical examinations can aid in the early diagnosis and treatment. As has been shown in many studies an early intervention is vital to preserve joint function and to improve patient care. In this study, we want to assess the relative risk for patients derived from GPs in Germany with new onset of non-specific MSK symptoms and anti-CCP test positivity to develop (subclinical) signs of inflammation in accordance with early RA. Those patients will be identified in general practices and will be tested for anti-CCP status. Anti-CCP positive patients will then be introduced to a rheumatologist to validate anti-CCP status and examine presence of clinical signs of early RA in addition to subclinical signs of MSK inflammation. Furthermore, to focus on the possibility of early detection of anti-CCP before the onset of clinically active arthritis, patients will be followed-up by a rheumatologist until detection of early RA or up to 36 months in total. Early RA will be examined using standard of care for signs of inflammation including clinical examination for swollen and tender joints. In addition, ultrasound will be performed to assess joint inflammation as well as fluorescence optical imaging technique (Xiralite®) to sensitively illustrate changes in microvascularisation as a marker of subclinical inflammation. In cases of RA diagnosis, the study ends with the date of diagnosis and patients will receive treatment according to local guidelines earlier and medical care will be continued in clinical routine care conditions outside of the study. Moreover, the cooperation status between GPs and rheumatologists will be evaluated using qualitative interviews. Feasibility of the diagnosis of early RA in at risk patients as well as the feasibility of the transferral of these patients from the general practice to the rheumatologist will be assessed. Training of GPs for detection of early RA will be improved. Overall, the hypothesis of the study is that patients with new onset of unspecific MSK-symptoms and who are positive for anti-CCP, which both are risk factors for developing RA, will be earlier introduced to and monitored by a rheumatologist for proper clinical examination and potential treatment when establishing RA, which in turn will not only improve patient care, disease outcomes and quality of life, but might also be cost effective.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| antiCCP positive | – | Other: no intervention is givenPatients with a positive result in the anti-CCP quick test and positive in antiCCP ELISA will be examined by Rheumatologist for detection of RA symptoms and followed-up for 3 years or until RA diagnosis no intervention is given |
| antiCCP negative | – | Other: no intervention is givenPatient with negative result in antiCCP quick test or negative antiCCP ELISA will be followed-up after one year (and 3 years for ELISA negative patients) with a short questionnaire if musculoskeletal symptoms are still present or if RA was diagnosed |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- population without pre-classified RA but new onset of non-specific musculoskeletal (MSK) symptoms
Key inclusion criteria (4 listed)
- New onset of non-specific MSK symptoms, including, but not limited to, arthralgia of the hands and the large joints such as wrists, knees, and shoulders
- Written informed consent obtained prior to the initiation of any study protocol-required procedures
- General understanding of study procedure and informed consent
- Age ≥ 18 and ≤ 65 years
Key exclusion criteria (6 listed)
- RA diagnosed according to modified EULAR/ACR (american college of rheumatology)-criteria
- Other known arthritis
- Other known reasons for MSK symptoms, e.g. mechanical, traumatic, etc.
- MSK symptoms previously reported at another (general) practice
- Alcohol, drug or chemical abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no intervention is givenno intervention is given | Other | antiCCP negative, antiCCP positive |
Primary outcome
Determination of the relative risk in patients with new onset of non-specific MSK symptoms who are anti-CCP positive to develop (subclinical) signs of inflammation in accordance with early RA in general practices in Germany
Time frame: every 6 months up to 3 years
Determination if RA symptoms are present
21 secondary outcomes
diagnosis of RA in the group of anti-CCP positive patients with new onset of non-specific MSK symptoms
Time frame: every 6 months up to 3 years
subclinical signs of inflammation using routine examination methods in anti-CCP positive patients
Time frame: every 6 months up to 3 years
subclinical signs of inflammation using fluorescence optical imaging technique in anti-CCP positive patients
Time frame: every 6 months up to 3 years
subclinical signs of inflammation using ultrasound in anti-CCP positive patients
Time frame: every 6 months up to 3 years
anti-CCP level over time in anti-CCP positive patients
Time frame: over 3 years
EQ5D
Time frame: every 6 months up to 3 years
SF36
Time frame: every 6 months up to 3 years
HAQ
Time frame: every 6 months up to 3 years
PHQ-9
Time frame: every 6 months up to 3 years
WPAI
Time frame: every 6 months up to 3 years
assessment of time to disease in anti-CCP positive patients
Time frame: every 6 months up to 3 years
assessment of correlation of anti-CCP level in anti-CCP positive patients
Time frame: every 6 months up to 3 years
assessment quality of life (QoL) in anti-CCP positive patients
Time frame: every 6 months up to 3 years
assessment work ability profile in anti-CCP positive patients
Time frame: every 6 months up to 3 years
assessment subclinical signs of inflammation in anti-CCP positive patients
Time frame: every 6 months up to 3 years
assessment risk of depression in anti-CCP positive patients
Time frame: every 6 months up to 3 years
assessment of grade of disability in anti-CCP positive patients
Time frame: every 6 months up to 3 years
diagnosis of RA in the group of ELISA test anti-CCP negative patients with new onset of non-specific MSK symptoms
Time frame: 1 year
diagnosis of RA in the group of ELISA test anti-CCP negative patients with new onset of non-specific MSK symptoms
Time frame: 3 years
diagnosis of RA in the group of quick test anti-CCP negative patients with new onset of non-specific MSK symptoms
Time frame: 1 year
Qualitative assessment of general practitioners' (GP) routine care
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Behrens, MD principal investigator
Fraunhofer IME
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rheumatoid Arthritis, run by Fraunhofer Institute for Translational Medicine and Pharmacology ITMP at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of the relative risk in patients with new onset of non-specific MSK symptoms who are anti-CCP positive to develop (subclinical) signs of inflammation in accordance with early RA in general practices in Germany (time frame: every 6 months up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.