Rare DiseasesZSE-DUONCT03563677
Dual Guidance Structure for Evaluation of Patients With Unclear Diagnosis in Centers for Rare Diseases
A study testing dual expert guidance structure in people with Rare Diseases and Orphan Diseases, run by Wuerzburg University Hospital at 12 sites in Germany.
Trial summary
In people suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis is often ongoing for many years. Factors contributing to delayed diagnosis include the limited knowledge of health care professionals about rare diseases and their symptoms but also a psychiatric or psychosomatic… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Rare Diseases, Orphan Diseases
- What is being tested?
- dual expert guidance structure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,379 participants
- Where
- 12 sitesGermany
- Study dates
- 15 Oct 2018to 30 Sep 2022
- Phase
- Interventional
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- first contact with the Center for Rare Diseases for unclear diagnosis
- suspicion of a rare disease but no established diagnosis
- attending the Center for Rare Diseases as an outpatient
- written informed consent
Who cannot join
- age <12 years
- incomplete medical records including summary letters, imaging studies, blood tests etc.
- pre-diagnosed disease(s) explaining all symptoms
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Germany12 sites
Center for Rare Diseases ZSEA, University Hospital
Aachen, 52074
Center for Rare Diseases CeSER, St. Josef Hospital
Bochum, 44791
LWL-Universitätsklinikum der Ruhr-Universität
Bochum, 44791
Center for Rare Diseases FRZSE, UNiversity Hospital
Frankfurt, 60590
Center for Rare Diseases, Hannover Medical School
Hanover, 30625
Center for Rare Diseases MKSE, Otto von Guericke University
Magdeburg
Center for Rare Diseases, Medical Center
Mainz, 55131
Center for Rare Diseases, University Hospital
Münster, 48149
Center for Rare Diseases ZSER, University Hospital
Regensburg, 93053
Center for Rare Diseases, University Hospital
Tübingen, 72076
Center for Rare Diseases, University Hospital
Ulm, 89075
Center for Rare Diseases ZESE, University Hospital
Würzburg, Bavaria, 97080
About this study
Official title: Duale Lotsenstruktur Zur Abklärung Unklarer Diagnosen in Zentren für Seltene Erkrankungen
In people suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis is often ongoing for many years. Factors contributing to delayed diagnosis include the limited knowledge of health care professionals about rare diseases and their symptoms but also a psychiatric or psychosomatic (co-)morbidity obscuring the symptoms of the rare disease. The project ZSE-DUO will evaluate whether a combination of an expert in somatic medicine and a psychiatric/psychosomatic specialist will increase the rate of assured diagnoses in patients approaching a center of rare diseases (primary outcome), accelerate the process until a diagnosis is made, reduce the costs of diagnosing a patient, and lead to a higher satisfaction of patients and health care professionals. Furthermore, the project will evaluate whether the use of psychosomatic screening tools at registration of a patient in a center for rare diseases will help to guide the diagnostic process. Two cohorts of 682 patients each will be sequentially recruited over 9 plus 9 months: the Control group cohort (CG based on somatic expertise) and the Experimental group cohort (EG combined psychosomatic/somatic expertise Included will be persons from the age of at least 12 years presenting with symptoms and signs which are not explained by current diagnoses (as judged by the patient's primary care physician and a specialized physician at the center for rare diseases ZSE evaluating the medical records). Patients will be recruited from 11 German Centers for Rare Diseases associated with University hospitals in the cities of Aachen, Bochum, Frankfurt, Hannover, Magdeburg, Mainz, Münster, Regensburg, Tübingen, Ulm and Würzburg. Recruitment will be supported by a collaboration with the German patient organization representing many rare disease organizations ACHSE e.V. and a collaboration with the insurance companies Techniker Krankenkasse, IKK gesund plus and AOK Hessen who also provide data on costs of care. Data collection and analysis will be coordinated and performed by the Institute for Clinical Epidemiology and Biometry at the University of Würzburg, the Institute for Epidemiology, Social Medicine and Science of Health Care Systems in Hannover, and the Department of Medical Psychology in Hamburg. The project is funded by the Innovationsfond of the Federal Joint Committee in Germany.
- Conditions
- Rare Diseases, Orphan Diseases
- Being tested
- dual expert guidance structure
- Keywords
- psychosomatic, unclear diagnosis
- Medical subject headings
- Rare Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dual expert guidance structureOther
Two medical experts, one somatic specialist and one psychiatrist/psychosomatic specialist see all medical records and the patients together
| Study group | Role | What they receive |
|---|---|---|
| Usual care | No intervention | Standard evaluation process for patients approaching a center for rare diseases with an unclear diagnosis. The process includes the evaluation of complete medical records byan experienced physician, an outpatient visit to the center, and case discussion between experts. The process may also include an inpatient stay, a local case conference and a case conference between centers for rare diseases from different cities |
| New Innovative Care | Experimental | The innovative evaluation process includes the additional involvement of a psychiatrists/psychosomatic expert in all of the processes described for the usual care arm plus the option to use telemedicine in the process of evaluation in addition to outpatient and inpatient visits and to transfer the patient back into standard care (i.e., primary care physician, rehabilitation, psychological/psychosomatic specialized care, etc.) Receives: Other: dual expert guidance structure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnoses made
The number of diagnoses explaining the symptomatology of the patient made during the evaluation process
Measured: 12 months after signing the consent form
Secondary outcomes (6)
Time to diagnosis
The time it takes to make a diagnosis
Measured: 12 months after signing the consent form
Patient satisfaction with diagnostic process using ZUF-8
The patients' satisfaction with the diagnostic process is assessed in the total sample with the questionnaire ZUF-8 (Fragebogen zur Patientenzufriedenheit - patient satisfaction questionnaire) and in a randomly selected subsample of about 40 patients by structured telephone interviews.
Measured: 12 months after signing the consent form
Costs of the diagnostic process
estimated costs from first contact with the center for rare diseases until a diagnosis explaining the symptoms has been established
Measured: up to 12 months after signing the consent from
Patients' quality of life using EQ-5D and SF12 (or KIDSCREEN-10 for children)
Change in the patients' quality of life as assessed with the Quality of life questionnaires EQ-5D from the EuroQoL Group in all patients and Short Form 12 (SF-12) in patients 16 years and older. In patients younger than 16 years, the health-related quality of life questionnaire for children and adolescents KIDSCREEN-10 is used.
Measured: 12 months after signing the consent from
Physician satisfaction with new form of care using new questionnaire
The satisfaction of physicians working in the Centers fro Rare Diseases with the new form of care compared to standard care will be assessed by a newly developed questionnaire administered to all physicians involved in patient care in the 11 centers. For the development of the questionnaire, 3 focus groups of 10 physicians each will be questioned.
Measured: 30 months after the project start (end of the intervention period)
Value of screening instruments for psychiatric-psychosomatic (co-)morbidities
Performance of screening tools to identify patients with psychiatric-psychosomatic comorbidities against the judgement of a psychiatrist/psychosomatic expert seeing the patient (intervention group only)
Measured: 30 months after the project start (end of intervention period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2018
- Study start15 Oct 2018
- Primary completion31 Jan 2022
- Study completion30 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rare DiseasesStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Recruitment of 682 patients into control group during first 12 months of the project and, thereafter, recruitment of 682 patients during subsequent 12 months
- Masking
- None (open label)
- Enrolment
- 1,379 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wuerzburg University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Hannover Medical School, University Hospital, Aachen, Allianz Chronischer Seltener Erkrankungen ACHSE e.V., Goethe University, Universität Münster, St. Josef Hospital Bochum, Otto-von-Guericke University Magdeburg, University Medical Center Mainz, University Hospital Regensburg, University Hospital Tuebingen, University Hospital Ulm, IKK gesund plus, Techniker Krankenkasse, University of Wuerzburg, Universitätsklinikum Hamburg-Eppendorf, AOK Hessen, Ruhr University of Bochum
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03563677
- Sponsor's protocol ID
- ZSE-DUO_V1
- Acronym
- ZSE-DUO
- Status last verified
- Dec 2023
- First submitted
- 23 May 2018
- Last updated
- 13 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Schippers C, Volk D, de Zwaan M, Deckert J, Dieris-Hirche J, Herpertz S, Schulz JB, Hebestreit H; ZSE-DUO Arbeitsgruppe. [ZSE-DUO - dual guidance structure at the centre for rare diseases]. Inn Med (Heidelb). 2022 Jul;63(7):791-797. doi: 10.1007/s00108-022-01350-8. Epub 2022 Jun 2. German.
PubMed 35925266Hebestreit H, Zeidler C, Schippers C, de Zwaan M, Deckert J, Heuschmann P, Krauth C, Bullinger M, Berger A, Berneburg M, Brandstetter L, Deibele A, Dieris-Hirche J, Graessner H, Gundel H, Herpertz S, Heuft G, Lapstich AM, Lucke T, Maisch T, Mundlos C, Petermann-Meyer A, Muller S, Ott S, Pfister L, Quitmann J, Romanos M, Rutsch F, Schaubert K, Schubert K, Schulz JB, Schweiger S, Tuscher O, Ungethum K, Wagner TOF, Haas K; ZSE-DUO working group. Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study. Orphanet J Rare Dis. 2022 Feb 14;17(1):47. doi: 10.1186/s13023-022-02176-1.
PubMed 35164804Hebestreit H, Lapstich AM, Brandstetter L, Krauth C, Deckert J, Haas K, Pfister L, Witt S, Schippers C, Dieris-Hirche J, Maisch T, Tuscher O, Barlescu L, Berger A, Berneburg M, Britz V, Deibele A, Graessner H, Gundel H, Heuft G, Lucke T, Mundlos C, Quitmann J, Rutsch F, Schubert K, Schulz JB, Schweiger S, Zeidler C, Zeltner L, de Zwaan M; ZSE-DUO Working Group. Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design. EClinicalMedicine. 2023 Oct 6;65:102260. doi: 10.1016/j.eclinm.2023.102260. eCollection 2023 Nov.
PubMed 37855024Witt S, Kristensen K, Blomeke J, Hebestreit H, Wocker M, Pfister L, Bullinger M, Tuscher O, Deckert J, Graessner H, Lapstich AM, Zwaan M, Mundlos C, Quitmann JH. [Quality of Life and Experienced Distress of Patients Suspected of having a Rare (Chronic) Health Condition - Initial Findings from the ZSE-DUO Study]. Psychother Psychosom Med Psychol. 2023 Jan;73(1):9-15. doi: 10.1055/a-1814-3998. Epub 2022 Jul 6. German.
PubMed 35793670
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Duale Lotsenstruktur Zur Abklärung Unklarer Diagnosen in Zentren für Seltene Erkrankungen
- ClinicalTrials.gov ID
- NCT03563677
- Acronym / sponsor ID
- ZSE-DUO / ZSE-DUO_V1
- Conditions
- Rare Diseases, Orphan Diseases
- Keywords
- psychosomatic, unclear diagnosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,379 participants (actual)
- Lead sponsor
- Wuerzburg University HospitalUniversity, hospital or other
- Collaborators
- Hannover Medical School, University Hospital, Aachen, Allianz Chronischer Seltener Erkrankungen ACHSE e.V., Goethe University, Universität Münster, St. Josef Hospital Bochum, Otto-von-Guericke University Magdeburg, University Medical Center Mainz, University Hospital Regensburg, University Hospital Tuebingen, University Hospital Ulm, IKK gesund plus, Techniker Krankenkasse, University of Wuerzburg, Universitätsklinikum Hamburg-Eppendorf, AOK Hessen, Ruhr University of Bochum
- Study start
- 15 Oct 2018 (actual)
- Primary completion
- 31 Jan 2022 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 20 Jun 2018 (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.
In people suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis is often ongoing for many years. Factors contributing to delayed diagnosis include the limited knowledge of health care professionals about rare diseases and their symptoms but also a psychiatric or psychosomatic (co-)morbidity obscuring the symptoms of the rare disease. The project ZSE-DUO will evaluate whether a combination of an expert in somatic medicine and a psychiatric/psychosomatic specialist will increase the rate of assured diagnoses in patients approaching a center of rare diseases (primary outcome), accelerate the process until a diagnosis is made, reduce the costs of diagnosing a patient, and lead to a higher satisfaction of patients and health care professionals. Furthermore, the project will evaluate whether the use of psychosomatic screening tools at registration of a patient in a center for rare diseases will help to guide the diagnostic process. Two cohorts of 682 patients each will be sequentially recruited over 9 plus 9 months: the Control group cohort (CG based on somatic expertise) and the Experimental group cohort (EG combined psychosomatic/somatic expertise Included will be persons from the age of at least 12 years presenting with symptoms and signs which are not explained by current diagnoses (as judged by the patient's primary care physician and a specialized physician at the center for rare diseases ZSE evaluating the medical records). Patients will be recruited from 11 German Centers for Rare Diseases associated with University hospitals in the cities of Aachen, Bochum, Frankfurt, Hannover, Magdeburg, Mainz, Münster, Regensburg, Tübingen, Ulm and Würzburg. Recruitment will be supported by a collaboration with the German patient organization representing many rare disease organizations ACHSE e.V. and a collaboration with the insurance companies Techniker Krankenkasse, IKK gesund plus and AOK Hessen who also provide data on costs of care. Data collection and analysis will be coordinated and performed by the Institute for Clinical Epidemiology and Biometry at the University of Würzburg, the Institute for Epidemiology, Social Medicine and Science of Health Care Systems in Hannover, and the Department of Medical Psychology in Hamburg. The project is funded by the Innovationsfond of the Federal Joint Committee in Germany.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Recruitment of 682 patients into control group during first 12 months of the project and, thereafter, recruitment of 682 patients during subsequent 12 months
| Arm | Type | Receives |
|---|---|---|
| Usual care | No intervention | –Standard evaluation process for patients approaching a center for rare diseases with an unclear diagnosis. The process includes the evaluation of complete medical records byan experienced physician, an outpatient visit to the center, and case discussion between experts. The process may also include an inpatient stay, a local case conference and a case conference between centers for rare diseases from different cities |
| New Innovative Care | Experimental | Other: dual expert guidance structureThe innovative evaluation process includes the additional involvement of a psychiatrists/psychosomatic expert in all of the processes described for the usual care arm plus the option to use telemedicine in the process of evaluation in addition to outpatient and inpatient visits and to transfer the patient back into standard care (i.e., primary care physician, rehabilitation, psychological/psychosomatic specialized care, etc.) |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- first contact with the Center for Rare Diseases for unclear diagnosis
- suspicion of a rare disease but no established diagnosis
- attending the Center for Rare Diseases as an outpatient
- written informed consent
Key exclusion criteria (3 listed)
- age <12 years
- incomplete medical records including summary letters, imaging studies, blood tests etc.
- pre-diagnosed disease(s) explaining all symptoms
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 |
|---|---|---|
| dual expert guidance structureTwo medical experts, one somatic specialist and one psychiatrist/psychosomatic specialist see all medical records and the patients together | Other | New Innovative Care |
Primary outcome
Diagnoses made
Time frame: 12 months after signing the consent form
The number of diagnoses explaining the symptomatology of the patient made during the evaluation process
6 secondary outcomes
Time to diagnosis
Time frame: 12 months after signing the consent form
Patient satisfaction with diagnostic process using ZUF-8
Time frame: 12 months after signing the consent form
Costs of the diagnostic process
Time frame: up to 12 months after signing the consent from
Patients' quality of life using EQ-5D and SF12 (or KIDSCREEN-10 for children)
Time frame: 12 months after signing the consent from
Physician satisfaction with new form of care using new questionnaire
Time frame: 30 months after the project start (end of the intervention period)
Value of screening instruments for psychiatric-psychosomatic (co-)morbidities
Time frame: 30 months after the project start (end of intervention period)
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 13 Dec 2023.
- Background: PubMed 35925266Schippers C, Volk D, de Zwaan M, Deckert J, Dieris-Hirche J, Herpertz S, Schulz JB, Hebestreit H; ZSE-DUO Arbeitsgruppe. [ZSE-DUO - dual guidance structure at the centre for rare diseases]. Inn Med (Heidelb). 2022 Jul;63(7):791-797. doi: 10.1007/s00108-022-01350-8. Epub 2022 Jun 2. German.
- Background: PubMed 35164804Hebestreit H, Zeidler C, Schippers C, de Zwaan M, Deckert J, Heuschmann P, Krauth C, Bullinger M, Berger A, Berneburg M, Brandstetter L, Deibele A, Dieris-Hirche J, Graessner H, Gundel H, Herpertz S, Heuft G, Lapstich AM, Lucke T, Maisch T, Mundlos C, Petermann-Meyer A, Muller S, Ott S, Pfister L, Quitmann J, Romanos M, Rutsch F, Schaubert K, Schubert K, Schulz JB, Schweiger S, Tuscher O, Ungethum K, Wagner TOF, Haas K; ZSE-DUO working group. Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study. Orphanet J Rare Dis. 2022 Feb 14;17(1):47. doi: 10.1186/s13023-022-02176-1.
- Results publication: PubMed 37855024Hebestreit H, Lapstich AM, Brandstetter L, Krauth C, Deckert J, Haas K, Pfister L, Witt S, Schippers C, Dieris-Hirche J, Maisch T, Tuscher O, Barlescu L, Berger A, Berneburg M, Britz V, Deibele A, Graessner H, Gundel H, Heuft G, Lucke T, Mundlos C, Quitmann J, Rutsch F, Schubert K, Schulz JB, Schweiger S, Zeidler C, Zeltner L, de Zwaan M; ZSE-DUO Working Group. Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design. EClinicalMedicine. 2023 Oct 6;65:102260. doi: 10.1016/j.eclinm.2023.102260. eCollection 2023 Nov.
- Results publication: PubMed 35793670Witt S, Kristensen K, Blomeke J, Hebestreit H, Wocker M, Pfister L, Bullinger M, Tuscher O, Deckert J, Graessner H, Lapstich AM, Zwaan M, Mundlos C, Quitmann JH. [Quality of Life and Experienced Distress of Patients Suspected of having a Rare (Chronic) Health Condition - Initial Findings from the ZSE-DUO Study]. Psychother Psychosom Med Psychol. 2023 Jan;73(1):9-15. doi: 10.1055/a-1814-3998. Epub 2022 Jul 6. German.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing dual expert guidance structure in people with Rare Diseases and Orphan Diseases, run by Wuerzburg University Hospital at 12 sites 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 3 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 13 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites 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?
Diagnoses made (time frame: 12 months after signing the consent form). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03563677, which also lists 4 linked publications.
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 13 Dec 2023.