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Patient- and care-related benefits of amyloid PET imaging

Organizational Data

DRKS-ID:
DRKS00030839
Recruitment Status:
Recruiting planned
Date of registration in DRKS:
2022-12-19
Last update in DRKS:
2024-03-22
Registration type:
Prospective

Acronym/abbreviation of the study

ENABLE

URL of the study

https://www.dzne.de/forschung/studien/klinische-studien/enable/

Brief summary in lay language

In the current medical care system, the majority of patients with dementia symptoms do not receive a diagnosis, or receive a diagnosis of unclear dementia. Even when patients do receive a specific diagnosis of Alzheimer's disease (AD) dementia, it is associated with diagnostic uncertainty in many cases. On behalf of the Federal Joint Committee (G-BA), the DZNE wants to find out with the ENABLE study whether an already approved imaging diagnostic procedure - amyloid positron emission tomography (PET) - has a positive influence on the further course of treatment in patients with unclear dementia. The amyloid PET examination serves to exclude or detect the beta-amyloid protein deposits in the brain that are typical for AD patients. The amyloid PET examination can thus contribute to increasing diagnostic certainty. The study will provide evidence to decide about reimbursing amyloid PET examinations by public health insurance.

Brief summary in scientific language

Two-arm, open-label, randomized, controlled, multicenter superiority trial in a parallel-group design with blinded endpoint collection and analysis. To demonstrate a patient-relevant benefit of amyloid PET compared with S3 guideline diagnosis without amyloid PET on dementia-relevant morbidity endpoints in patients with a dementia diagnosis of unclear or uncertain etiology, including a diagnosis of AD without sufficient certainty of diagnosis. Despite the use of already approved amyloid PET tracers, ENABLE was reclassified as a minimal-interventional clinical trial during the review process - due to the randomisation - and was resubmitted and positively evaluated after CTR.

Health condition or problem studied

ICD10:
F03 - Unspecified dementia
ICD10:
F00.0 - Dementia in Alzheimer disease with early onset
ICD10:
F00.1 - Dementia in Alzheimer disease with late onset
ICD10:
F00.2 - Dementia in Alzheimer disease, atypical or mixed type
ICD10:
F00.9 - Dementia in Alzheimer disease, unspecified
Healthy volunteers:
No

Interventions, Observational Groups

Arm 1:
The intervention is the performance of amyloid PET and the guideline-compliant diagnostic and therapeutic management based on the findings.
Arm 2:
The comparative intervention is guideline-compliant diagnostic and therapeutic management without performing an amyloid PET.

Endpoints

Primary outcome:
Ability to manage activities of daily living as measured by the Amsterdam Instrumental Activities of Daily Living Questionnaire© (A-IADL-Q) score 78 weeks after randomization.
Secondary outcome:
Occurrence of adverse effects of amyloid PET examination in a period of 2 weeks after the amyloid PET examination was performed. Measured via the specialist physician at the study site: - 26 weeks after randomization: change in etiologic dementia diagnosis, change in diagnostic certainty, change in diagnostic and therapeutic (especially medication administration or discontinuation) management. - Throughout the trial period: occurrence of adverse and serious adverse events (SAEs) and adverse drug reactions (ARs), mortality (also in the context of the safety assessment) Measured via patients and/or relatives by investigators blinded to the study condition: - 26, 52, 78, and 104 weeks after randomization: cognitive performance (ADAS-cog, MMSE, CDR-SB), quality of life, incl. health-related quality of life (QOL-AD scale), need for full inpatient or institutionalized outpatient care (institutionalization) or intensification of institutionalized outpatient care, and total duration and frequency of unplanned inpatient stays within one year (Questionnaire on Utilization of Medical and Nursing Services in Old Age [FIMA]). Measured via the Medical Review: Use of potentially inappropriate medications: PRISCUS list.

Study Design

Purpose:
Health care system
Allocation:
Randomized controlled study
Control:
  • Control group receives no treatment
Phase:
IV
Study type:
Interventional
Mechanism of allocation concealment:
Patients are randomized between the amyloid PET and control groups in a 1:1 ratio.
Blinding:
Yes
Assignment:
Parallel
Sequence generation:
The randomization code will be computer generated, stratifying by center and baseline A-IADL-Q (cut-off value 45) and implementing block randomization with block lengths that are unknown to the centers . Randomization will be performed centrally using a validated electronic tool after baseline assessments to determine inclusion and exclusion criteria have been completed. Trial sites must first register patients for the trial and confirm that inclusion and exclusion criteria are met; only then will they know the outcome of randomization.
Who is blinded:
  • Assessor
  • Data analyst

Recruitment

Recruitment Status:
Recruiting planned
Reason if recruiting stopped or withdrawn:
No Entry

Recruitment Locations

Recruitment countries:
  • Germany
Number of study centers:
Multicenter study
Recruitment location(s):
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Charite Universitätsmedizin Berlin Klinik für Psychiatrie und Psychotherapie Berlin
  • University medical center Rheinische Friedrich-Wilhelms-Universität Bonn Klinik für Neurodegenerative Erkrankungen und Gerontopsychiatrie Bonn
  • Other Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Zentrum für Klinische Forschung des DZNE e.V. Bonn
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Universitäts DemenzCentrum Universitätsklinikum an der TU Dresden Dresden
  • University medical center Universität Duisburg-Essen, Geriatriezentrum Haus Berge Essen
  • University medical center Universitätsklinikum Freiburg Klinik für Neurologie und Neurophysiologie Freiburg
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Universitätsmedizin Göttingen Klinik für Psychiatrie und Psychotherapie Göttingen
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Klinik für Neurologie Göttingen
  • University medical center Universitätsklinikum Hamburg-Eppendorf Klinik und Poliklinik für Psychiatrie und Psychotherapie Hamburg
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Universitätsklinik Köln Klinik und Poliklinik für Psychiatrie und Psychotherapie Köln
  • University medical center Universitätsklinik Köln Klinik für Neurologie Köln
  • University medical center Universitätsklinikum Leipzig Klinik für Neurologie Leipzig
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Otto-von-Guericke-Universität Magdeburg Institut für Kognitive Neurologie und Demenzforschung Magdeburg
  • University medical center Universitätsmedizin Mainz Klinik für Psychiatrie und Psychotherapie Mainz
  • Medical center Zentralinstitut für Seelische Gesundheit, J5 Mannheim
  • University medical center Universitätsmedizin Mannheim Neurologische Klinik Mannheim
  • University medical center Philipps-Universität Marburg Klinik für Neurologie Marburg
  • University medical center Philipps-Universität Marburg Klinik für Psychiatrie Marburg
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Klinikum der Universität München (LMU) Institut für Schlaganfall- und Demenzforschung (ISD) München
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Klinik für Psychiatrie und Psychotherapie München
  • University medical center Technische Universität München (TUM) Klinikum rechts der Isar Klinik und Poliklinik für Psychiatrie und Psychotherapie München
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Universitätsmedizin Rostock Klinik und Poliklinik für Psychosomatik und Psychotherapeutische Medizin Rostock
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Eberhard-Karls-Universität Tübingen Klinik für Psychiatrie und Psychotherapie Tübingen
  • University medical center Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. Universitätsklinikum Ulm Klinik für Neurologie Ulm
  • University medical center Universitätsklinikum Erlangen Psychiatrische und Psychotherapeutische Klinik Erlangen

Recruitment period and number of participants

Planned study start date:
2024-05-01
Actual study start date:
No Entry
Planned study completion date:
2027-10-31
Actual Study Completion Date:
No Entry
Target Sample Size:
1126
Final Sample Size:
No Entry

Inclusion Criteria

Sex:
All
Minimum Age:
50 Years
Maximum Age:
no maximum age
Additional Inclusion Criteria:
- Mild to moderate dementia syndrome. - Clinical Dementia Rating Scale (CDR-SB) greater than 0.5 and less than 3.0 and Mini-Mental Status Examination (MMSE) greater than 10 - Unclear diagnosis of dementia or uncertain diagnosis of Alzheimer's disease (diagnostic certainty less than 85 percent). - At least 15 percent probability of Alzheimer's disease, i.e., Alzheimer's disease cannot be excluded with certainty. - Diagnosis by examination of the cerebrospinal fluid is not possible because a) the patient has a contraindication to CSF puncture, b) the patient refuses CSF puncture or c) the diagnosis remains unclear after CSF puncture. - Patients who would agree in principle to undergo amyloid PET diagnostics and are willing to receive the results if randomised to the amyloid PET arm. - Written informed consent, either by the patient or the legal representative according to the presumed will of the patient - Accompanied by an authorised/qualified informant - Patients with valid insurance cover from a German statutory health insurance company

Exclusion Criteria

- Severe dementia (CDR score equal to 3 and/or an MMST score less than or equal to 10). - Mild cognitive impairment, CDR score less than or equal to 0.5, absence of cognitive impairment relevant to daily living - Patients in whom radiation exposure must be avoided - Pregnancy or breastfeeding at the time of the amyloid PET measurement (for women who are less than 12 months postmenopausal, a pregnancy test is carried out before the amyloid PET-measurement) - Patients who are currently participating in another clinical trial with investigational medication or within 5 half-lives of the investigational medication of another clinical trial

Addresses

Primary Sponsor

Deutsches Zentrum für Neurodegenerative Erkrankungen e. V.
Venusberg-Campus 1/99
53127 Bonn
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail
URL:
No Entry
Investigator Sponsored/Initiated Trial (IST/IIT):
Yes

Contact for Scientific Queries

DZNE Rostock/ Greifswald und Universitätsmedizin Rostock, Klinik und Poliklinik für Psychosomatik und Psychotherapeutische Medizin, Zentrum für Nervenheilkunde
Prof. Dr. Stefan Teipel
Gehlsheimer Str. 20
18147 Rostock
Germany
Telephone:
+49 (0) 381 / 494 9471
Fax:
+49 (0) 381 / 494 9472
Contact per E-Mail
URL:
No Entry

Contact for Public Queries

DZNE Rostock/ Greifswald und Universitätsmedizin Rostock, Klinik und Poliklinik für Psychosomatik und Psychotherapeutische Medizin, Zentrum für Nervenheilkunde
Prof. Dr. Stefan Teipel
Gehlsheimer Str. 20
18147 Rostock
Germany
Telephone:
+49 (0) 381 / 494 9471
Fax:
+49 (0) 381 / 494 9472
Contact per E-Mail
URL:
No Entry

Principal Investigator

DZNE Rostock/ Greifswald und Universitätsmedizin Rostock, Klinik und Poliklinik für Psychosomatik und Psychotherapeutische Medizin, Zentrum für Nervenheilkunde
Prof. Dr. Stefan Teipel
Gehlsheimer Str. 20
18147 Rostock
Germany
Telephone:
+49 (0) 381 / 494 9471
Fax:
+49 (0) 381 / 494 9472
Contact per E-Mail
URL:
No Entry

Sources of Monetary or Material Support

Public funding institutions financed by tax money/Government funding body (German Research Foundation (DFG), Federal Ministry of Education and Research (BMBF), etc.)

Gemeinsamer Bundesausschuss (G-BA)
10587 Berlin
Germany
Telephone:
No Entry
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Ethics Committee

Address Ethics Committee

Ethikkommission an der Medizinischen Fakultät der Universität Rostock im Institut für Rechtsmedizin
St.-Georg-Str. 108
18055 Rostock
Germany
Telephone:
+49-381-4949904
Fax:
No Entry
Contact per E-Mail
URL:
No Entry

Vote of leading Ethics Committee

Date of ethics committee application:
2022-07-18
Ethics committee number:
A 2022-0126
Vote of the Ethics Committee:
Approved
Date of the vote:
2022-08-08

Other Address Ethics Committee

Ethikkommission der Ärztekammer Nordrhein
Tersteegenstr. 9
40474 Düsseldorf
Germany
Telephone:
+49-211-43022272
Fax:
No Entry
Contact per E-Mail
URL:
http://www.aekno.de/aerztekammer/ethik-kommission

Vote of the Ethics Committee

Vote of the Ethics Committee:
Approved
Date of the vote:
2023-10-24

Further identification numbers

Other primary registry ID:
No Entry
EudraCT Number:
No Entry
Other secondary IDs:
2023-503705-10-00 - CTIS
UTN (Universal Trial Number):
No Entry
EUDAMED Number:
No Entry

IPD - Individual Participant Data

Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
Yes
IPD Sharing Plan:
The DZNE uses the data collected in the course of the audit, as well as other documents that are not generally known, to perform the main contract with the G-BA. Within the scope of the contract, the G-BA only receives the results of the evaluation after the audit has been conducted and evaluated. There is no transfer of audit data to the G-BA. A transfer of data to third parties may require the written consent of the G-BA; internal transfer within the DZNE within the scope of the audit is only permitted if reporting or information obligations require this. For the purpose of conducting the trial and its evaluation, the collected clinical data and imaging data will be shared in pseudonymized form with the subcontractors involved in the trial. After completion of the trial, the databases will be transferred to the DZNE. Patients will be informed about this in the patient information and agree to this by signing the consent form. Disclosure of information to authorities within the framework of legal provisions is permitted, but the G-BA must be informed. If publications with content related to the trial go beyond the contractual obligations, they will only be made after written approval by the G-BA. After completion of the originally planned trial and its analyses, research data will be used repseudonymously for further new analyses as secondary data or as selection criteria for new trials, depending on patient consent, and will be transferred anonymously to third parties. For this purpose, clinical and imaging data are stored in pseudonymized form on the DZNE scientific server after the end of the trial. Further transfer of (imaging) data to third parties in the context of scientific research beyond the trial will be done after application of the data to a DZNE internal Steering Committee according to the respective consent of the patients, which was documented in the trial consent, and if necessary the conclusion of a data use contract and / or material transfer agreement. A transfer of these data by the DZNE to third parties is only possible with the consent of the G-BA, if applicable. The scientific evaluation includes the optional biomaterial samples, the results from the dynamic PET acquisition and from the quantitative PET data analysis as well as health economic evaluations, these are not part of the service commissioned by the G-BA. These analyses also use data collected as part of the trial study. The agreements on the further use of the data and biomaterial samples are defined in the data use regulations and the biobank regulations of the clinical research of the DZNE.

Study protocol and other study documents

Study protocols:
No Entry
Study abstract:
No Entry
Other study documents:
No Entry
Background literature:
No Entry
Related DRKS studies:
No Entry

Publication of study results

Planned publication:
No Entry
Publikationen/Studienergebnisse:
No Entry
Date of first publication of study results:
No Entry
DRKS entry published for the first time with results:
No Entry

Basic reporting

Basic Reporting / Results tables:
No Entry
Brief summary of results:
No Entry