The Swedish BioFINDER 2 Study (BioFINDER2)
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ClinicalTrials.gov Identifier: NCT03174938 |
Recruitment Status :
Recruiting
First Posted : June 5, 2017
Last Update Posted : November 7, 2023
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The Swedish BioFINDER 2 study is a new study that will launch in 2017 and extends the previous cohorts of BioFINDER 1 study (www.biofinder.se). BioFINDER 1 is used e.g. to characterize the role of beta-amyloid pathology in early diagnosis of Alzheimer's disease (AD) using amyloid-PET (18F-Flutemetamol) and Aβ analysis in cerebrospinal fluid samples. The BioFINDER 1 study has resulted in more than 40 publications during the last three years, many in high impact journals, and some the of the results have already had important implications for the diagnostic work-up patients with AD in the clinical routine practice.
The original BioFINDER 1 cohort started to include participants in 2008. Since then there has been a rapid development of biochemical and neuroimaging technologies which enable novel ways to the study biological processes involved in Alzheimer's disease in living people. There has also been a growing interest in the earliest stages of AD and other neurodegenerative diseases. With the advent of new tau-PET tracers there is now an opportunity to elucidate the role of tau pathology in the pathogenesis of AD and other tauopathies. The Swedish BioFINDER 2 study has been designed to complement the BioFINDER 1 study and to e.g. address issues regarding the role of tau pathology in different dementias and in preclinical stages of different dementia diseases. Further, the clinical assessments and MRI methods have been further optimized compared to BioFINDER 1.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Dementia Alzheimer Disease Parkinson Disease Lewy Body Disease Parkinson-Dementia Syndrome Frontotemporal Degeneration Semantic Dementia Progressive Nonfluent Aphasia Progressive Supranuclear Palsy Corticobasal Degeneration Multiple System Atrophy Mild Cognitive Impairment | Diagnostic Test: Flutemetamol F18 Injection Diagnostic Test: [18F]-RO6958948 Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and Ptau Diagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau | Not Applicable |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 1505 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Diagnostic |
Official Title: | The Swedish BioFINDER 2 Study |
Actual Study Start Date : | May 15, 2017 |
Estimated Primary Completion Date : | December 31, 2028 |
Estimated Study Completion Date : | December 31, 2028 |
Arm | Intervention/treatment |
---|---|
COHORT A: Cognitively healthy younger individuals (40-65 y)
We will recruit 300 cognitively healthy individuals from the Malmö Offspring study, which is an epidemiological study. The participants will be stratified according to a) family history of dementia in first degree relatives (with onset before 80 years of age) and b) APOE 4 genotype; i.e. 25% will have no family history and no APOE4 allele, 25% will have a family history and no APOE 4 allele, 25% will have no family history and at least one APOE 4 allele, 25% will have a family history and at least one APOE 4 allele. FOLLOW-UP FOR 8 YEARS Every 2 years new clinical, cognitive, neurological, and psychiatric assessments will be performed as well as CSF/blood sampling. MRI, Tau PET and Amyloid PET will be done every 4 years in all cases, and Tau PET and MRI every two years if the subject is amyloid positive at baseline. An auxiliary cohort (termed "Cohort A2") of 40 healthy individuals aged 20-40 years of age will also be included. |
Diagnostic Test: Flutemetamol F18 Injection
PET imaging of Abeta amyloid
Other Name: Vizamyl Diagnostic Test: [18F]-RO6958948 PET imaging of Tau aggregates Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid Diagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid |
COHORT B: Cognitively healthy elderly individuals (66-100 y)
We will recruit 300 cognitively healthy individuals from the Malmö/Lund region, where we will aim to include as many individuals as possible that did participate in the Malmö Diet and Cancer study during the early 1990's. The participants will be stratified according to a) family history of dementia in first degree relatives (with onset before 80 years of age) and b) APOE 4 genotype; i.e. 25% will have no family history and no APOE 4 allele, 25% will have a family history and no APOE 4 allele, 25% will have no family history and at least one APOE 4 allele, 25% will have a family history and at least one APOE 4 allele. FOLLOW-UP FOR 8 YEARS Every 2 years new clinical, cognitive, neurological, and psychiatric assessments will be performed as well as CSF/blood sampling. MRI, Tau PET and Amyloid PET will be done every 4 years in all cases, and Tau PET and MRI every two years if the subject is amyloid positive at baseline. |
Diagnostic Test: Flutemetamol F18 Injection
PET imaging of Abeta amyloid
Other Name: Vizamyl Diagnostic Test: [18F]-RO6958948 PET imaging of Tau aggregates Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid Diagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid |
COHORT C: SCD and MCI
750 patients with either subjective cognitive decline or mild cognitive impairment will be recruited in a consecutive fashion from the Skåne University Hospital and Ängelholm Hospital. We will only include cases where the medical doctor believes that the cognitive symptoms are caused by an incipient neurocognitive disorder. For example, all cases with evidence of brain amyloid pathology (i.e. an abnormal CSF Aβ42/40 ratio) will be included. FOLLOW-UP FOR 6 YEARS Every 12 months new clinical, cognitive, neurological, and psychiatric assessments will be performed. CSF/blood sampling, Tau PET (depends on further funding) and MRI will be done every 2 years. Amyloid PET will be performed at baseline and after 4 years. A auxiliary cohort ("Cohort C2") 150 cases with SCD/MCI where the doctor does not suspect incipient neurocognitive disorder, will undergo the same baseline investigations, but they will be followed up clinically only after 2, 4 and 8 y. |
Diagnostic Test: Flutemetamol F18 Injection
PET imaging of Abeta amyloid
Other Name: Vizamyl Diagnostic Test: [18F]-RO6958948 PET imaging of Tau aggregates Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid Diagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid |
COHORT D: Dementia due to Alzheimer's disease
400 patients with mild to moderate dementia due to Alzheimer's disease (AD) will be recruited from the Skåne University Hospital and Ängelholm Hospital in southern Sweden. We will include at least 50 cases aged 40-65 years of age, at least 200 cases aged 66-79 years of age and at least 50 cases aged 80-100 years of age. FOLLOW-UP FOR 2 YEARS Every 12 months new clinical, cognitive, neurological, and psychiatric assessments will be performed. CSF/blood sampling, Tau PET (depends on further funding) and MRI will be done at baseline and after 2 years. No Amyloid PET in this group. |
Diagnostic Test: [18F]-RO6958948
PET imaging of Tau aggregates Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid Diagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid |
COHORT E: Other dementias
Patients with primary neurodegenerative disorders other than Alzheimer's disease will be recruited:
FOLLOW-UP FOR 2 YEARS Every 12 months new clinical, cognitive, neurological, and psychiatric assessments will be performed. CSF/blood sampling, Tau PET (depends on further funding) and MRI will be done at baseline and after 2 years. No Amyloid PET in this group. |
Diagnostic Test: [18F]-RO6958948
PET imaging of Tau aggregates Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid Diagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid |
- Clinical diagnosis [ Time Frame: Clinical diagnosis at last 1 day visit ]Clinical diagnosis according to consensus group decision blinded to the diagnostic test
- Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline. ]Change in CDR-SB
- Rate of cognitive decline as measured by MMSE. [ Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline. ]Mini Mental State Examination (MMSE)
- Rate of cognitive decline as measured in ADL-function. [ Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline. ]ADL function will be determined using the Functional Assessment Questionnaire (FAQ) and The Amsterdam ADL scale
- Rate of volume change of structural MRI measures and amyloid PET [ Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline. ]
- Rates of change on cerebrospinal fluid AD biomarkers [ Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline. ]
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Ages Eligible for Study: | 20 Years to 100 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
COHORT A: Cognitively healthy younger individuals (40-65 years of age) INCLUSION CRITERIA
- Age 40-65 years
- Absence of cognitive symptoms as assessed by a physician with special interest in cognitive disorders.
- MMSE score 27-30 at screening visit.
- Do not fulfill the criteria for MCI or any dementia according to DSM-V.
- Speaks and understands Swedish to the extent that an interpreter is not necessary for the patient to fully understand the study information and cognitive tests.
EXCLUSION CRITERIA
- Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
- Current significant alcohol or substance misuse.
- Significant neurological or psychiatric illness.
- Refusing lumbar puncture, MRI or PET.
COHORT B: Cognitively healthy elderly individuals (66-100 years of age) INCLUSION CRITERIA
- Age 66-100 years
- Absence of cognitive symptoms as assessed by a physician with special interest in cognitive disorders.
- MMSE score 26-30 at screening visit.
- Do not fulfill the criteria for MCI or any dementia according to DSM-V.
- Speaks and understands Swedish to the extent that an interpreter is not necessary for the patient to fully understand the study information and cognitive tests.
EXCLUSION CRITERIA
- Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
- Current significant alcohol or substance misuse.
- Significant neurological or psychiatric illness.
- Refusing lumbar puncture, MRI or PET.
COHORT C: Subjective cognitive decline and mild cognitive impairment INCLUSION CRITERIA
- Age 40-100 years.
- Referred to the memory clinics due to cognitive symptoms experienced by the patient and/or informant. These symptoms do not have to be memory complaints, but could also be executive, visuospatial, language, praxis, psychomotor or social cognitive complaints.
- MMSE score of 24 - 30 points.
- Do not fulfill the criteria for any dementia (major neurocognitive disorder) according to DSM-V.
- The medical doctor (after clinical assessments, cognitive testing, CSF analyses and structural brain imaging) believes the cognitive complaints are caused by an incipient neurocognitive disorder of any sort. This is defined as any case fulfilling the criteria above (i.e. both SCD and MCI) with an abnormal CSF Aβ42/40 ratio, which is strongly associated with brain Aβ pathology and prodromal Alzheimer's disease. Further, cases with MCI (=minor neurocognitive impairment) due to either Parkinson's disease, Lewy body disease, vascular neurocognitive disorder or frontotemporal dementia (please see Appendix below for clinical criteria and references) can also be included.
- Speaks and understands Swedish to the extent that an interpreter is not necessary for the patient to fully understand the study information and cognitive tests.
EXCLUSION CRITERIA
- Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
- Current significant alcohol or substance misuse.
- Refusing lumbar puncture, MRI or PET.
COHORT D: Dementia due to Alzheimer's disease INCLUSION CRITERIA
- Age 40-100 years.
- Referred to the memory clinics due to cognitive symptoms experienced by the patient and/or informant. These symptoms do not have to be memory complaints, but could also be executive, visuospatial, language, praxis or psychomotor complaints.
- MMSE score of 12-26 points.
- Fulfill the criteria for dementia (major neurocognitive disorder) due to Alzheimer's disease (DSM-V).
- Speaks and understands Swedish to the extent that an interpreter was not necessary for the patient to fully understand the study information and cognitive tests.
EXCLUSION CRITERIA
- Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
- Current significant alcohol or substance misuse.
- Refusing lumbar puncture, MRI or PET.
COHORT E: Other dementias INCLUSION CRITERIA
- Age 40-100 years.
- Fulfill the criteria for dementia (major neurocognitive disorder) due to FTD, PDD, DLB or subcortical VaD alternatively the criteria for PD, PSP, MSA or CBS.
- Speaks and understands Swedish to the extent that an interpreter was not necessary for the patient to fully understand the study information and cognitive tests.
EXCLUSION CRITERIA
- Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
- Current significant alcohol or substance misuse.
- Refusing lumbar puncture, MRI or PET.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03174938
Contact: Oskar Hansson, MD, Professor | +46 (0)40 335036 | oskar.hansson@med.lu.se | |
Contact: Erik Stomrud, MD, PhD | erik.stomrud@med.lu.se |
Sweden | |
Memory Clinic, Skåne University Hospital | Recruiting |
Malmö, Sweden, SE-20502 | |
Contact: Erik Stomrud, MD, PhD erik.stomrud@med.lu.se | |
Memory Clinic, Hospital of Ängelholm | Recruiting |
Ängelholm, Sweden, SE-262 81 | |
Contact: Per Johansson, MD, PhD | |
Contact per.a.johansson@skane.se |
Principal Investigator: | Oskar Hansson, MD, Professor | Skåne University Hospital, and Lund University |
Responsible Party: | Oskar Hansson, Professor in Neurology; Consultant Neurologist, Skane University Hospital |
ClinicalTrials.gov Identifier: | NCT03174938 |
Other Study ID Numbers: |
BioFINDER 2 |
First Posted: | June 5, 2017 Key Record Dates |
Last Update Posted: | November 7, 2023 |
Last Verified: | November 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Early diagnosis, biomarker, PET, MRI, β-amyloid, tau, CSF, cognitive test |
Parkinson Disease Alzheimer Disease Dementia Aphasia Multiple System Atrophy Shy-Drager Syndrome Supranuclear Palsy, Progressive Lewy Body Disease Corticobasal Degeneration Frontotemporal Dementia Aphasia, Primary Progressive Pick Disease of the Brain Aphasia, Broca Primary Progressive Nonfluent Aphasia Cognitive Dysfunction |
Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Movement Disorders Synucleinopathies Neurodegenerative Diseases Tauopathies Neurocognitive Disorders Mental Disorders Cognition Disorders Speech Disorders Language Disorders Communication Disorders |