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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 : April 17, 2018
Sponsor:
Collaborator:
Lund University
Information provided by (Responsible Party):
Oskar Hansson, Skane University Hospital

Brief Summary:

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

  Show Detailed Description

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 250 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 250 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

300 patients with either subjective cognitive decline (SCD; n=150) or mild cognitive impairment (MCI; n=150) 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

175 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 50 cases aged 40-65 years of age, 75 cases aged 66-79 years of age and 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:

  1. 140 cases with Frontotemporal dementia (FTD)-related disorders, including behavioral variant of FTD (bvFTD) (n=50), Progressive nonfluent aphasia (PNFA) (n=20), semantic dementia (SD) (n=20), Progressive supranuclear palsy (PSP) (n=30), Corticobasal degeneration (CBD) (n=20).
  2. 50 cases with subcortical Vascular dementia (VaD).
  3. 150 cases with either Parkinson's disease (PD) (n=50), Parkinson's disease with dementia (PDD) (n=30), Dementia with Lewy Bodies (DLB) (n=50), Multiple system atrophy (MSA) (n=20).

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




Primary Outcome Measures :
  1. Clinical diagnosis [ Time Frame: Clinical diagnosis at last 1 day visit ]
    Clinical diagnosis according to consensus group decision blinded to the diagnostic test

  2. 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


Secondary Outcome Measures :
  1. 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)

  2. 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

  3. 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. ]
  4. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

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


Contacts
Contact: Oskar Hansson, MD, Professor +46 (0)40 335036 oskar.hansson@med.lu.se
Contact: Erik Stomrud, MD, PhD erik.stomrud@med.lu.se

Locations
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 Not yet recruiting
Ängelholm, Sweden, SE-262 81
Contact: Per Johansson, MD, PhD         
Contact       per.a.johansson@skane.se   
Sponsors and Collaborators
Skane University Hospital
Lund University
Investigators
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     History of Changes
Other Study ID Numbers: BioFINDER 2
First Posted: June 5, 2017    Key Record Dates
Last Update Posted: April 17, 2018
Last Verified: April 2018
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

Keywords provided by Oskar Hansson, Skane University Hospital:
Early diagnosis, biomarker, PET, MRI, β-amyloid, tau, CSF, cognitive test

Additional relevant MeSH terms:
Lewy Body Disease
Parkinson Disease
Alzheimer Disease
Dementia
Cognitive Dysfunction
Atrophy
Aphasia
Supranuclear Palsy, Progressive
Multiple System Atrophy
Shy-Drager Syndrome
Aphasia, Broca
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Primary Progressive Nonfluent Aphasia
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Tauopathies
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Pathological Conditions, Anatomical
Speech Disorders
Language Disorders
Communication Disorders