The Clinical Impact of the Novel Alzheimer's Blood-based Biomarkers

NCT06246019 | Enrolling By Invitation

• 1 other identifier: 15225
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to determine whether the early adoption of blood-based biomarkers for Alzheimer's disease is associated with an impact on etiological diagnosis, patient's management, emotional impact, patient's preferences and cost-effectiveness in patients presenting with cognitive complaints in a Cognitive Disorders Unit from a public hospital. The main questions it aims to answer are:

• Perform a blood extraction for blood-based biomarkers analysis at the beginning of the study.
• Complete specific scales in each visit. Researchers will compare the group in which blood biomarkers are delivered at 3 months with the group in which they are delivered at 9 months to assess whether early adoption of blood-based biomarkers is associated with an impact on etiological diagnosis, patient's management, emotional impact, patient's preferences and cost-effectiveness in a specialized memory unit.

Conditions

Alzheimer Disease; Cognitive Impairment; Dementia; Neurodegenerative Diseases; Frontotemporal Dementia; Lewy Body Disease; Vascular Dementia

Keywords

Blood-biomarkers; Alzheimer Disease; Diagnosis; Dementia; Cognitive impairment

Outcome Measures

Primary Outcomes (2)

• Etiological diagnosis

  The proportion of patients for whom an etiologic diagnosis is reached with very high confidence (≥90%) in each group at 3 and 9 months.

  9 months

• Suspicion of neurodegenerative disease

  The proportion of patients for whom a suspicion of neurodegenerative disease is reached as etiology with very high confidence (≥90%) in each group at 3 and 9 months.

  9 months

Secondary Outcomes (5)

• Number of tests for etiological diagnosis

  9 months

• Number of tests for a suspicion of neurodegenerative disease

  9 months

• Neurologist diagnoses over time

  9 months

• Neurologist confidence in the etiological diagnosis, which is is collected through the PLASMAR questionnaire at each visit.

  9 months

• Neurologist confidence in the suspicion of neurodegenerative disease, which is is collected through the PLASMAR questionnaire at each visit.

  9 months

Other Outcomes (5)

• Number of patients whose clinical management in the Cognitive Disorders Unit changes

  9 months

• Emotional impact of blood-based biomarkers on patient and study partner/caregiver

  9 months

• Impact of blood-based biomarkers on patient's quality of life

  9 months

Study Arms (2)

Early Blood-based biomarkers Arm

The results of the blood-based biomarkers will be communicated to the managing neurologist at visit 1 (at 3 months from baseline visit).

Diagnostic Test: Early adoption of blood-based biomarkers for Alzheimer's disease

Late Blood-based biomarkers Arm

The results of the blood-based biomarkers will be communicated to the managing neurologist at visit 2 (at 9 months from baseline visit).

Diagnostic Test: Early adoption of blood-based biomarkers for Alzheimer's disease

Interventions

Early adoption of blood-based biomarkers for Alzheimer's disease DIAGNOSTIC_TEST

A blood test will be performed to obtain plasma measures of Amyloid-β (Aβ) 42/40, phosphorylated tau (p-tau) 181, p-tau217, p-tau231 and Glial fibrillary acidic protein (GFAP) and Neurofilament light chain (NfL) and results will be disclosure to the early and late arms at different time points.

Early Blood-based biomarkers Arm; Late Blood-based biomarkers Arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

PLASMAR is prospective, unicentric, unblinded and randomized controlled study with blinded outcome ascertainment. Two hundred new patients will be consecutively recruited. All consecutive new patients who are visited for the first time to the outpatients' Memory Clinic at the Neurology Service (Hospital del Mar, Barcelona, Spain) will be considered for the study. Each patient will name a study partner to participate in this study, who will be considered for the study as well. In case the patient is diagnosed with dementia, a caregiver will be considered.

You may qualify if:

• Subjects ≥18 and ≤85 years old of any sex, gender, race or ethnicity.
• Individuals interested in participating in the study who understand the procedures that will be performed.
• The patient must have a complaint (reported by the patient or by a study partner/caregiver) of cognitive or behavioral impairment.
• The patient must satisfy the clinical diagnostic criteria for subjective cognitive decline, mild cognitive impairment, or mild dementia (defined as a Global deterioration scale score equal to 4), and a neurodegenerative disease such as AD is considered in the differential diagnosis.
• Agreement to undergo all the study procedures, complete all clinical visits according to protocol and capacity to give informed consent.
• The patient has undergone (maximum 12 months ago) or will undergo a dementia blood workup and MRI and/or CT scan before V1.
• In dementia patients, a study partner must be available for the duration of the protocol.

You may not qualify if:

• Any significant systemic illness or unstable medical condition that could make it difficult to comply with the protocol.
• Medical contraindications for any of the study procedures.
• Available AD's cerebrospinal fluid biomarkers levels or amyloid-PET at screening.
• The patient comes to the Memory Unit for reasons other than cognitive or behavioral impairment.
• Patients in which an etiological diagnosis is already made.
• The patient is currently participating or has participated in a clinical trial with an investigational pharmaceutical product.
• Women who are pregnant, planning to become pregnant, or lactating.

Sponsors & Collaborators

• Hospital del Mar Research Institute (IMIM): lead

Study Sites (1)

Hospital del Mar

Barcelona, Catalonia, 08003, Spain

Location

Related Publications (7)

• Altomare D, Barkhof F, Caprioglio C, Collij LE, Scheltens P, Lopes Alves I, Bouwman F, Berkhof J, van Maurik IS, Garibotto V, Moro C, Delrieu J, Payoux P, Saint-Aubert L, Hitzel A, Molinuevo JL, Grau-Rivera O, Gispert JD, Drzezga A, Jessen F, Zeyen P, Nordberg A, Savitcheva I, Jelic V, Walker Z, Edison P, Demonet JF, Gismondi R, Farrar G, Stephens AW, Frisoni GB; Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Consortium. Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial. JAMA Neurol. 2023 Jun 1;80(6):548-557. doi: 10.1001/jamaneurol.2023.0997.

  PMID: 37155177 BACKGROUND

• Grothe MJ, Moscoso A, Ashton NJ, Karikari TK, Lantero-Rodriguez J, Snellman A, Zetterberg H, Blennow K, Scholl M; Alzheimer's Disease Neuroimaging Initiative. Associations of Fully Automated CSF and Novel Plasma Biomarkers With Alzheimer Disease Neuropathology at Autopsy. Neurology. 2021 Sep 20;97(12):e1229-e1242. doi: 10.1212/WNL.0000000000012513.

  PMID: 34266917 BACKGROUND

• Janelidze S, Mattsson N, Palmqvist S, Smith R, Beach TG, Serrano GE, Chai X, Proctor NK, Eichenlaub U, Zetterberg H, Blennow K, Reiman EM, Stomrud E, Dage JL, Hansson O. Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia. Nat Med. 2020 Mar;26(3):379-386. doi: 10.1038/s41591-020-0755-1. Epub 2020 Mar 2.

  PMID: 32123385 BACKGROUND

• Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, Chamoun M, Savard M, Kang MS, Therriault J, Scholl M, Massarweh G, Soucy JP, Hoglund K, Brinkmalm G, Mattsson N, Palmqvist S, Gauthier S, Stomrud E, Zetterberg H, Hansson O, Rosa-Neto P, Blennow K. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020 May;19(5):422-433. doi: 10.1016/S1474-4422(20)30071-5.

  PMID: 32333900 BACKGROUND

• Simren J, Andreasson U, Gobom J, Suarez Calvet M, Borroni B, Gillberg C, Nyberg L, Ghidoni R, Fernell E, Johnson M, Depypere H, Hansson C, Jonsdottir IH, Zetterberg H, Blennow K. Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years. Brain Commun. 2022 Jul 4;4(4):fcac174. doi: 10.1093/braincomms/fcac174. eCollection 2022.

  PMID: 35865350 BACKGROUND

• Suarez-Calvet M, Karikari TK, Ashton NJ, Lantero Rodriguez J, Mila-Aloma M, Gispert JD, Salvado G, Minguillon C, Fauria K, Shekari M, Grau-Rivera O, Arenaza-Urquijo EM, Sala-Vila A, Sanchez-Benavides G, Gonzalez-de-Echavarri JM, Kollmorgen G, Stoops E, Vanmechelen E, Zetterberg H, Blennow K, Molinuevo JL; ALFA Study. Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Abeta pathology are detected. EMBO Mol Med. 2020 Dec 7;12(12):e12921. doi: 10.15252/emmm.202012921. Epub 2020 Nov 10.

  PMID: 33169916 BACKGROUND

• Thijssen EH, La Joie R, Strom A, Fonseca C, Iaccarino L, Wolf A, Spina S, Allen IE, Cobigo Y, Heuer H, VandeVrede L, Proctor NK, Lago AL, Baker S, Sivasankaran R, Kieloch A, Kinhikar A, Yu L, Valentin MA, Jeromin A, Zetterberg H, Hansson O, Mattsson-Carlgren N, Graham D, Blennow K, Kramer JH, Grinberg LT, Seeley WW, Rosen H, Boeve BF, Miller BL, Teunissen CE, Rabinovici GD, Rojas JC, Dage JL, Boxer AL; Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators. Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study. Lancet Neurol. 2021 Sep;20(9):739-752. doi: 10.1016/S1474-4422(21)00214-3.

  PMID: 34418401 BACKGROUND

Related Links

• Fluid Biomarkers and Translational Neurology group

Biospecimen

Retention: SAMPLES WITH DNA

Cerebrospinal fluid samples, serum and plasma samples will be processed and stored in the BIODEGMAR collection at the facilities of the Hospital del Mar Research Institute (IMIM). The sample collection of the present study has been registered in the National Registry of Biobanks, Instituto de Salud Carlos III (ISCIII), code: 0005744.

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Dementia; Neurodegenerative Diseases; Frontotemporal Dementia; Lewy Body Disease; Dementia, Vascular; Disease

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Cerebrovascular Disorders; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Marc Suárez-Calvet, MD PhD

  Hospital del Mar Research Insititute (IMIM)

  PRINCIPAL INVESTIGATOR

• Albert Puig-Pijoan, MD

  Hospital del Mar Research Insititute (IMIM)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Fluid Biomarkers and Translational Neurology Research Group

Study Record Dates

• First Submitted: January 23, 2024
• First Posted: February 7, 2024
• Study Start: February 7, 2024
• Primary Completion: May 1, 2025
• Study Completion: December 31, 2025
• Last Updated: February 28, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)