Multi-parameter Diagnostic Blood Test for the Diagnosis of Alzheimer's Disease (RH-VAL)

Validation Trial for a Multi-parameter Diagnostic Blood Test for the Diagnosis of Alzheimer's Disease

The purpose of this study is to validate a diagnostic test that combines different blood markers to identify and correctly classify patients with Alzheimer's disease (AD) compared to individuals with behavioural variant frontotemporal dementia (bvFTD, patient control) versus cognitively healthy individuals (healthy control).

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease

Detailed Description

The purpose of this study is to validate a new multi-parameter diagnostic test, on a well-characterised population based on new AD diagnostic criteria, that combines different types of markers, selected based on prior exploratory studies carried out by Raman Health Technologies.

• Study Type: Observational
• Enrollment (Anticipated): 700

Contacts and Locations

Study Locations

• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint Jan
  • Brussel, Belgium, B-1200
    • UCL St Luc
• France
  • Arras, France, 62000
    • Centre Hospitalier D'arras
  • Bron, France, 69500
    • Hôpital Neurologique Pierre Wertheimer
  • Lille, France, 59037
    • Clinique Neurologique CHRU
  • Paris, France, 75010
    • Centre Mémoire paris Nord Ile de France GH Saint-Louis Lariboisière Fernand Widal
  • Paris, France, 75013
    • Cognitive and Behavioral Disease Center and Alzheimer's Institute
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic
  • Barcelona, Spain, 08026
    • Hospital Sant Pau
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28046
    • Hospital La Paz
  • Madrid, Spain, 28007
    • Hospital Gregorio Marañón
  • Valladolid, Spain, 47003
    • Hospital de Valladolid
  • Cantabria
    • Santander, Cantabria, Spain, 39011
      • Hospital Marques de Valdecilla
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Virgen de la Arrixaca
  • San Sebastián
    • Donostia / San Sebastián, San Sebastián, Spain, 20009
      • CITA Alzheimer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

It is estimated that a sample of 500 patients (250 with AD and 250 with FTD) and 200 controls (700 individuals in total) will be sufficient to corroborate the hypothesis that permits validation of the new diagnostic test. The sample size estimate is based on a hypothesis of non inferiority between the new test and the test used in normal clinical practice, expecting a 10% delta of the 75% validity, sensitivity and specificity indices with an alpha error of 0.05 and a beta error of 0.20.

Description

Inclusion Criteria:

1. Healthy controls:

   • Aged between 50-80 years.
   • Men and women.
   • Assessment of the neuropsychological tests confirming the absence of cognitive impairment.
   • Prior to participant inclusion, obtaining the results of the CerebroSpinal Fluid marker analysis (beta-amyloid, Tau protein and p-Tau) carried out in the 24 months before recruitment.

2. Patients diagnosed with Alzheimer's disease (AD).

   • Aged between 50-80 years.
   • Men and women.
   • Patients meet the clinical criteria for Alzheimer's disease:
   • Prior to participant inclusion, results obtained from CerebroSpinal Fluid marker analysis (beta-amyloid, Tau protein and p-Tau) carried out in the 36 months before recruitment.

3. Patients with behavioural variant frontotemporal dementia and primary progressive aphasia: -

   • Aged between 50-80 years.
   • Men and women.
   • Patient meets the clinical criteria of behavioural variant frontotemporal dementia (bvFTD), or syndromes associated with temporal variants that affect language (primary progressive aphasia, agrammatic and semantic subgroups):

(Mild Cognitive Impairment) sub-study: Patients with mild cognitive impairment will be included

• Aged between 50-80 years.
• Men and women.
• Patient meets the clinical criteria for mild cognitive impairment:
• Clinical diagnostic criteria for mild cognitive impairment: NIA-Alzheimer's Association of America criteria, Alzheimer's Dementia, 2011
• Prior to participant inclusion, results obtained from cerebrospinal fluid marker analysis (beta-amyloid, Tau protein and p-Tau) carried out in the 12 months before recruitment.

Exclusion Criteria:

• Severe or acute systemic disease that could impede the participant's follow-up study: Advanced liver or kidney disease and disseminated neoplastic disease
• Addiction to alcohol or other drugs in the last two years based on Diagnostic and Statistical Manual of Mental Disorders IV criteria, except nicotine use, which is permitted
• Down's syndrome
• Moderate or severe head injury
• central nervous system infections (HIV, syphilis, borrelia, herpes simplex, suspected Creutzfeldt-Jakob disease)
• Endocrine alterations (thyroid alterations)
• Nutritional deficiency (vitamin B12, folic acid)
• Clinical history of stroke in the previous three months or neuroimaging evidence of clinically significant cardiovascular disease (e.g. strategic infarct or severe leukoencephalopathy).
• Neurological diseases (dysmyelinating disorders, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, subdural haematoma, brain tumours)
• Major psychiatric disorder (major depression or psychosis)
• Patients who do not have a clearly defined clinical diagnosis according to the study groups (inclusion/exclusion criteria)
• Disease which, in the investigator's or sponsor's judgement, may have a potentially significant influence and thus generate bias in the study markers.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Cognitively Healthy controls; The neuropsychological test assessment must confirm that there is no cognitive impairment. In the case of the cognitively healthy controls, CerebroSpinal Fluid tests performed within 24 months of inclusion will be accepted.
Alzheimer Disease; Patients with AD will be classified based on currently valid and updated diagnostic algorithms in the NIA-Alzheimer's Association of America Clinical Guidelines (2011).
Frontotemporal dementia; Inclusion criterion used will be prior diagnosis based on the diagnostic guidelines published by Dr. Rackovsky (Brain, 2011) for the behavioural variant; and those published by Prof. D. Neary (Neurology, 1998) for primary aphasia. A clinical and neuropsychological assessment is required, with the optional presence of alterations to the progranulin gene (and others) and there must be a compatible, previously performed imaging test (MRI, PET or SPECT) (predominantly frontal or frontotemporal atrophy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood markers	Multi-parameter determination: Raman laser and infrared spectroscopic markers, Metabolite-based markers (A02, A16, A22 ST01 F20 M30), Protein markers (A, A-T, B, PRO-B, C, C1, C2, PROGRANULIN), Biochemical markers (OXIDATIVE STRESS MARKERS, CTAN, ROUTINE BIOCHEMICAL MARKERS (GLUCOSE, TRIGLYCERIDES) and Genetic markers (ApoE, ApoC).	Up to 12 months

Collaborators and Investigators

• Sponsor: Raman Health Technologies, S.L.
• Investigators: Study Director: Javier Cabello, Raman Health Technologies, S.L.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): November 30, 2016
• Study Completion (Actual): October 18, 2017

Study Registration Dates

• First Submitted: March 17, 2015
• First Submitted That Met QC Criteria: March 31, 2015
• First Posted (Estimate): April 6, 2015

Study Record Updates

• Last Update Posted (Actual): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: RH-VAL-2013-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided