Identification of Biomarkers Sensitive to Disease Progression in Patients With Mild Cognitive Impairment

NCT01425957 | Completed

• 2 other identifiers: WP5P0012011-A00985-36
• Study Type: interventional
• Target: 229
• Locations: 6 countries
• Sites: 13

Brief Summary

THE STUDY WILL BE A TWO-PART RESEARCH PART A and PART A extended:

1. 1.To implement a "common" MRI acquisition protocol in multiple centers across Europe (Pharma-COG partners).
2. 2.Apply the common MRI protocol on phantoms and human subjects to characterize, compare and minimize test-retest variability across the MR sites of WP5 for all the quantitative metrics that will be later assessed on patients.
3. 3.To develop a biomarker MATRIX (made of a combination of biological secondary endpoints) which is more sensitive than the changes observed in the loss of hippocampal volume (primary endpoint) and correlate with the neuropsychological progression and conversion (clinical secondary endpoints).
4. 4.To develop a biomarker MATRIX (made of a combination of biological secondary endpoints) at baseline which is more predictive of the loss of hippocampal volume (primary endpoint) and neuropsychological progression (clinical secondary endpoint) in MCI patients.
5. 5.To harmonize the biomarker MATRIX collection and qualify multiple centres across Europe

Conditions

MILD COGNITIVE IMPAIRMENT

Keywords

MEMORY and COGNITIVE IMPAIRMENT; ALZHEIMER DISEASE CONVERSION; Amyloid beta-Peptides

Outcome Measures

Primary Outcomes (2)

• Part A: Magnetic Resonance Imagery protocol

  The Magnetic Resonance Imagery protocol comprises a localiser or scout run, 4 structural-volumetric MRI sequences (i.e. 2 MP-RAGE, 1 FLAIR and 1 T2\*), a resting state functional MRI acquisition (i.e. rsfMRI), a diffusion tensor scan (i.e. DTI) that will be conducted at the magnetic field strength of 3T and a quantitative assessment of brain perfusion changes with a sequence of Arterial Spin Labelling (i.e. ASL) . The field map will be used for geometric distortion correction of the fMRI data. The main parameter of "efficacy" will be the reliability of the acquired MRI data (in terms of their correct acquisition and limited variability).

  Two times: One measure at day 1

• Part B: Changes of the hippocampal volume

  The primary endpoint will be changes of the hippocampal volume between the two groups (differentiated by the level of amyloid β1-42 in the cerebro-spinal fluid) and within the same group over time.

  2 or 3 times: every 18 months during 2 or 3 years (T0, T18 and/or T36)

Secondary Outcomes (7)

• Part B: Clinical assessment

  Every 6 months (screening, T6, T12, T18, T24, T30 and T36)

• Part B: Neuropsychology

  Every 6 months (screening, T6, T12, T18, T24, T30 and T36)

• Part B: Neurophysiology

  Every 6 months (T0, T6, T12, T18, T24, T30 and T36)

• Part B: Magnetic Resonance Imagery and functional MRI

  Every 6 months (screening, T0, T6, T12, T18, T24, T30 and T36)

• Part B: Blood drawing

  Every 6 months

Study Arms (1)

MCI Patient with Lumbar puncture

OTHER

PartB: Patients affected by amnestic Mild Cognitive Impairment (aMCI).

Procedure: Lumbar puncture

Interventions

Lumbar puncture PROCEDURE

All the patients will be divided in two groups based on their Aβ 1-42 levels measured in the cerebro-spinal fluid obtained form a lumbar puncture: in low Aβ1-42 (positive aMCI patients CSFP) and high Aβ1-42 (Negative aMCI patients CSFN). The threshold of Aβ1-42 used to divide the patient will be 500 (ng/L) based on Sjogren criteria (2001). Timeframe of lumbar punctures: every 18 months during 2 years (T0 and T18) or 3 years (T0, T18 and T36).

Also known as: Cerebrospinal fluid puncture

MCI Patient with Lumbar puncture

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PART A:

You may not qualify if:

• PART B:
• Written Informed Consent to participate in a up to 3 year imaging study
• Male and female aged between 55-90 years
• Memory complaint by patient or partner that is verified by a physician. (Memory complains expressed by the patients or their informant that the examiner considers to be relevant and exceed those expected for a patient of their age. The patient may or may not have symptoms of deficiency in other cognitive areas.)
• Abnormal memory functions documented by scoring 1 SD below the age-adjusted mean on the Logical Memory II subscale, (Delayed Paragraph Recall) from the Wechsler Memory Scale.
• General cognition and functional performance sufficiently preserved such that a diagnosis of Alzheimer's disease cannot be made by the site physician at the time of the screening visit.
• Mini-Mental State Exam score between 24 and 30 (inclusive)
• Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.
• Amnestic Mild Cognitive Impairment (MCI) (pure amnestic or multidomain)
• Geriatric Depression Scale less than 6
• Hachinski Modified Ischemic scale\< to 4
• Patient is untreated or under a permitted medication (Cholinesterase inhibitors and memantine, before the enrolment and newly prescriptions during the study, are permitted for aMCI patients.)
• At least 5 grades education
• Must speak (language) fluently
• Have a study partner with 10+ hr/wk contact (can be in person and telephone), accompanies to visits

Sponsors & Collaborators

• Qualissima: lead
• European Union: collaborator

Study Sites (13)

Université Lille 2, UL2 - Centre d'investigation clinique / Centre de Ressources biologiques 9301 - INSERM - Centre Hospitalier Régional et Universitaire de LILLE

Lille, 59307, France

Location

APHM, Hopital de la Timone, Service de Neurologie et Neuropsychologie

Marseille, 13385, France

Location

INSERM - CHU Purpan

Toulouse, 31059, France

Location

Hospital and Institute of the University of Duisburg and Essen - Department for Psychiatry and Psychotherapy, LVR Hospital Essen

Essen, 45147, Germany

Location

University Hospital of Leipzig - Department of Psychiatry

Leipzig, 04103, Germany

Location

Aristotle University of Thessaloniki, Greek Association of Alzheimer's disease and related disorders, Thessaloniki, Greece

Thessaloniki, 54643, Greece

Location

IRCCS-FBF - Ordine Ospedaliero San Giovanni di Dio, Fatebenefratelli, Istituto di Ricovero e Cura a Carattere Scientifico

Brescia, Provincia Lombardo-Veneta, 25125, Italy

Location

Neurofisiologia Clinica IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Padiglione Specialita' piano Fondi

Genoa, 16132, Italy

Location

IRCCS Fondazione SDN per la Ricerca e l'Alta Formazione in Diagnostica Nucleare di Napoli

Napoli, 80143, Italy

Location

Dipartimento di Specialità medico-chirurgiche e Sanità Pubblica, Sezione di Clinica Neurologica, Centro Disturbi della Memoria, Perugia, Italy

Perugia, 06132, Italy

Location

Università Cattolica del Sacro Cuore - Policlinico Agostino Gemelli Istituto di Neurologia - Neuropsychological and Neurorehabilitation Unit

Roma, 00168, Italy

Location

VUmc Alzheimercentrum

Amsterdam, 1007MB, Netherlands

Location

Institut d'Investigacions Biomèdiques August Pi I Sunyer, IDIBAPS

Barcelona, Catalonia, 08036, Spain

Location

Related Publications (1)

• Grady CL, Haxby JV, Horwitz B, Sundaram M, Berg G, Schapiro M, Friedland RP, Rapoport SI. Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type. J Clin Exp Neuropsychol. 1988 Oct;10(5):576-96. doi: 10.1080/01688638808402796.

  PMID: 3265710 BACKGROUND

Related Links

• The Alzheimer-Europe announcement webpage dedicated to PharmaCog project

MeSH Terms

Conditions

Cognitive Dysfunction; Plaque, Amyloid

Interventions

Spinal Puncture

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Giovanni Frisoni, MD, MP

  Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni di Dio Fatebenefratelli, Brescia, Italy

  STUDY DIRECTOR

• Mira Didic, MD

  Université de la Méditerranée, Service de Neurologie et Neuropsychologie, Marseille France

  PRINCIPAL INVESTIGATOR

• Jose-Luis Molinuevo, PhD

  Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

• Regis Bordet, MD

  Université Lille 2, Lille, France

  PRINCIPAL INVESTIGATOR

• Pierre Payoux, MD

  Institut National de la Santé et de la Recherche Médicale, Toulouse, France

  PRINCIPAL INVESTIGATOR

• Peter Schönknecht, MD

  Universitätsklinikum Leipzig, Department of Psychiatry and Nuclear Medicine, Leipzig, Germany

  PRINCIPAL INVESTIGATOR

• Jens Wiltfang, MD

  Universitaet Duisburg-Essen, Department of Psychiatry and Nuclear Medicine, Duisburg-Essen, Germany

  PRINCIPAL INVESTIGATOR

• Flavio Mariano Nobili, MD

  IRCCS Azienda Ospedaliera Universitaria San Martino-IST

  PRINCIPAL INVESTIGATOR

• Magda Tsolaki, MD

  Greek Association of Alzheimer's disease and related disorders, Thessaloniki, Greece

  PRINCIPAL INVESTIGATOR

• Lucilla Parnetti, MD

  Università di Perugia, Clinica Neurologica, Centro Disturbi della Memoria, Perugia, Italy

  PRINCIPAL INVESTIGATOR

• Paolo Maria Rossini, MD

  Università Cattolica del Sacro Cuore, Policlinico Agostino Gemelli, Istituto di Neurologia, Roma, Italy

  PRINCIPAL INVESTIGATOR

• Andrea Soricelli, MD

  Istituto di Ricerca Diagnostica e Nucleare, University of Naples Parthenope, Napoli, Italy

  PRINCIPAL INVESTIGATOR

• Philip Scheltens, MD

  VUmc Alzheimercentrum

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2011
• First Posted: August 30, 2011
• Study Start: December 1, 2011
• Primary Completion: August 1, 2015
• Study Completion: October 1, 2015
• Last Updated: November 2, 2015

Record last verified: 2015-10

Locations

DE (2); FR (3); ES (1); IT (5); GR (1); NL (1)