Clinical trial NCT01425957: Identification of Biomarkers Sensitive to Disease Progression in Patients With Mild Cognitive Impairment
Official title: Identification of Biomarkers Sensitive to Disease Progression in Patients With Mild Cognitive Impairment: a Two-part Clinical Study. PartA: Multisite MRI Acquisition, Protocol Harmonization. PartB: Identification of Biomarkers Sensitive to Disease Progression in Patients With Mild Cognitive Impairment: a Clinical Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: MILD COGNITIVE IMPAIRMENT
Keywords: MEMORY and COGNITIVE IMPAIRMENT
ALZHEIMER DISEASE CONVERSION
Amyloid beta-Peptides
Lead sponsor: Qualissima
Sponsor class: OTHER
Collaborators: name: European Union
First posted: 2011-08-30
Enrollment: 229
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: THE STUDY WILL BE A TWO-PART RESEARCH

PART A and PART A extended:

1. To implement a "common" MRI acquisition protocol in multiple centers across Europe (Pharma-COG partners).
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.

PART B: By collecting clinical, biochemical, neuroimaging, neuropsychological and neurophysiological data in Mild Cognitive Impairment patient, we aim to:

1. 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).
2. 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.
3. To harmonize the biomarker MATRIX collection and qualify multiple centres across Europe


Eligibility criteria: Inclusion Criteria:

* PART A:

Participants will be (i) healthy volunteers (between 50 and 80 years old) and/or (ii) subjects (between 50 and 80 years old), who will perform a 3T-MRI for reasons such as migraine, headache, auditory or visual symptoms, paresthesias, and whose scan will be negative (see exclusion criteria below). Such subjects will be selected and asked to perform additional sequences according to the part A study protocol.

* PART B:

Specific inclusion criteria:

1. Written Informed Consent to participate in a up to 3 year imaging study
2. Male and female aged between 55-90 years
3. 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.)
4. 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.
5. 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.
6. Mini-Mental State Exam score between 24 and 30 (inclusive)
7. Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5.
8. Amnestic Mild Cognitive Impairment (MCI) (pure amnestic or multidomain)
9. Geriatric Depression Scale less than 6
10. Hachinski Modified Ischemic scale\< to 4
11. 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.)
12. At least 5 grades education
13. Must speak (language) fluently
14. Have a study partner with 10+ hr/wk contact (can be in person and telephone), accompanies to visits
15. Willing and able to comply with the requirements of the study, as judged by the investigator

Exclusion Criteria:

* PART A:

  1. Ischaemic lesions already detected in a previous scan
  2. Head injury with loss of consciousness \> 24 hours
  3. Current substance abuse
  4. Current therapy with steroids or current chemotherapy
  5. Loss of weight \> 5 kg in the last 6 months
  6. Systemic disease with frequent involvement of the CNS (lupus, HIV, rheumatoid arthritis)
  7. CNS disease diagnosed by a specialist or in treatment (such as epilepsy, ictus)
  8. Cerebral metastasis or CNS primary tumour still benign (except for pituitary microadenoma)
  9. Suspected multiple sclerosis + MRI evidence of white matter lesions
  10. Suspected recent stroke + MRI evidence of infarct
  11. Aneurysm \> 10 mm and arteriovenous malformations (except for venous angioma)
  12. Dysgenesia of central nervous system
* PART B:

  1. Visual and auditory acuity inadequate for neuropsychological testing
  2. Enrolment in other trials or studies not compatible with study objectives (in particular, those with experimental drugs)
  3. History of significant neurological or psychiatric illnesses or presence of other diseases precluding enrolment.
  4. Use of forbidden medications
  5. Ferromagnetic implants and devices not eligible for MRI scanning. Brain malformation or other conditions that may complicate lumbar puncture
  6. Excluded Medication: Antidepressants with anti-cholinergic properties and within 4 weeks of the screening: Regular use of narcotic analgesics (\>2 doses per week), Use of neuroleptics with anti-cholinergic properties (e.g., chlorpromazine, thioridazine), Chronic use of other medications with significant central nervous system anticholinergic activity (e.g., diphenhydramine), Use of Anti-Parkinsonian medications (including Sinemet, amantadine, bromocriptine, pergolide, selegiline), Participation in any other investigational drug study (individuals may not participate in any drug study while participating in this protocol). Diuretic drugs should not be started or discontinued within 4 weeks prior to screening (Any change in diuretic medication during the study should be reported).

Primary outcomes:
measure: Part A: Magnetic Resonance Imagery protocol
timeFrame: Two times: One measure at day 1
measure: Part B: Changes of the hippocampal volume
timeFrame: 2 or 3 times: every 18 months during 2 or 3 years (T0, T18 and/or T36)
Secondary outcomes:
measure: Part B: Clinical assessment
timeFrame: Every 6 months (screening, T6, T12, T18, T24, T30 and T36)
measure: Part B: Neuropsychology
timeFrame: Every 6 months (screening, T6, T12, T18, T24, T30 and T36)
measure: Part B: Neurophysiology
timeFrame: Every 6 months (T0, T6, T12, T18, T24, T30 and T36)
measure: Part B: Magnetic Resonance Imagery and functional MRI
timeFrame: Every 6 months (screening, T0, T6, T12, T18, T24, T30 and T36)
measure: Part B: Blood drawing
timeFrame: Every 6 months
measure: Part B: Actigraphy
timeFrame: Every 6 months (T0, T6, T12, T18, T24, T30 and T36)
measure: Adverse events
timeFrame: Every 6 months (T0, T6, T12, T18, T24, T30 and T36)
Other outcomes:
Locations:
city: Lille
country: France
facility: Université Lille 2, UL2 - Centre d'investigation clinique / Centre de Ressources biologiques 9301 - INSERM - Centre Hospitalier Régional et Universitaire de LILLE
city: Marseille
country: France
facility: APHM, Hopital de la Timone, Service de Neurologie et Neuropsychologie
city: Toulouse
country: France
facility: INSERM - CHU Purpan
city: Essen
country: Germany
facility: Hospital and Institute of the University of Duisburg and Essen - Department for Psychiatry and Psychotherapy, LVR Hospital Essen
city: Leipzig
country: Germany
facility: University Hospital of Leipzig - Department of Psychiatry
city: Thessaloniki
country: Greece
facility: Aristotle University of Thessaloniki, Greek Association of Alzheimer's disease and related disorders, Thessaloniki, Greece
city: Brescia
country: Italy
facility: IRCCS-FBF - Ordine Ospedaliero San Giovanni di Dio, Fatebenefratelli, Istituto di Ricovero e Cura a Carattere Scientifico
state: Provincia Lombardo-Veneta
city: Genoa
country: Italy
facility: Neurofisiologia Clinica IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Padiglione Specialita' piano Fondi
city: Napoli
country: Italy
facility: IRCCS Fondazione SDN per la Ricerca e l'Alta Formazione in Diagnostica Nucleare di Napoli
city: Perugia
country: Italy
facility: Dipartimento di Specialità medico-chirurgiche e Sanità Pubblica, Sezione di Clinica Neurologica, Centro Disturbi della Memoria, Perugia, Italy
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore - Policlinico Agostino Gemelli Istituto di Neurologia - Neuropsychological and Neurorehabilitation Unit
city: Amsterdam
country: Netherlands
facility: VUmc Alzheimercentrum
city: Barcelona
country: Spain
facility: Institut d'Investigacions Biomèdiques August Pi I Sunyer, IDIBAPS
state: Catalunya
Study officials:
affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni di Dio Fatebenefratelli, Brescia, Italy
name: Giovanni Frisoni, MD, MP
role: STUDY_DIRECTOR
affiliation: Université de la Méditerranée, Service de Neurologie et Neuropsychologie, Marseille France
name: Mira Didic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut d'Investigacions Biomèdiques August Pi I Sunyer, Barcelona, Spain
name: Jose-Luis Molinuevo, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Université Lille 2, Lille, France
name: Regis Bordet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut National de la Santé et de la Recherche Médicale, Toulouse, France
name: Pierre Payoux, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätsklinikum Leipzig, Department of Psychiatry and Nuclear Medicine, Leipzig, Germany
name: Peter Schönknecht, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaet Duisburg-Essen, Department of Psychiatry and Nuclear Medicine, Duisburg-Essen, Germany
name: Jens Wiltfang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino-IST
name: Flavio Mariano Nobili, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Greek Association of Alzheimer's disease and related disorders, Thessaloniki, Greece
name: Magda Tsolaki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università di Perugia, Clinica Neurologica, Centro Disturbi della Memoria, Perugia, Italy
name: Lucilla Parnetti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Università Cattolica del Sacro Cuore, Policlinico Agostino Gemelli, Istituto di Neurologia, Roma, Italy
name: Paolo Maria Rossini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto di Ricerca Diagnostica e Nucleare, University of Naples Parthenope, Napoli, Italy
name: Andrea Soricelli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: VUmc Alzheimercentrum
name: Philip Scheltens, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.