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MILD COGNITIVE IMPAIRMENTNCT01425957

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

A study testing Lumbar puncture in people with MILD COGNITIVE IMPAIRMENT, run by Qualissima at 13 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 50 to 90 yearsHealthy volunteers can take part
Conditions the study is for
MILD COGNITIVE IMPAIRMENT
What is being tested?
Lumbar puncture
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
229 participants
Where
13 sitesin 6 countries
Study dates
Dec 2011to Oct 2015
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 90 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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:
  • Written Informed Consent to participate in a up to 3 year imaging study
  • Male and female aged between 55-90 years
Show all 19Show fewer
  • 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
  • Willing and able to comply with the requirements of the study, as judged by the investigator

Who cannot join

  • PART A:
  • Ischaemic lesions already detected in a previous scan
  • Head injury with loss of consciousness > 24 hours
  • Current substance abuse
  • Current therapy with steroids or current chemotherapy
  • Loss of weight > 5 kg in the last 6 months
Show all 20Show fewer
  • Systemic disease with frequent involvement of the CNS (lupus, HIV, rheumatoid arthritis)
  • CNS disease diagnosed by a specialist or in treatment (such as epilepsy, ictus)
  • Cerebral metastasis or CNS primary tumour still benign (except for pituitary microadenoma)
  • Suspected multiple sclerosis + MRI evidence of white matter lesions
  • Suspected recent stroke + MRI evidence of infarct
  • Aneurysm > 10 mm and arteriovenous malformations (except for venous angioma)
  • Dysgenesia of central nervous system
  • PART B:
  • Visual and auditory acuity inadequate for neuropsychological testing
  • Enrolment in other trials or studies not compatible with study objectives (in particular, those with experimental drugs)
  • History of significant neurological or psychiatric illnesses or presence of other diseases precluding enrolment.
  • Use of forbidden medications
  • Ferromagnetic implants and devices not eligible for MRI scanning. Brain malformation or other conditions that may complicate lumbar puncture
  • 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).

Trial locations and contacts

13 sites in 6 countries.

13 sites in 6 countries

Italy5 sites

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

    Brescia, Provincia Lombardo-Veneta, 25125

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

    Genoa, 16132

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

    Naples, 80143

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

    Perugia, 06132

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

    Roma, 00168

Other trials in Italy

France3 sites

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

    Lille, 59307

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

    Marseille, 13385

  • INSERM - CHU Purpan

    Toulouse, 31059

Other trials in France

Germany2 sites

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

    Essen, 45147

  • University Hospital of Leipzig - Department of Psychiatry

    Leipzig, 04103

Other trials in Germany

Greece1 site

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

    Thessaloniki, 54643

Other trials in Greece

Netherlands1 site

  • VUmc Alzheimercentrum

    Amsterdam, 1007MB

Other trials in Netherlands

Spain1 site

  • Institut d'Investigacions Biomèdiques August Pi I Sunyer, IDIBAPS

    Barcelona, Catalonia, 08036

Other trials in Spain

About this study

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

THE STUDY WILL BE A TWO-PART RESEARCH

PART A and PART A extended:

Read more
  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
Being tested
Lumbar puncture
Keywords
MEMORY and COGNITIVE IMPAIRMENT, ALZHEIMER DISEASE CONVERSION, Amyloid beta-Peptides
Medical subject headings
Cognitive Dysfunction, Plaque, Amyloid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lumbar punctureProcedure or surgery

    Also called Cerebrospinal fluid puncture

    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).

Study groups in NCT01425957
Study groupRoleWhat they receive
MCI Patient with Lumbar punctureOtherPartB: Patients affected by amnestic Mild Cognitive Impairment (aMCI).
Receives: Procedure: Lumbar puncture

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Two times: One measure at day 1

  2. 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.

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

Secondary outcomes (7)

  1. Part B: Clinical assessment

    • Mini-Mental State Examination (MMSE) (general cognitive functioning)
    • Clinical Dementia Rating (CDR)
    • Medical History
    • Physical exam
    • Neurological exams
    • Hachinski ischemic scale (differentiate Alzheimer's type dementia and multi-infarct dementia)
    • Geriatric Depression Scale (Depressive symptoms)
    • Functional Assessment Questionnaire (FAQ) (Activities of daily living)
    • Neuropsychiatric Inventory Questionnaire (NPI-Q) (Behaviour)

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

  2. Part B: Neuropsychology

    • ADAS-COG
    • Clock Drawing and Copying Test (Executive functions and planning abilities)
    • Rey Auditory Verbal Test (AVLT) (Memory)
    • Logical Memory Test I - Immediate Recall (Memory)
    • Digit Span Forward (Memory)
    • Digit Span Backward (Memory)
    • CANTAB Battery (visuospatial functions)
    • Letter fluency (Language)
    • Category Fluency (Language)
    • Boston Naming Test (BNT) (Language)
    • Trail Making Test (Attention)
    • Digit Symbol Substitution Test (Processing speed)

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

  3. Part B: Neurophysiology

    Electro-Encephalography in several conditions

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

  4. Part B: Magnetic Resonance Imagery and functional MRI

    The protocol comprises a localiser or scout run, 2 structural-volumetric MRI sequences (i.e. MPRAGE and FLAIR), one 2D structural analysis (i.e. T2*) a resting state functional MRI acquisition (i.e. rs-fMRI), 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 only in T18 and T24 timepoints for available patients).

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

  5. Part B: Blood drawing

    • ApoE (T0 only)
    • β amyloid in plasma (T0, T6, T12, T18, T24, T30 and T36)
    • Plasma and lymphocytes biomarkers (T0, T6, T12, T18, T24, T30 and T36)
    • PKC conformation (T0 and T18/T36)
    • amyloid β1-42 binding on erythrocytes (T0 and T18/T36)
    • Platelet APP-CTF (intracellular APP metabolites)(T0, T6, T12, T18, T24, T30 and T36)
    • RNA splicing analysis (T0, T6, T12, T18, T24, T30 and T36)

    Measured: Every 6 months

  6. Part B: Actigraphy

    Assessment of changes in position and acceleration for up to several weeks providing measures of activity. Additionally, sleep/wake and circadian rhythmicity can objectively be estimated from the recorded data by algorithms.

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

  7. Adverse events

    Any changes in the chronicity, severity, action taken, seriousness of a symptom or adverse event will be recorded by a qualified clinician (MD).

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionAug 2015
  4. Study completionOct 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
229 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01425957
Sponsor's protocol ID
WP5P001
Other IDs
2011-A00985-36
Status last verified
Oct 2015
First submitted
26 Aug 2011
Last updated
2 Nov 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 3265710

Questions about this trial

What is this clinical trial studying?

A study testing Lumbar puncture in people with MILD COGNITIVE IMPAIRMENT, run by Qualissima at 13 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Italy, France, Germany, Greece, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Magnetic Resonance Imagery protocol (time frame: Two times: One measure at day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01425957, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2015.

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