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

Qualissima13 sites in 6 countries229 target enrollmentDecember 2011

ConditionsMILD COGNITIVE IMPAIRMENT

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: MILD COGNITIVE IMPAIRMENT
Sponsor: Qualissima
Enrollment: 229
Locations: 13
Primary Endpoint: Part B: Changes of the hippocampal volume
Status: Completed
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

THE STUDY WILL BE A TWO-PART RESEARCH

PART A and PART A extended:

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

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

Registry

clinicaltrials.gov

Start Date

December 2011

End Date

October 2015

Last Updated

10 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Qualissima

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.
•Specific inclusion criteria:
•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.
•Memory Box score must be at least 0.

Exclusion Criteria

•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
•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

Outcomes

Primary Outcomes

Part B: Changes of the hippocampal volume

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

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.

Part A: Magnetic Resonance Imagery protocol

Time Frame: Two times: One measure at day 1

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).

Secondary Outcomes

Part B: Neurophysiology(Every 6 months (T0, T6, T12, T18, T24, T30 and T36))
Part B: Blood drawing(Every 6 months)
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: Actigraphy(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))
Adverse events(Every 6 months (T0, T6, T12, T18, T24, T30 and T36))