Patients With Cognitive DisturbancesShaTau7NCT02576821
Hippocampal Sclerosis and Amnesia Not Due to Alzheimer's Disease
A study testing Neurological examinations, Neuropsychological examinations and Clinical examinations in people with Patients With Cognitive Disturbances, run by Centre Hospitalier St Anne at 1 site in France.
Trial summary
Hippocampal Sclerosis (HS) leads to anterograde amnesia mimicking early Alzheimer's disease (AD) (so called HSA-nonAD). Recent studies showed that (a) the deficit of episodic memory as well as the level of hippocampal atrophy in bvFTD may be of similar severity to that observed in AD, even at initial presentation… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Patients With Cognitive Disturbances
- What is being tested?
- Neurological examinations, Neuropsychological examinations and Clinical examinations
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 141 participants
- Where
- 1 siteFrance
- Study dates
- 27 Jan 2016to 16 Oct 2023
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General inclusion criteria
- Be older than18 years old.
- Consulting in one of the centers (patients only)
- Sufficient cognitive capacities for the realization of the clinical and neuropsychological evaluations, left to the judgement by the investigator.
- Women old enough to procreate under effective contraception
- Signed consent
Show all 32Show fewer
- Absence of general or systemic disorders that may interfere with cognition.
- If available before inclusion, absence of brain lesions as determined by MRI that may account for even part of the clinical presentation.
- Patients with Hippocampal sclerosis non AD (n=40)
- Clinical criteria :
- CDR (Clinical Dementia Rating Scale) = 0.5 or 1
- Progressive amnestic syndrome of the hippocampal type, defined by a free recall score ≤ 17/48 and a total recall score ≤ 40/48 on the FCSRT.
- Biological criteria : Absence of Profile suggestive of AD on the study of the biomarkers of the CSF (IATI ratio > 0.8)
- Patients with Alheimer's Disase (n=40)
- Clinical criteria :
- CDR (Clinical Dementia Rating Scale) = 0.5 or 1
- Typical amnesic AD : Progressive amnestic syndrome of the hippocampal type, defined by a free recall score ≤ 17/48 and a total recall score ≤ 40/48 on the FCSRT, associated or not with others cognitive impairment
- Posterior Cortical Atrophy : initial presentation of progressive visual or visuospatial impairment; absence of ophthalmologic impairment with evidence of complex visual and/or visuospatial disorder on examination; a relatively preserved episodic memory
- Logopenic progressive aphasia : word retrieval deficits in spontaneous speech and confrontation naming, impaired repetition of sentences, errors in spontaneous speech and naming (eg, phonological errors), and relative sparing of word and object knowledge and motor speech.
- Biological criteria : CSF biomarkers suggestive of AD defined on CSF.
- Patients with DLFT (n=20) :
- Clinical criteria :
- Modifications of the personality and the social conducts in the foreground
- Compatible brain imaging with the diagnosis : profile of atrophy and/or hypometabolism in TEP-FDG (or hypoerfusion in Spect) compatible with the diagnosis of DFT and/or absence of atypie Biological criteria : No AD profile on CSF biomarkers
- Patients with CBD/PSP (n=20) (Armstrong et al., 2013)
- Corticobasal syndrome :
- at least one of the following signs : limb rigidity or akinesia, limb dystonia, limb myoclonusplus at least one of the following sign : orobuccal or limb apraxia, e) cortical sensory deficit, alien limb phenomena (more than simple levitation)
- Nonfluent/agrammatic variant of primary progressive aphasia: Effortful, agrammatic speech plus at least one of: a) impaired grammar/sentence comprehension with relatively preserved, single word comprehension, or b) groping, distorted speech production (apraxia of speech)
- Progressive supranuclear palsy syndrome :
- Three of the following items present: a) axial or symmetric limb rigidity or akinesia, b) postural instability or falls, c) urinary incontinence, d) behavioural changes, e) supranuclear vertical gaze palsy or decreased velocity of vertical saccades
- Normal controls (n=20):
- Absence of known psychiatric disorder Score on the Folstein Mini Mental Status (MMSE > or = 27) Normal neuropsychological assessment for the age and the educational level
Who cannot join
- Subject with a psychiatric evolutionary and/or badly checked pathology (left to the judgement of the investigator).
- Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
- Epileptics subjects, badly tolerant MRI (1.5T, 3T or 7T), Subject presenting contraindications to the MRI (if necessary, a blood pregnancy test will be performed before 7T MRI) (Pacemaker or stimulating neurosensory or implantable defibrillator, cochlear implants, eye or cerebral ferromagnetic foreign bodies close to nervous structures, metallic prostheses, agitation of the patient : not cooperative or agitated patients, very young children, claustrophobics subjects, pregnant women, neurosurgical ventriculoperitoneal shunt valves, brace)
- Known or supposed histories (< or = 5 years) of severe alcoholism or misuse of drugs
- Vascular, inflammatory or expansive, visible lesion in the MRI which can interfere on the criteria of diagnosis.
- No health insurance
- Pregnant, breast-feeding woman or planning a pregnancy in two years of follow-up.
- For controls : anomaly detected on the MRI in the appreciation of the investigator
Trial locations and contacts
1 site in 1 country.
France1 site
Neurologie de la mémoire et du langage, Service de Neurologie, Centre Hospitalier Sainte-Anne
Paris, 75014
About this study
Hippocampal Sclerosis (HS) leads to anterograde amnesia mimicking early Alzheimer's disease (AD) (so called HSA-nonAD). Recent studies showed that (a) the deficit of episodic memory as well as the level of hippocampal atrophy in bvFTD may be of similar severity to that observed in AD, even at initial presentation, leading to misdiagnosis in 22% of cases with post mortem diagnosis; (b) amnesia with HS due to microvascular lesion and microinfarcts can also cause impairment of episodic memory mimicking AD, without subcortical cognitive profile. Because these diseases involve distinct pathophysiological processes, they require different specific care and treatment. In consequence, it is very important to improve our knowledge about HS in order to identify its mechanism and improve the diagnosis.
Read the detailed description
Hippocampal sclerosis (HS) refers to neuronal cell loss and astrocytosis in subiculum and cornu ammonis subfields of the hippocampal formation unrelated to Alzheimer's disease pathology. In contrast to HS that affects younger adults with epilepsy, older individuals with HS have significant ante-mortem cognitive dysfunction but no epilepsy. Neuropathological studies demonstrated three main types of HS associated with aging: (a) HS-Ageing to refer to the disease with HS pathology in ageing individuals, observed in more than 10% of subjects aged over 85 years; (b) HS observed in the behavioural variant of frontotemporal dementia (bvFTD), HS being more frequent in tau-negative pathology, especially in FTLD-TDP. bvFTD patients may manifest severe episodic memory impairment and hippocampal atrophy; (c) HS associated with cortical or subcortical cerebral microinfarcts, which are invisible on conventional MRI. Cerebral microinfarcts are observed in 33% of elderly over 85 years in post-mortem studies.
HS leads to anterograde amnesia mimicking early Alzheimer's disease (AD) (so called HSA-nonAD). Recent studies showed that (a) the deficit of episodic memory as well as the level of hippocampal atrophy in bvFTD may be of similar severity to that observed in AD, even at initial presentation, leading to misdiagnosis in 22% of cases with post mortem diagnosis; (b) amnesia with HS due to microvascular lesion and microinfarcts can also cause impairment of episodic memory mimicking AD, without subcortical cognitive profile. Because these diseases involve distinct pathophysiological processes, they require different specific care and treatment. In consequence, it is very important to improve our knowledge about HS in order to identify its mechanism and improve the diagnosis.
- Conditions
- Patients With Cognitive Disturbances
- Being tested
- Neurological examinations, Neuropsychological examinations, Clinical examinations, MRI 3T, MRI 7T
- Keywords
- Amnesia, Alzheimer, hippocampal sclerosis, fronto-temporal lobar degeneration
- Medical subject headings
- Amnesia, Hippocampal Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurological examinationsOther
Neuropsychological examinationsOther
Clinical examinationsOther
MRI 3TRadiation
MRI 7TRadiation
| Study group | Role | What they receive |
|---|---|---|
| Patients with Hippocampal sclerosis non AD | Other | Patients with Hippocampal sclerosis non AD (n=40) Receives: Other: Neurological examinations; Other: Neuropsychological examinations; Other: Clinical examinations; Radiation: MRI 3T; Radiation: MRI 7T |
| Patients with Alhzeimer's Disase | Other | Patients with Alhzeimer's Disase (n=40) Receives: Other: Neurological examinations; Other: Neuropsychological examinations; Other: Clinical examinations; Radiation: MRI 3T; Radiation: MRI 7T |
| Patients with DLFT | Other | Patients with DLFT (n=20) Receives: Other: Neurological examinations; Other: Neuropsychological examinations; Other: Clinical examinations; Radiation: MRI 3T; Radiation: MRI 7T |
| Patients with CBD/PSP | Other | Patients with CBD/PSP (n=20) Receives: Other: Neurological examinations; Other: Neuropsychological examinations; Other: Clinical examinations; Radiation: MRI 3T; Radiation: MRI 7T |
| Normal controls | Other | Normal controls (n=20) Receives: Other: Neurological examinations; Other: Neuropsychological examinations; Other: Clinical examinations; Radiation: MRI 3T; Radiation: MRI 7T |
What is being measured
The primary outcome is the main question the study is designed to answer.
7 tesla MRI.
Structural morphometric analysisze of hippocampal and Papez circuit sub-regions, and detection of microinfarcts/microbleeds by 7 tesla MRI.
Measured: up to Month 18
Secondary outcomes (18)
3T MRI
Morphometry of hippocampus by 3T MRI
Measured: Baseline
3T MRI
Morphometry of hippocampus by 3T MRI
Measured: Month 12
3T MRI
Morphometry of hippocampus by 3T MRI
Measured: Month 24
3T MRI
White matter intensities assessed by 3T MRI
Measured: Baseline
3T MRI
White matter intensities assessed by 3T MRI
Measured: Month 12
3T MRI
White matter intensities assessed by 3T MRI
Measured: Month 24
7T MRI
Volumetry of the cholinergic nucleus basalis by 7T MRI
Measured: up to Month 18
CSF
CSF biomarkers
Measured: Baseline
Neuropsychological assessment
Neuropsychological assessment
Measured: Baseline
Neuropsychological assessment
Neuropsychological assessment
Measured: Month 12
Neuropsychological assessment
Neuropsychological assessment
Measured: Month 24
Clinical assessment
Clinical assessment
Measured: M0
Clinical assessment
Clinical assessment
Measured: Month 12
Clinical assessment
Clinical assessment
Measured: Month 24
Genetic markers of bvFTD
Genetic markers of bvFTD
Measured: Baseline
Blood markers
Blood markers
Measured: Baseline
Plasmatic progranulin levels
Plasmatic progranulin levels
Measured: Baseline
Regional glucose hypometabolism
Regional glucose hypometabolism assessed by FDG-PET (if performed during clinical care).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2015 (estimated)
- Study start27 Jan 2016
- Primary completion16 Oct 2023
- Study completion16 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients With Cognitive DisturbancesStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier St AnneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier St Anne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marie SARAZIN, MD, PhD, Principal investigator, Centre Hospitalier Sainte-Anne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02576821
- Sponsor's protocol ID
- D14-P010
- Acronym
- ShaTau7
- Status last verified
- Jul 2024
- First submitted
- 13 Oct 2015
- Last updated
- 12 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hippocampal Sclerosis and Amnesia Not Due to Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT02576821
- Acronym / sponsor ID
- ShaTau7 / D14-P010
- Conditions
- Patients With Cognitive Disturbances
- Keywords
- Amnesia, Alzheimer, hippocampal sclerosis, fronto-temporal lobar degeneration
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Centre Hospitalier St AnneUniversity, hospital or other
- Study start
- 27 Jan 2016 (actual)
- Primary completion
- 16 Oct 2023 (actual)
- Study completion
- 16 Oct 2023 (actual)
- First posted
- 15 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hippocampal Sclerosis (HS) leads to anterograde amnesia mimicking early Alzheimer's disease (AD) (so called HSA-nonAD). Recent studies showed that (a) the deficit of episodic memory as well as the level of hippocampal atrophy in bvFTD may be of similar severity to that observed in AD, even at initial presentation, leading to misdiagnosis in 22% of cases with post mortem diagnosis; (b) amnesia with HS due to microvascular lesion and microinfarcts can also cause impairment of episodic memory mimicking AD, without subcortical cognitive profile. Because these diseases involve distinct pathophysiological processes, they require different specific care and treatment. In consequence, it is very important to improve our knowledge about HS in order to identify its mechanism and improve the diagnosis.
Detailed description
Hippocampal sclerosis (HS) refers to neuronal cell loss and astrocytosis in subiculum and cornu ammonis subfields of the hippocampal formation unrelated to Alzheimer's disease pathology. In contrast to HS that affects younger adults with epilepsy, older individuals with HS have significant ante-mortem cognitive dysfunction but no epilepsy. Neuropathological studies demonstrated three main types of HS associated with aging: (a) HS-Ageing to refer to the disease with HS pathology in ageing individuals, observed in more than 10% of subjects aged over 85 years; (b) HS observed in the behavioural variant of frontotemporal dementia (bvFTD), HS being more frequent in tau-negative pathology, especially in FTLD-TDP. bvFTD patients may manifest severe episodic memory impairment and hippocampal atrophy; (c) HS associated with cortical or subcortical cerebral microinfarcts, which are invisible on conventional MRI. Cerebral microinfarcts are observed in 33% of elderly over 85 years in post-mortem studies.
HS leads to anterograde amnesia mimicking early Alzheimer's disease (AD) (so called HSA-nonAD). Recent studies showed that (a) the deficit of episodic memory as well as the level of hippocampal atrophy in bvFTD may be of similar severity to that observed in AD, even at initial presentation, leading to misdiagnosis in 22% of cases with post mortem diagnosis; (b) amnesia with HS due to microvascular lesion and microinfarcts can also cause impairment of episodic memory mimicking AD, without subcortical cognitive profile. Because these diseases involve distinct pathophysiological processes, they require different specific care and treatment. In consequence, it is very important to improve our knowledge about HS in order to identify its mechanism and improve the diagnosis.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Patients with Hippocampal sclerosis non AD | Other | Other: Neurological examinations, Other: Neuropsychological examinations, Other: Clinical examinations, Radiation: MRI 3T, Radiation: MRI 7TPatients with Hippocampal sclerosis non AD (n=40) |
| Patients with Alhzeimer's Disase | Other | Other: Neurological examinations, Other: Neuropsychological examinations, Other: Clinical examinations, Radiation: MRI 3T, Radiation: MRI 7TPatients with Alhzeimer's Disase (n=40) |
| Patients with DLFT | Other | Other: Neurological examinations, Other: Neuropsychological examinations, Other: Clinical examinations, Radiation: MRI 3T, Radiation: MRI 7TPatients with DLFT (n=20) |
| Patients with CBD/PSP | Other | Other: Neurological examinations, Other: Neuropsychological examinations, Other: Clinical examinations, Radiation: MRI 3T, Radiation: MRI 7TPatients with CBD/PSP (n=20) |
| Normal controls | Other | Other: Neurological examinations, Other: Neuropsychological examinations, Other: Clinical examinations, Radiation: MRI 3T, Radiation: MRI 7TNormal controls (n=20) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- General inclusion criteria
- Be older than18 years old.
- Consulting in one of the centers (patients only)
- Sufficient cognitive capacities for the realization of the clinical and neuropsychological evaluations, left to the judgement by the investigator.
- Women old enough to procreate under effective contraception
Key exclusion criteria (8 listed)
- Subject with a psychiatric evolutionary and/or badly checked pathology (left to the judgement of the investigator).
- Subject with a grave, severe or unstable pathology (left to the judgement of the investigator) the nature of which can interfere with the variables of evaluation.
- Epileptics subjects, badly tolerant MRI (1.5T, 3T or 7T), Subject presenting contraindications to the MRI (if necessary, a blood pregnancy test will be performed before 7T MRI) (Pacemaker or stimulating neurosensory or implantable defibrillator, cochlear implants, eye or cerebral ferromagnetic foreign bodies close to nervous structures, metallic prostheses, agitation of the patient : not cooperative or agitated patients, very young children, claustrophobics subjects, pregnant women, neurosurgical ventriculoperitoneal shunt valves, brace)
- Known or supposed histories (< or = 5 years) of severe alcoholism or misuse of drugs
- Vascular, inflammatory or expansive, visible lesion in the MRI which can interfere on the criteria of diagnosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neurological examinations | Other | Normal controls, Patients with Alhzeimer's Disase, Patients with CBD/PSP, Patients with DLFT, Patients with Hippocampal sclerosis non AD |
| Neuropsychological examinations | Other | Normal controls, Patients with Alhzeimer's Disase, Patients with CBD/PSP, Patients with DLFT, Patients with Hippocampal sclerosis non AD |
| Clinical examinations | Other | Normal controls, Patients with Alhzeimer's Disase, Patients with CBD/PSP, Patients with DLFT, Patients with Hippocampal sclerosis non AD |
| MRI 3T | Radiation | Normal controls, Patients with Alhzeimer's Disase, Patients with CBD/PSP, Patients with DLFT, Patients with Hippocampal sclerosis non AD |
| MRI 7T | Radiation | Normal controls, Patients with Alhzeimer's Disase, Patients with CBD/PSP, Patients with DLFT, Patients with Hippocampal sclerosis non AD |
Primary outcome
7 tesla MRI.
Time frame: up to Month 18
Structural morphometric analysisze of hippocampal and Papez circuit sub-regions, and detection of microinfarcts/microbleeds by 7 tesla MRI.
18 secondary outcomes
3T MRI
Time frame: Baseline
3T MRI
Time frame: Month 12
3T MRI
Time frame: Month 24
3T MRI
Time frame: Baseline
3T MRI
Time frame: Month 12
3T MRI
Time frame: Month 24
7T MRI
Time frame: up to Month 18
CSF
Time frame: Baseline
Neuropsychological assessment
Time frame: Baseline
Neuropsychological assessment
Time frame: Month 12
Neuropsychological assessment
Time frame: Month 24
Clinical assessment
Time frame: M0
Clinical assessment
Time frame: Month 12
Clinical assessment
Time frame: Month 24
Genetic markers of bvFTD
Time frame: Baseline
Blood markers
Time frame: Baseline
Plasmatic progranulin levels
Time frame: Baseline
Regional glucose hypometabolism
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marie SARAZIN, MD, PhD principal investigator
Centre Hospitalier Sainte-Anne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neurological examinations, Neuropsychological examinations and Clinical examinations in people with Patients With Cognitive Disturbances, run by Centre Hospitalier St Anne at 1 site in France.
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 32 inclusion and 8 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 12 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
7 tesla MRI. (time frame: up to Month 18). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jul 2024.