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Frontotemporal Lobar DegenerationPredict-PGRNNCT04014673

Natural History Characterization in Symptomatic and Asymptomatic Progranuline Gene Mutation Carriers

A study testing Behavioral : Characterization in people with Frontotemporal Lobar Degeneration, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.

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 purpose of this study is to investigate whether cognitive deficits, structural and functional changes can be detected before symptom onset in presymptomatic progranuline mutation carriers. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Frontotemporal Lobar Degeneration
What is being tested?
Behavioral : Characterization
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
2 sitesFrance
Study dates
19 Jan 2010to 6 Oct 2022
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

  • Age ≥ 18
  • Signed informed consent for genetic and clinical study
  • To be carrier of a PGRN mutation - Diagnosis criteria of FTD
  • To be affiliated to the social security scheme
  • Age ≥ 18
  • To be first degree relative of a person carrying a PGRN mutation or first degree relative of FTD deceased patient whose PGRN mutation as been identified in the family
  • Signed informed consent for genetic and clinical study
  • To be affiliated to the social security scheme

Who cannot join

  • Presence of one exclusion criteria from Diagnosis criteria of FTD. - Participation to another therapeutic trial. - Contra-indication to perform a brain MRI and/or PET-FDG
  • Inability to lie one hour without moving
  • Breastfeeding and pregnant women
  • Presence of another intercurrent neurological pathology (vascular cerebral accident, tumor, etc.....)
  • Presence of neurological or neurodegenerative disease
  • Clinical proven signs of FTD, language disorder, praxis disorder, mnemic, of parkinson's syndrome or amyotrophic lateral sclerosis
Show all 10Show fewer
  • Contra-indication to perform a brain MRI and/or PET-FDG
  • Inability to lie one hour without moving
  • Breastfeeding and pregnant women
  • Severe vascular lesion , tumor or infectious brain imaging if an MRI was done previously

Trial locations and contacts

2 sites in 1 country.

France2 sites
  • Groupe Hospitalier Pitié-Salpêtrière - Charles Foix

    Paris, 75013

  • Pitié Salpetriere Hospital

    Paris, 75013

Other trials in France

About this study

The purpose of this study is to investigate whether cognitive deficits, structural and functional changes can be detected before symptom onset in presymptomatic progranuline mutation carriers. The main objectives of the project are to identify novel cognitive, brain imaging markers and peripheral biomarkers for early diagnosis of FTLD, and to follow disease progression.

Read the detailed description

The project focuses on the progranulin (PGRN) gene mutation, one of the most frequent genetic forms of frontotemporal dementias (FTD, or frontotemporal lobar degeneration, FTLD). FTD is the second commonest cause of degenerative dementia in presenium after Alzheimer's disease. Behavioral and cognitive impairments progressively lead to dementia. Two major pathological subtypes are now defined in FTD, FTD-TDP and FTD-TAU.

FTD is difficult to detect at an early stage, and no clinical, biological or imaging features can predict the underlying pathology in living patients. Therapeutic perspectives have emerged against tau aggregation, PGRN deficit and C9orf72 expansion. Presymptomatic carriers of genetic FTD would benefit, before onset of symptoms, from these therapeutics that would delay or prevent the disease. At this step, it becomes crucial to develop markers to know how many years before symptoms, the pathological process begins, to treat the patients at the earliest stage of the disease. Markers are also needed to predict the pathology (FTD-TDP/FTD-tau) in patients that will be eligible for trials targeting specific pathological lesion. The main objectives of the project are to identify novel cognitive, brain imaging markers and peripheral biomarkers for early diagnosis of FTLD, and to follow disease progression. Ninety participants including 8 patients and 82 'at-risk' individuals will be recruited and evaluated by clinical partners of the project (Paris, Lille, Rouen, Toulouse, Saint-Etienne, Marseille, Nantes). 'At-risk individuals' are the first- degree relatives of PGRN patients, who have a high a risk (50%) to carry the mutation.

Brain structural changes will be evaluated by voxel-based morphometry (SPM12 software) to assess global brain atrophy in one with the evaluation of atypical shape patterns such as cortical thickness (Freesurfer software) and the study of the cortical sulci (BrainVISA/Morphologist software).

Fluoro Deoxy DGlucose-Positron Emission Tomography (FDG-PET) will allow the identification of brain metabolic markers. Then voxel-based methods using Statistical Parametric Mapping software will be applied to compare different groups or analyze correlations between brain metabolism and cognitive deficits.

The identification of peripheral biomarkers of disease onset and disease progression will take advantage from RNA sequencing, in order to study gene expression and RNA splicing alterations in lymphocytes of patients and 'at risk individuals'.

Being tested
Behavioral : Characterization
Keywords
Frontotemporal Dementia,, biomarkers,, brain Imaging PET
Medical subject headings
Frontotemporal Lobar Degeneration, Frontotemporal Dementia

What participants receive

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

  • Behavioral : CharacterizationBehavioural

    Behavioral scales and neuropsychological tests; MRI, SPECT/PET

Study groups in NCT04014673
Study groupRoleWhat they receive
Patients with a PGRN gene mutationOtherSymptomatic patients with a PGRN gene mutation
Receives: Behavioral: Behavioral : Characterization
Presymptomatic individualsOtherAsymptomatic 'At-risk' individuals with a PGRN gene mutation
Receives: Behavioral: Behavioral : Characterization
healthy volunteersOther'At-risk' individuals without a PGRN gene mutation
Receives: Behavioral: Behavioral : Characterization

What is being measured

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

  1. Rate of change of Frontal Assessment Battery score (/18)

    Executive functions changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  2. Rate of change of Trail Making Test B-A time (seconds)

    Cognitive flexibility changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  3. Rate of change of Ekman's faces test score (/35)

    Emotional assessment changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  4. Rate of change of Faux-pas test score (/35)

    Social cognition changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  5. Rate of change of Digit span score

    Short-term memory changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  6. Rate of change of Free and Cued Selective Reminding test, total recall score (/48)

    Long-term memory changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  7. Rate of change of Boston Naming test score (/34)

    Language changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  8. Rate of change of Gestural Praxis battery score (/168)

    Gestural praxis changes over time (rate of change in neuropsychological test)

    Measured: at baseline 0 Months,at 42 Months, at 72 Months

  9. Rate of change of Neuropsychiatric Inventory score (/144)

    Behavioral changes over time (rate of change in neuropsychological questionnaire)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  10. Rate of change of Apathy Evaluation Scale score (/42)

    Apathy changes over time (rate of change in neuropsychological questionnaire)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  11. Change in MRI morphological criteria (brain atrophy by voxel-based morphometry)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  12. Change in cerebral metabolism by PET (metabolic markers by Fluoro-DeoxyDGlucose-Positron Emission Tomography (FDG-PET))

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

Secondary outcomes (2)
  1. Correlations between cognitive and behavioral scores, MRI morphological criteria, cerebral metabolism by FDG-PET and transcriptome analysis in presymptomatic subjects and in symptomatic patients at early disease stage

    Voxel-based methods using Statistical Parametric Mapping software will be applied to compare different groups or analyze correlations between brain atrophy/metabolism and cognitive deficits.

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

  2. Differences in transcriptome analysis between symptomatic patients, asymptomatic carriers and controls.

    Study gene expression and RNA splicing alterations in lymphocytes (RNA sequencing)

    Measured: at baseline 0 Months,at 42 Months,at 72 Months

Timeline

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

  1. First posted10 Jul 2019
  2. Study start19 Jan 2010
  3. Primary completion6 Oct 2022
  4. Study completion6 Oct 2022

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04014673
Sponsor's protocol ID
P071229
Acronym
Predict-PGRN
Status last verified
Dec 2024
First submitted
15 Apr 2019
Last updated
24 Dec 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Caroppo P, Habert MO, Durrleman S, Funkiewiez A, Perlbarg V, Hahn V, Bertin H, Gaubert M, Routier A, Hannequin D, Deramecourt V, Pasquier F, Rivaud-Pechoux S, Vercelletto M, Edouart G, Valabregue R, Lejeune P, Didic M, Corvol JC, Benali H, Lehericy S, Dubois B, Colliot O, Brice A, Le Ber I; Predict-PGRN study group. Lateral Temporal Lobe: An Early Imaging Marker of the Presymptomatic GRN Disease? J Alzheimers Dis. 2015;47(3):751-9. doi: 10.3233/JAD-150270.

    PubMed 26401709
  • Saracino D, Sellami L, Boniface H, Houot M, Pelegrini-Issac M, Funkiewiez A, Rinaldi D, Locatelli M, Azuar C, Causse-Lemercier V, Jaillard A, Pasquier F, Chastan M, Wallon D, Hitzel A, Pariente J, Pallardy A, Boutoleau-Bretonniere C, Guedj E, Didic M, Migliaccio R, Kas A, Habert MO, Le Ber I; Predict-PGRN. Brain Metabolic Profile in Presymptomatic GRN Carriers Throughout a 5-Year Follow-up. Neurology. 2023 Jan 24;100(4):e396-e407. doi: 10.1212/WNL.0000000000201439. Epub 2022 Oct 18.

    PubMed 36257714
  • Saracino D, Dorgham K, Camuzat A, Rinaldi D, Rametti-Lacroux A, Houot M, Clot F, Martin-Hardy P, Jornea L, Azuar C, Migliaccio R, Pasquier F, Couratier P, Auriacombe S, Sauvee M, Boutoleau-Bretonniere C, Pariente J, Didic M, Hannequin D, Wallon D; French Research Network on FTD/FTD-ALS; PREV-DEMALS and Predict-PGRN study groups; Colliot O, Dubois B, Brice A, Levy R, Forlani S, Le Ber I. Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1278-1288. doi: 10.1136/jnnp-2021-326914. Epub 2021 Aug 4.

    PubMed 34349004

Questions about this trial

What is this clinical trial studying?

A study testing Behavioral : Characterization in people with Frontotemporal Lobar Degeneration, run by Assistance Publique - Hôpitaux de Paris at 2 sites 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 8 inclusion and 10 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 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Rate of change of Frontal Assessment Battery score (/18) (time frame: at baseline 0 Months,at 42 Months,at 72 Months). The study lists 12 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 NCT04014673, which also lists 3 linked publications.

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 24 Dec 2024.

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