NCT02590276

Brief Summary

The project focuses on C9orf72, the most frequent genetic form of frontotemporal dementias (FTD, or frontotemporal lobar degeneration, FTLD) and amyotrophic lateral sclerosis (ALS). FTD is the second commonest cause of degenerative dementia in presenium after Alzheimer's disease. Behavioural and cognitive impairments progressively lead to dementia. ALS produces progressive muscle weakness leading to the death in 2 to 4 years. Since 2006, major discoveries have linked FTLD and ALS:

  1. 1.TDP-43 aggregates in neurons and
  2. 2.C9orf72 mutations is a major genetic cause in both disorders.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Oct 2015

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 5, 2015

Completed
3 days until next milestone

Study Start

First participant enrolled

October 8, 2015

Completed
21 days until next milestone

First Posted

Study publicly available on registry

October 29, 2015

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 27, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 27, 2020

Completed
Last Updated

January 20, 2021

Status Verified

August 1, 2016

Enrollment Period

5.1 years

First QC Date

October 5, 2015

Last Update Submit

January 15, 2021

Conditions

Frontotemporal Lobar DegenerationAmyotrophic Lateral Sclerosis

Keywords

frontotemporal DementiaAmyotrophic lateral sclerosisBiomarkersbrain Imaging PET

Outcome Measures

Primary Outcomes (3)

  • Change in behavioral assessment (20 scales)

    at baseline, 16 weeks and 32weeks

  • Change in MRI morphological criteria

    at baseline, 16 weeks and 32weeks

  • Change in cerebral perfusion by SPECT / PET

    at baseline, 16 weeks and 32weeks

Secondary Outcomes (1)

  • correlations between behavioral assessment, MRI morphological criteria, Cerebral perfusion and metabolism by SPECT / PET and transcriptome analysis

    32 weeks

Study Arms (1)

Evaluation

EXPERIMENTAL

Characterization

Behavioral: characterization

Interventions

characterizationBEHAVIORAL
Evaluation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18
  • Signed informed consent for genetic and clinical study
  • To be carrier of a C9ORF72 mutation - Diagnosis criteria of FTD or ALS
  • To be French-speaking
  • To be affiliated to the social security scheme
  • Absence of another intercurrent neurological pathology (vascular cerebral accident, tumor, etc.....)
  • Age ≥ 18
  • To be first degree relative of a person carrying a C9ORF72 mutation OR first degree relative of FTD or ALS deceased patient whose C9ORF72 mutation as been identified in the family
  • Signed informed consent for genetic and clinical study
  • To be French-speaking
  • To be affiliated to the social security scheme
  • Absence of proven neurologic disorders or an intercurrent neurological pathology (vascular cerebral accident, tumor, etc.....)

You may not qualify if:

  • Contra-indication to perform a brain MRI (wearing of pacemaker, cardiac valve or incompatible vascular MRI surgical equipment , neurosurgery or surgery vascular equipment, surgical equipment likely to concentrate the radio frequency field, intra ocular or intra cerebral metal foreign body, claustrophobia, wearing a non-compliant radio intrauterine device ),
  • Inability to lie one hour without moving
  • PET-FDG contra-indication
  • Breastfeeding and pregnant women
  • Human chorionic gonadotrophin (Bétâ-HCG) positive determination or Positive urine pregnancy test for women of childbearing age
  • Clinical proven signs of FTD, language disorder, praxis disorder, mnemic, of parkinson's syndrome or amyotrophic lateral sclerosis.
  • Counter-indication to perform a brain MRI (wearing of pacemaker, cardiac valve or incompatible vascular MRI surgical equipment , neurosurgery or surgery vascular equipment, surgical equipment likely to concentrate the radio frequency field, intra ocular or intra cerebral metal foreign body, claustrophobia, wearing a non-compliant radio intrauterine device )
  • Severe chronic alcoholism
  • PET-FDG contre-indication
  • Inability to lie one hour without moving
  • Bétâ-HCG positive determination or Positive urine pregnancy test for women of childbearing age

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Groupe Hospitalier Pitié-Salpêtrière - Charles Foix

Paris, 75013, France

Location

Related Publications (6)

  • Saracino D, Cipriano L, Houot M, Querin G, Rinaldi D, Rametti-Lacroux A, Wallon D, Gerardin E, Couratier P, Boncoeur MP, Lebouvier T; PREV-DEMALS and STRATALS study groups; Colliot O, Pradat PF, Migliaccio R, Le Ber I. Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease. Alzheimers Dement. 2025 Dec;21(12):e70902. doi: 10.1002/alz.70902.

    PMID: 41366786DERIVED

  • 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.

    PMID: 34349004DERIVED

  • Kmetzsch V, Anquetil V, Saracino D, Rinaldi D, Camuzat A, Gareau T, Jornea L, Forlani S, Couratier P, Wallon D, Pasquier F, Robil N, de la Grange P, Moszer I, Le Ber I, Colliot O, Becker E; PREV-DEMALS study group. Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2021 May;92(5):485-493. doi: 10.1136/jnnp-2020-324647. Epub 2020 Nov 25.

    PMID: 33239440DERIVED

  • Querin G, Bede P, El Mendili MM, Li M, Pelegrini-Issac M, Rinaldi D, Catala M, Saracino D, Salachas F, Camuzat A, Marchand-Pauvert V, Cohen-Adad J, Colliot O, Le Ber I, Pradat PF; Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis Study Group. Presymptomatic spinal cord pathology in c9orf72 mutation carriers: A longitudinal neuroimaging study. Ann Neurol. 2019 Aug;86(2):158-167. doi: 10.1002/ana.25520. Epub 2019 Jun 27.

    PMID: 31177556DERIVED

  • Wen J, Zhang H, Alexander DC, Durrleman S, Routier A, Rinaldi D, Houot M, Couratier P, Hannequin D, Pasquier F, Zhang J, Colliot O, Le Ber I, Bertrand A; Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis (PREV-DEMALS) Study Group. Neurite density is reduced in the presymptomatic phase of C9orf72 disease. J Neurol Neurosurg Psychiatry. 2019 Apr;90(4):387-394. doi: 10.1136/jnnp-2018-318994. Epub 2018 Oct 24.

    PMID: 30355607DERIVED

  • Bertrand A, Wen J, Rinaldi D, Houot M, Sayah S, Camuzat A, Fournier C, Fontanella S, Routier A, Couratier P, Pasquier F, Habert MO, Hannequin D, Martinaud O, Caroppo P, Levy R, Dubois B, Brice A, Durrleman S, Colliot O, Le Ber I; Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis (PREV-DEMALS) Study Group. Early Cognitive, Structural, and Microstructural Changes in Presymptomatic C9orf72 Carriers Younger Than 40 Years. JAMA Neurol. 2018 Feb 1;75(2):236-245. doi: 10.1001/jamaneurol.2017.4266.

    PMID: 29197216DERIVED

MeSH Terms

Conditions

Frontotemporal Lobar DegenerationAmyotrophic Lateral SclerosisFrontotemporal Dementia

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTDP-43 ProteinopathiesNeurodegenerative DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesNeurocognitive DisordersMental DisordersSpinal Cord DiseasesMotor Neuron DiseaseNeuromuscular Diseases

Study Officials

  • LE BER Isabelle, MD, PhD

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 5, 2015

First Posted

October 29, 2015

Study Start

October 8, 2015

Primary Completion

October 27, 2020

Study Completion

October 27, 2020

Last Updated

January 20, 2021

Record last verified: 2016-08

Locations

FR(1)