NCT02590276: PREV-DEMALS

Predict to Prevent Frontotemporal Lobar Degeneration (FDT) and Amyotrophic Lateral Sclerosis (ALS)

Completed NA Last updated 20 January 2021

What this trial tests

NA trial testing characterization in Frontotemporal Lobar Degeneration in 100 participants. Completed in 27 October 2020.

Timeline

8 October 2015

Primary endpoint
27 October 2020

27 October 2020

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	100
Start date	8 October 2015
Primary completion	27 October 2020
Estimated completion	27 October 2020
Sites	1 location across France

Drugs / interventions tested

• characterization

Conditions studied

• Frontotemporal Lobar Degeneration — all drugs for Frontotemporal Lobar Degeneration →
• Amyotrophic Lateral Sclerosis — all drugs for Amyotrophic Lateral Sclerosis →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Frontotemporal Lobar Degeneration or Amyotrophic Lateral Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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

Two major pathological subtypes are now defined in FTD, FTD-TDP and FTD-TAU. C9orf72 mutations (associated to FTD-TDP) are the most frequent genetic causes of FTD (15%), FTD-ALS (65%) and ALS (40%).

FTD is difficult at an early stage; and no clinical, biological or imaging features can predict the underlying pathology in living patients. Therapeutic perspectives emerged against tau aggregation, progranulin deficit and C9orf72 expansion (antisense). Presymptomatic carriers of genetic FTD would benefit, before onset of symptoms, from these therapeutic that would delay or prevent the disease. At this step, it becomes crucial to develop markers to know how many years before symptoms, does the pathological progress begin, to treat the patients at the most early 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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Early Cognitive, Structural, and Microstructural Changes in Presymptomatic C9orf72 Carriers Younger Than 40 Years.
   Bertrand A, Wen J, Rinaldi D, Houot M, et al · · 2018 · cited 120× · PMID 29197216 · DOI 10.1001/jamaneurol.2017.4266
2. Neurite density is reduced in the presymptomatic phase of <i>C9orf72</i> disease.
   Wen J, Zhang H, Alexander DC, Durrleman S, et al · · 2019 · cited 56× · PMID 30355607 · DOI 10.1136/jnnp-2018-318994
3. Plasma NfL levels and longitudinal change rates in <i>C9orf72</i> and <i>GRN</i>-associated diseases: from tailored references to clinical applications.
   Saracino D, Dorgham K, Camuzat A, Rinaldi D, et al · · 2021 · cited 47× · PMID 34349004 · DOI 10.1136/jnnp-2021-326914
4. Plasma microRNA signature in presymptomatic and symptomatic subjects with <i>C9orf72</i>-associated frontotemporal dementia and amyotrophic lateral sclerosis.
   Kmetzsch V, Anquetil V, Saracino D, Rinaldi D, et al · · 2021 · cited 32× · PMID 33239440 · DOI 10.1136/jnnp-2020-324647
5. The Advent of Omics Sciences in Clinical Trials of Motor Neuron Diseases.
   Ruffo P, Cavallaro S, Conforti FL. · · 2022 · cited 8× · PMID 35629180 · DOI 10.3390/jpm12050758
6. Quantifying multimodal longitudinal brain changes in presymptomatic C9orf72 disease.
   Saracino D, Cipriano L, Houot M, Querin G, et al · · 2025 · cited 1× · PMID 41366786 · DOI 10.1002/alz.70902
7. Visual Interpretation of Brain Hypometabolisms Related to Neurological Long COVID: A French Multicentric Experience
   Verger A, Kas A, Dudouet P, Goehringer F, et al · · 2021 · DOI 10.21203/rs.3.rs-1159513/v1