Expression Profile Study of Macrophages From Patients Affected by ALS or Other Related Motor Impairments (Mac2ALS)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04816227 |
|
Recruitment Status :
Recruiting
First Posted : March 25, 2021
Last Update Posted : May 25, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease |
|---|
| Amyotrophic Lateral Sclerosis |
Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease in adults affecting upper and lower motor neurons resulting in progressive muscle atrophy and paralysis of the patients within 2 to 5 years. The majority of ALS cases are sporadic (SALS), 5 to 10% are familial forms (FALS). In France, the most frequent mutation is an intronic hexanucleotide expansion in the C9orf72 gene, representing 46% of FALS followed by mutations in the first discovered ALS gene, SOD1 accounting for around 10% of FALS. Using mutant SOD1 ALS mouse models, the investigators and others have shown that motor neurons degenerated through a non-cell autonomous mechanism involving microglial cells. Microglial cells are the macrophages of the central nervous system (CNS) capable of producing neurotrophic or neurotoxic factors. Microglial cells are part of the myeloid lineage like macrophages at the periphery, however these two cell types have different developmental origins and are in different environments. Spinal motor neurons are particular neurons since their cell body is in the CNS, and therefore surrounded by microglial cells, while their axon extends at the periphery and is therefore in contact with peripheral macrophages. The investigators have shown that (i) peripheral macrophages in affected peripheral nerves of ALS mouse models and ALS patient post-mortem tissues were activated, (ii) in ALS mouse models, both microglial cells but also peripheral macrophages participated in disease progression and (iii) peripheral macrophages were able to influence microglial cell reactivity.
The working hypothesis is that peripheral macrophages are themselves (and not just microglial cells) involved in ALS and with this project the investigators want to compare macrophages from ALS patients and controls using macrophages derived from blood monocytes. The aim is to analyze the macrophage transcriptome and protein markers of Amyotrophic Lateral Sclerosis (ALS) patients compared to controls (non-affected individuals, patients with other motor impairments) and asymptomatic ALS gene carriers, to find new pathways to target and disease biomarkers.
| Study Type : | Observational |
| Estimated Enrollment : | 180 participants |
| Observational Model: | Case-Control |
| Time Perspective: | Prospective |
| Official Title: | Expression Profile Study of Macrophages From Patients Affected by Amyotrophic Lateral Sclerosis (ALS) or Other Related Motor Impairments |
| Actual Study Start Date : | September 29, 2021 |
| Estimated Primary Completion Date : | October 30, 2026 |
| Estimated Study Completion Date : | October 30, 2027 |
| Group/Cohort |
|---|
|
Amyotrophic Lateral Sclerosis (ALS)
Blood draw
|
|
asymptomatic carriers of ALS mutations
Blood draw
|
|
patients with motor impairment other than ALS
Blood draw
|
|
healthy controls
Blood draw
|
- Measure of transcriptome differences between the ALS group and the 3 other groups of participants. [ Time Frame: 5 years ]Will be considered different modulation superior or equal to 1.5 fold with a statistical value of p<0.05.
Biospecimen Retention: Samples With DNA
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
Group 1: Be affected by Amyotrophic Lateral Sclerosis (ALS) definite, probable or possible (El Escorial criteria) sporadic SALS (no known history in the family) or familial FALS (at least one other member of the family affected)
Group 2: Be a carrier of a known mutation causing ALS and be asymptomatic
Group 3: Have a motor impairment related to ALS including the following pathologies: Motor neuropathy, myopathy, Myositis, Spastic paraplegia, Cram / fasciculation syndrome, Chronic inflammatory polyradiculitis, somatization disorder, Anterior spinal artery syndrome, encephalitis, myelitis, Peroneal neuropathy, cervical myelopathy with radiculopathy, spinocerebellar ataxia, Kennedy disease, Spinal atrophy, Hereditary distal motor neuropathy.
Group 4: Healthy control
Inclusion Criteria:
- Agree to participate in this research and have signed an informed consent
- Be able to understand the objectives and procedures of the study
- Be affiliated to French social security or equivalent
-
Meet one of the criteria below:
(i) Be affected by Amyotrophic Lateral Sclerosis (ALS) definite, probable or possible (El Escorial criteria) sporadic SALS (no known history in the family) or familial FALS (at least one other member of the family affected), (ii) not being affected by ALS but having a close relative who has or has been diagnosed with ALS and has or is a carrier of a known mutation causing ALS and has consented to a genetic analysis, (iii) Have a motor impairment including the following pathologies: Motor neuropathy, myopathy, Myositis, Spastic paraplegia, Cram / fasciculation syndrome, Chronic inflammatory polyradiculitis, somatization disorder, Anterior spinal artery syndrome, encephalitis, myelitis, Peroneal neuropathy, cervical myelopathy with radiculopathy, spinocerebellar ataxia, Kennedy disease, Spinal atrophy, Hereditary distal motor neuropathy.
(iv) be accompanying a person with ALS or other motor impairment that is followed by one of the doctors from the ALS referral center at the Pitié-Salpêtrière hospital or by a neurologist from the neurophysiology department at the Pitié-Salpêtrière hospital.
Exclusion Criteria:
- Be subjected to a legal protection measure (safeguard of justice, curatorship or guardianship)
- Refusing to participate in the study
- Whose condition, in the opinion of the doctor, is incompatible with blood draw or participation in research
- Being pregnant or breastfeeding
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04816227
| Contact: François SALACHAS, MD | +331 42 16 24 72 | nathalie.cormand@aphp.fr | |
| Contact: Severine BOILLEE, PhD |
| France | |
| Département de Neurologie, Hôpital de la Pitié-Salpêtrière | Recruiting |
| Paris, France, 75013 | |
| Contact: François Salachas, MD | |
| Study Director: | François SALACHAS, MD | APHP, Hôpital de la Salpêtrière, INSERM U1127, ICM |
| Responsible Party: | Institut National de la Santé Et de la Recherche Médicale, France |
| ClinicalTrials.gov Identifier: | NCT04816227 |
| Other Study ID Numbers: |
C20-55 2020-A03348-31 ( Registry Identifier: ID RCB ) |
| First Posted: | March 25, 2021 Key Record Dates |
| Last Update Posted: | May 25, 2022 |
| Last Verified: | May 2022 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases |
Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |