To study the role of brain metabolites and macromolecules in relationship to pathogenesis, structural brain changes and clinical phenotype of ALS. This will reveal underlying molecular mechanisms of pathogenesis, structural brain changes and…
ID
Source
Brief title
Condition
- Neuromuscular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters are the level of brain metabolites as obtained with
1H-MRS and 31P-MRS that should discriminate between ALS patients, familiar
persons and healthy persons.
• Quantification of metabolites related to energy metabolism, such as Creatine,
Glutamate, Glutamine (1H-MRS) and phosphocreatine, ATP and ADP (31P-MRS).
• Quantification of metabolite levels related to neuronal/glial loss, such as
N-Acetylaspartic acid, Choline, Creatine and Myo-Inositol (1H MRS).
• Relation of these metabolite levels in regions with cortical thickness.
• Quantification of neurotransmitter levels such as GABA (inhibitory
neurotransmission) and Glutamate and Glutamine (excitatory neurotransmission)
(1H MRS) and their relation with cartical thinning and clinical phenotype.
• The relation of these metabolites levels to each other to discover a pattern
of metabolic involvement in ALS.
Secondary outcome
• Clinical parameters including age, gender, age at onset of disease, site of
onset, El Escorial criteria, disease severity (as measured by ALSFRS
questionnaire), disease duration and progression rate, and presence of
cognitive impairment (as measured by ECAS, as explained in the next section) in
relation with brain metabolites.
Background summary
Pathological studies as well as imaging studies have shown alterations in the
brain of patients with amyotrophic lateral sclerosis (ALS). Distinct molecular
mechanisms play a role in the pathogenesis of ALS. Using Magnetic Resonance
Spectroscopy (MRS) techniques, the metabolites, neurotransmitters and
macromolecules involved in those molecular mechanisms can be quantified. This
opens opportunities to study the role of brain metabolites in ALS pathogenesis
in vivo in (presymptomatic) ALS patients. This will result in new knowledge
about pathophysiology of ALS and might offer new targets for future therapies.
Study objective
To study the role of brain metabolites and macromolecules in relationship to
pathogenesis, structural brain changes and clinical phenotype of ALS. This will
reveal underlying molecular mechanisms of pathogenesis, structural brain
changes and clinical phenotype in vivo.
Study design
Observational case-control study
Intervention
All subjects will receive a MRI scan with a ttotal duration of approximately 60
minutes including 10 minutes for preparation and planning. MRI protocol
consists of a T1 weighted 3D anatomical scan, 1H-MRS with water and fat
suppression and 31P-MRS.
Study burden and risks
Participants will undergo a clinical assessment and MRI examination at the
University Medical Center (UMC) Utrecht. Standardized 7T MRI checklists will be
used to ensure MRI safety. The burden for the patient includes the time the
patient will spend for making the 7T MRI scans and travel time to the hospital.
Patients will be compensated for travel costs made for the visits to the
hospital for the 7T MRI examination. There are no direct benefits for the
individual participant. Information acquired by this research project provides
new insights in molecular pathways that might become involved in ALS.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
1. Subjects
a. ALS patients: definite, probable, probable-laboratory supported or possible ALS according to the revised El Escorial criteria (Brooks 2000);
- familar ALS is defined only if there is a family history of ALS.
b. Healthy control subjects without ALS: including family members of ALS patients with and without an established mutation, without any sign of ALS.
2. Age 18 - 80 years (inclusive)
3. Capable of thoroughly understanding the study information given; has signed the informed consent.
4. Capable of climbing up the stairs, so the patient is able to climb up the MRI table
Exclusion criteria
• Tracheostomy, tracheostomal ventilation of any type, (non)-invasive ventilation.
• Any history or presence of brain injury, epilepsy, psychiatric illness and other cerebral disease (not related to ALS).
• Any intoxication or medication known to have an association with motor neuron dysfunction, which might confound or obscure the diagnosis of motor neuron disease.
• Presence of pronounced swallowing disorders or orthopnoea (which make it dangerous to lie supine in the MRI scanner).
• Contra-indications to MRI scanning according to hospitals 7T MRI screening guideline of the UMC Utrecht.
• Pregnancy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL55287.041.15 |