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, 2H-MRS, that should discriminate between ALS patients, asymptomatic
family members of patients with ALS and healthy controls. This will be used to
derive the main outcome:
-TCA-cycle rate.
Main parameters from MRS.
- Glutamate, glutamine, glucose, lactate,
Main parameters from blood.
- Glucose, lactate, % deuterium enrichment.
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 in relation with brain metabolites.
Other MRS parameters
-N-acetyl aspartate (NAA), choline (Cho), creatine (Cr)
The primary outcome measure will be related to secondary parameters as well as
parameters as acquired in earlier studies, mainly the anatomical MRI data as
acquired in Imaging MND 11-552. e.g. cortical thinning.
Background summary
Pathological studies and 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. Magnetic Resonance
Spectroscopic imaging (MRSI) techniques can quantify the metabolites and
neurotransmitters involved in those molecular mechanisms. 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
the pathophysiology of ALS and might offer new targets for future therapies.
The principle of this study has been proven in its predecessor: "In vivo
imaging of brain metabolism in ALS". The results of this study (awaiting
publication) have shown numerous aspects of metabolic changes in ALS. With this
new study design, we want to use new MR techniques to look further into the
aspects of brain metabolism which have shown changes and also into new aspects.
One of these aspects is the glucose metabolism, deuterium-glucose can be
dynamically followed and its metabolites quantified and as such give
information about this process in vivo.
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
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,
placement of an IV drip and be in fasting state for 6hrs prior to the MR-scan.
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.
a. ALS patients: definite, probable, probable-laboratory supported or possible
ALS according to the revised El Escorial criteria (Brooks 2000); only if ALS
patients have a family history of ALS, this will be defined as fALS.
b. Healthy control subjects without ALS: including family members of ALS
patients with or without an established mutation (i.e. we will not select them
based on any knowledge about a mutation they might carry), 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.
5. Willing and able to lie in an MRI scanner uninterrupted for 90 minutes.
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 and/or to drink 2H-glucose).
• Diabetes mellitus
• Contra-indications to MRI scanning according to hospitals 7T MRI screening
guideline of the UMC Utrecht.
• Pregnancy
• Any intoxication or medication that could influence the cerebral glucose
metabolism as judged by the researcher
Design
Recruitment
Medical products/devices used
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 | NL85201.041.23 |